Modified silk fibroin and medical uses thereof

Abstract

The disclosure relates to methods of treatment or prevention of a disorder, disease, or condition in a subject, method comprising administering to the subject a composition comprising fibroin fragments, e.g., silk fibroin derived peptide compositions.

Description

[0001]Modified Silk Fibroin and Medical Uses Thereof CROSS REFERENCE TO RELATED APPLICATIONS The present application claims priority to and the benefit of United States patent application Nos.63 / 580,984, filed September 6, 2023, 63 / 656,317, filed on June 5, 2024 and 63 / 671,527, filed July 15, 2024. All forgoing applications are incorporated herein by reference in their entireties for any and all purposes. FIELD The disclosure relates to methods of treatment or prevention of a disorder, disease, or condition comprising administering to the subject a composition comprising fibroin fragments, e.g., silk fibroin derived peptide compositions. BACKGROUND Silk is a natural polymer produced by a variety of insects and spiders, and comprises a filament core protein, silk fibroin, and a glue-like coating consisting of a non-filamentous protein, sericin. Silk fibers are lightweight, breathable, and hypoallergenic. SUMMARY The disclosure provides a method of treatment or prevention of a disorder, disease, or condition in a subject in need thereof, the method comprising administering to the subject a composition comprising fibroin fragments, wherein the fibroin fragments comprise a plurality of modified fibroin fragments. In some embodiments, the disease, disorder or condition is selected from Atopic Dermatitis (Eczema), Psoriasis (e.g., plaque psoriasis), Contact Dermatitis, rosacea, acne (e.g., cystic acne), Ichthyosis (e.g., ichthyosis vulgaris), inflammation, Netherton Syndrome (a genetic disorder that lead to chronic skin inflammation and increased susceptibility to an infection), Xerosis (Dry Skin), Aging Skin, impaired wound healing, Diabetic Dermopathy, Pruritus, Scleroderma, Multiple Sclerosis (MS), Bacterial and fungal Infection, abnormal scarring condition, melanoma, dysbiosis, autoimmune condition like lupus, Systemic Lupus Erythematosus, and rheumatoid arthritis. In some embodiments, the disorder, disease, or condition is an inflammatory disease, disorder or condition selected from Rheumatoid Arthritis, Inflammatory Bowel Disease, Systemic Lupus Erythematosus, Multiple Sclerosis (MS), Psoriasis, Asthma, allergic rhinitis, asthma, food allergy, and another autoimmune condition. In some embodiments, the disease, disorder or condition is selected from inflammatory bowel disease (IBD), Intestinal Permeability, Crohn's disease, ulcerative colitis, celiac disease, irritable bowel syndrome (IBS), NASH, cirrhosis, metabolic disorders, and another disease, a disorder or condition involving regulation of a gut epithelial cell. In some embodiments, the disease, disorder or condition is a neurodegenerative condition selected from Alzheimer’s Disease (AD), Multiple Sclerosis (MS), Parkinson’s Disease (PD), and Amyotrophic Lateral Sclerosis (ALS). In some embodiments, the disease, disorder or condition is a metabolic condition selected from obesity and type 2 Diabetes, and non-alcoholic fatty liver disease (NAFLD). In some embodiments, the disease, disorder or condition is a cancer. In some embodiments, the disease, disorder or condition is associated with dysregulation in a gut barrier and / or in a tight junction of the gut. In some embodiments, a fibroin fragment interacts with lipoteichoic acid, lipomannan, a TLR- 2 receptor, or a protein kinase. In some embodiments, the protein kinase is a Tyrosine-protein kinase. In some embodiments, a fibroin fragment binds to a protein disulfide isomerase (PDI), a CD44 receptor, Annexin A2, Keratin 5, Keratin 1, or Keratin 10. In some embodiments, a fibroin fragment binds to a CD44 receptor. In some embodiments, the disease, disorder, or condition is alleviated by decreasing the secretion of TNF-α and IL-6, and / or increasing secretion of IL-10. In some embodiments, the disease, disorder, or condition is alleviated by modulating Annexin A2’s role in tumor growth, immune function, neuronal protection, and / or metabolic processes. In some embodiments, the disorder, disease, or condition is alleviated by stimulating or modulating a skin barrier-specific protein in a subject in need thereof. In some embodiments, the skin barrier-specific protein is differentially regulated. In some embodiments, the skin barrier-specific protein comprises at least one of desmoplakin (DSP), cystatin A (CSTA), tumor-associated calcium signal transducer 2 (TACSTD2), biglycan (BGN), decorin (DCN) and / or epiplakin 1 (EPPK1). In some embodiments, at least one of desmoplakin (DSP), cystatin A (CSTA) and / or tumor-associated calcium signal transducer 2 (TACSTD2) is upregulated post-administration. In some embodiments, at least one of biglycan (BGN), decorin (DCN) and / or epiplakin 1 (EPPK1) is downregulated post- administration. In some embodiments, at least one of the skin barrier-specific protein is a tight junction protein. In some embodiments, a fibroin fragment binds to a skin epithelial cell and / or induces upregulation of the tight junction protein. In some embodiments, the tight junction protein is Claudin-1, occludin, or Zo1. In some embodiments, tight junction protein is Claudin-1 expressing in a human epidermal keratinocyte. In some embodiments, a claudin-1 level is promoted, increased, or restored post- administration in the epidermal keratinocyte. In some embodiments, the epidermal keratinocyte is an h-TERT immortalized keratinocyte. In some embodiments, the epidermal keratinocyte is a primary human keratinocyte. In some embodiments, a fibroin fragment promotes a growth of a normal skin microbiome and a probiotic bacteria by interacting with a receptor on a probiotic bacteria surface. In some embodiments, the probiotic bacteria is selected from Micrococcus luteus, Lactiplantibacillus plantarum, and Lacticaseibacillus rhamnosus. In some embodiments, administering the composition improves the function of a skin keratinocyte and a fibroblast. In some embodiments, administering the composition promotes skin barrier function, regulates immune responses, and / or confers pathogen bacteria colonization resistance. In some embodiments, the fibroin fragment penetrates an intact skin barrier and binds to a dermal fibroblast. In some embodiments, administering the composition induces de novo collagen synthesis, secretion and / or increases extracellular matrix deposition. In some embodiments, administering the composition induces secretion of pro-Col1A1, Col3A, and / or ɑ- SMA. In some embodiments, the fibroin fragment accelerates skin barrier regeneration by promoting expression of the tight junction protein. In some embodiments, the fibroin fragment is a keratinocyte differentiation factor (KDF) polypeptide. In some embodiments, the KDF polypeptide enhances keratinocyte differentiation and / or Filaggrin maturation. In some embodiments, the KDF polypeptide increases expression and maturation of Involucrin and / or Filaggrin A. In some embodiments, the tight junction protein is selected from Claudin-1 and Occludin. In some embodiments, the KDF polypeptide binds to a corneal keratin selected from Keratin 1 and Keratin 10. In some embodiments, the KDF polypeptide induces a switch from a basally-expressed keratin (e.g. K5, K14) to a suprabasally- expressed keratin (e.g. K1, K10). In some embodiments, the KDF polypeptide enters the skin and binds selectively to the CD44 receptor on a stratum basale cell. In some embodiments, the KDF polypeptide binds to an undifferentiated keratinocyte in the skin and accelerates keratinocyte differentiation to accelerate skin barrier regeneration. In some embodiments, the composition maintains skin extracellular matrix (ECM) homeostasis. In some embodiments, the subject in need experiences reduced erythema post-administration, decreased transepidermal water loss post- administration, a reduced eczema lesion count post-administration, reduced edema post-administration, reduced rhytids post-administration, increased skin hydration post-administration, increased skin firmness post-administration, a reduced sign of skin inflammation post-administration, and / or a reduced sign of aging skin post- administration. In some embodiments, the composition is administered in combination with vitamin C. In some embodiments, administering the composition in combination with vitamin C synergistically increases pro-Col1A1 secretion. In some embodiments, the composition is administered parenterally. In some embodiments, the composition is formulated as a topical composition. In some embodiments, the composition comprises a population of neutral fibroin fragments, a population of positively charged fibroin fragments, or a population of negatively charged fibroin fragments. In some embodiments, the silk fibroin fragments have a weight average molecular weight from about 1 kDa to about 250 kDa. In some embodiments, the composition comprises a fibroin fragment subpopulation having a weight average molecular weight selected from between about 5 kDa to about 10 kDa, between about 10 kDa to about 40 kDa, between about 40 kDa to about 70 kDa, between about 70 kDa to about 100 kDa, between about 100 kDa to about 130 kDa, between about 130 kDa to about 150 kDa, between about 150 kDa to about 180 kDa, between about 180 kDa to about 210 kDa, or between about 210 kDa to about 240 kDa. In some embodiments, the composition comprises a fibroin fragment subpopulation having a weight average molecular weight selected from between about 20 kDa to about 50 kDa, between about 50 kDa to about 80 kDa, between about 80 kDa to about 110 kDa, between about 110 kDa to about 140 kDa, between about 140 kDa to about 170 kDa, between about 170 kDa to about 200 kDa, between about 200 kDa to about 230 kDa, or between about 230 kDa to about 250 kDa. In some embodiments, the composition comprises a fibroin fragment subpopulation having a polydispersity selected from between 1 to about 3. In some embodiments, the composition comprises a fibroin fragment subpopulation having an isoelectric point selected from between about 4.4 to about 9.6. In some embodiments, the composition comprises a fibroin fragment subpopulation having a self assembly rate factor selected from between 0 to about 5. In some embodiments, the composition comprises a fibroin fragment subpopulation having a self assembly rate factor selected from between about 0.6 to about 4. In some embodiments, the composition comprises a fibroin fragment subpopulation each having a self assembly factor selected from between about 0.5 to about 0.9. In some embodiments, the composition comprises a fibroin fragment subpopulation having a self assembly rate factor selected from between about 5 to about 11. In some embodiments, the composition comprises a fibroin fragment subpopulation having an Amaxselected from between 0 to about 0.7. In some embodiments, the composition comprises a fibroin fragment subpopulation having an Amaxselected from between about 0.5 to about 0.8. In some embodiments, the composition comprises a fibroin fragment subpopulation having a t0.5(min) selected from between 0 to about 1500. In some embodiments, the composition comprises a fibroin fragment subpopulation having a t0.5(min) selected from between 0 to about 1000. In some embodiments, the modified fibroin fragments comprise one or more amino acid residue modifications selected from an asparagine to aspartic acid modification, a glutamine to glutamic acid modification, and a methionine to methionine oxide modification. In some embodiments, a plurality of modified fibroin fragments comprise one modification. In some embodiments, a plurality of modified fibroin fragments comprise two modifications. In some embodiments, a plurality of modified fibroin fragments comprise three modifications. In some embodiments, the asparagine to aspartic acid modification is at one or more positions selected from N23, N28, N108, N118, N136, N186, N200, N204, N240, N248, N68, N70, N77, N5262, N93, N132, N149, N172, N174, N202, N105, N4191. In some embodiments, the glutamine to glutamic acid modification is at one or more positions selected from Q24, Q149, Q202, Q58, Q139, Q275, Q5216, Q255, and Q125. In some embodiments, the methionine to methionine oxide modification is at the M64 position. In some embodiments, a % modification is defined as (number of modified fibroin fragments having a modification at a specific position divided by the total number of fibroin fragments which includes the specific position, modified or unmodified) x 100. In some embodiments, each modification is independently ranging in the composition between about 1% to about 99%. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutically acceptable carrier comprises or is formulated as one or more of a cosmeceutical, a suspension, an emulsion, a powder, a solution, a dispersion, or an elixir. In some embodiments, the pharmaceutically acceptable carrier comprises or is formulated as one or more of a gel, a jelly, a cream, a lotion, a foam, a slurry, an ointment, an oil, a paste, a suppository, a spray, a semisolid composition, a solid composition, a stick, or a mousse. In some embodiments, the pharmaceutically acceptable carrier comprises one or more of aliphatic oil, a fatty alcohol, a fatty acid, a glyceride, an acylglycerol, and a phospholipid. In some embodiments, the pharmaceutically acceptable carrier comprises one or more of a monoglyceride, a diglyceride, or a triglyceride. In some embodiments, the pharmaceutically acceptable carrier comprises an aqueous phase. In some embodiments, the pharmaceutically acceptable carrier comprises an oil-in-water emulsion or a water-in-oil emulsion. In some embodiments, the pharmaceutically acceptable carrier comprises one or more of a hydrocarbon oil, a fatty acid, a fatty oil, a fatty acid ester, or a cationic quaternary ammonium salt. The disclosure provides a dual syringe kit comprising a first syringe including the composition of any one of the embodiments disclosed herein comprising fibroin fragments; and a second syringe including a silk-hyaluronic acid hydrogel. In some embodiments, the first syringe comprises about 0.1 mL, about 0.2 mL, about 0.3 mL, about 0.4 mL, or about 0.5 mL of the composition. In some embodiments, the firoin fragments are formulated in an aqueous solution. In some embodiments, the firoin fragments are formulated in a gel composition. In some embodiments, the second syringe comprises about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, about 1.0 mL, about 1.2 mL, about 1.3 mL, about 1.4 mL, or about 6.5 mL of the silk-hyaluronic acid hydrogel. In some embodiments, the silk-hyaluronic acid hydrogel is crosslinked. In some embodiments, the composition and the silk- hyaluronic acid hydrogel are mixed together to form an admixture before being applied to a skin of the subject. In some embodiments, the admixture is applied to the skin of the subject using a derma roller. In some embodiments, the admixture is applied to the skin of the subject using a microchanneling technique. In some embodiments, the admixture is applied to the skin of the subject using fractional microneedle radiofrequency (RF). In some embodiments, the admixture is applied to the subject using platelet-rich plasma (PRP) therapy. The disclosure provides a method of treatment or prevention of a disorder, disease, or condition in a subject in need thereof, the method comprising administering to the subject the admixture of any one of the embodiments disclosed herein. In some embodiments, the subject in need experiences increased stimulation of collagen production post-administration, improved skin hydration post- administration, improved skin texture and elasticity post-administration, a reduction in skin redness post-administration, and / or a reduction in inflammation post- administration. The disclosure provides a method for identifying a protein, comprising employing Far Western Blot, SDS-polyacrylamide gel electrophoresis (SDS-PAGE), and / or LC / MS analysis, wherein the fibroin fragment of any one of the embodiments disclosed herein binds to the protein. In some embodiments, the fibroin fragment is a polypeptide composition derived from B. mori silk. In some embodiments, the protein is in a human tissue. In some embodiments, the human tissue is skin. In some embodiments, the protein in the human tissue is Keratin Type II Cytoskeletal 1 (KRT1), or Keratin type I cytoskeletal 10 (KRT10). BRIEF DESCRIPTION OF THE DRAWINGS The presently disclosed embodiments will be further explained with reference to the attached drawings. The drawings shown are not necessarily to scale, with emphasis instead generally being placed upon illustrating the principles of the presently disclosed embodiments. FIG.1 depicts Ion Exchange Fractionation Schemes for the isolation of the populations that constitute Low and Mid Skid silk / modified polypeptide compositions. Low and Mid Skid silk / modified polypeptide compositions contains silk / modified polypeptides that are negatively, positively charged, or neutral. Using Q anion exchange chromatography (A) these populations were isolated. FIG.2 depicts chromatogram of Low Skid silk / modified polypeptide composition loaded in a Q-Sepharose HP column (Cytiva). The flow through contains the silk / modified polypeptides that do not get captured in the column and are the depleted in negatively charged amino acids. After the column is loaded with Low or Mid Skid silk / modified polypeptide compositions and the flow through is collected, the column is washed until the UV-280 absorbance becomes less than 200 AU. The captured negatively charged silk / modified polypeptides are eluted with high salt concentration (1M NaCl) and constitute AS11 and AS22. The chromatography is performed in Tris-containing buffers but the flow through and the Q-elution were finally dialyzed in water. FIG.3 depicts Analytical Size Exclusion Chromatography of Low, Mid Skid silk / modified silk compositions and their constituent AS compositions. Average molecular weight in kDa and polydispersity measurements are shown. FIG.4A and FIG.4B depict Analytical Size Exclusion Chromatography of the Low and Mid skid silk / modified peptide compositions and their components (see table 1 for more details). FIG.4A, Molecular weight of the various Activated Silk new compositions described in this study. FIG.4B, Polydispersity (PDI) of the various Activated Silk new compositions described in this study. AS24 reconstitutes the average molecular weight and polydispersity of the Low skid silk / modified peptide composition and it consists of 50% AS12 and 50% AS22 (see Table 1 for details). AS6 reconstitutes the average molecular weight and polydispersity of the Mid skid silk / modified peptide composition and it consists of 50% AS1 and 50% AS11 (see Table 1 for details). FIG.5 depicts Isoelectric Focusing Electrophoresis of Low Skid silk / modified polypeptide compositions. Lanes 2, 7; Low Skid silk different amounts loaded. Lanes 3, 5, 8, 10; AS12 silk, different preparations different amounts loaded. Lanes 4, 6, 9, 11; AS22 silk, different preparations different amounts loaded. FIG. 6A and FIG.6B depict self-assembly reactions of the of the Low and Mid skid silk / modified peptide compositions and their components (see Table 1 for more details). Both graphs depict the kinetic parameters of gel formation during self- assembly of silk. On graph FIG.1A calculation of the three self-assembly kinetic parameters is shown, t0.5, Amax and SARF. FIGS.7A-C depict self-assembly kinetics of the Low and Mid skid silk / modified peptide compositions and their components (see table 1 for more details). FIG.7A, the Self-assembly Rate Factor shows how fast the self-assembly reaction proceeds once it is initiated and the self-assembly nuclei are organized. FIG. 7B, Maximum Gel Yield shows how dense the silk gel is after self-assembly is complete. FIG 7C, Time required for the self-assembly reaction to produce half of the maximum gel amount. FIG.8 depict the Low and Mid skid silk / modified peptide compositions and their components (see Table 1 for more details). The Self Assembly Factor reflects the average propensity of silk to self-assemble and form gels. FIG.9 is a graph of molecular weight plotted as a function of time for solubilized fibroin in 9.3 M LiBr at 100°C - 103°C FIG.10 is a graph of molecular weight plotted as a function of time for solubilized fibroin in 9.3 M LiBr at 122°C - 125°C FIG.11 is a graph illustrating percentage of amino acid modification in silk. FIGS.12A-12C are graphs illustrating percentage of amino acid modifications in Low and Mid Skid silk. FIG.12A illustrates heavy chain modifications, FIG.12B illustrates light chain modifications, and FIG.12C illustrates fibrohexamerin modifications. N are Asparagines that become aspartic acid and Q are Glutamines that become deamidated. M corresponds to Methionies that become oxidized. FIG.13A and FIG.13B are graphs illustrating percentage of amino acid modifications in Low and Mid Skid silk produced and lyophilized. FIG.13A illustrates heavy chain modifications and FIG.13B illustrates light chain modifications. N are Asparagines that become aspartic acid and Q are Glutamines that become deamidated. M corresponds to Methionies that become oxidized. FIG.14A and FIG.14B are graphs illustrating percentage of amino acid modifications in Low Skid silk produced in two different facilities. FIG.14A illustrates heavy chain modifications and FIG.14B illustrates light chain modifications. N are Asparagines that become aspartic acid and Q are Glutamines that become deamidated. M corresponds to Methionies that become oxidized. FIGS.15A-15D are graphs illustrating percentage of amino acid modifications in Mid silk produced in Skid and Benchtop scale. N are Asparagines that become aspartic acid and Q are Glutamines that become deamidated. M corresponds to Methionies that become oxidized. FIG.16 is a schematic explanation of the method used to calculate percentage ratios of modified amino acids at specific locations along the sequence of each peptide. FIG.17 illustrates an Anion exchange chromatography and size exclusion chromatography scheme of the isolation of Low Skid silk / modified peptide compositions. Low Skid silk / modified polypeptide compositions is composed of a variety of peptide populations, in a wide range of sizes and charge. Using Q- Sepharose anion exchange chromatography as a first step, and HiLoad Superdex 200 size exclusion chromatography as a second purification step, distinct populations of Low Skid silk / modified polypeptide compositions were separated. The Q-Sepharose eluate was loaded onto HiLoad Superdex 200 size exclusion chromatography, which resulted in negatively charged silk compositions / modified peptides fractionated by size. FIG.18A and FIG.18B are chromatograms of the anion exchange chromatography and the following size exclusion chromatography of the eluate (Q- eluate) of Low Skid silk / modified polypeptide compositions. FIG.18A: Anion exchange chromatography was performed with a Q-Sepharose column (Cytiva). Low Skid silk / modified peptide compositions were separated to uncharged peptide population (flowthrough – light blue background) and eluted negatively charged silk compositions (eluate – light pink background) by anion exchange chromatography. Light yellow background indicates column wash with 50 mM Tris pH=8.0 before eluting the charged peptide population. FIG.18B: The negatively charged eluate was loaded onto the Superdex 200 column and was flowed through the column with 50 mM Tris, 200 mM CaCl2, pH=8.0. When the UV-280 absorbance started to increase fractions were collected to separate the Low Skid silk / modified peptide compositions by size. The relative elution volume of silk compositions AS77 and AS81 are indicated on the chromatogram. FIG.19A and FIG.19B illustrates the Analytical Size Exclusion Chromatography of Low Skid silk / modified silk compositions and their constituent AS compositions. FIG.19A. Average molecular weight in kDa of Low Skid silk (LS) and AS77-AS81 are shown. FIG.19B. Polydispersity (PDI) measurements are shown. The numerical data is presented in Table F. FIG.20 is a SDS polyacrylamide gel electrophoresis of Low Skid silk / modified polypeptide compositions. Lanes are indicated by fraction number, at the order of elution from the Superdex 200 column, and their respective silk composition: fraction 6 is AS77, fraction 7 is AS78, fraction 8 is AS79, fraction 9 is AS80, and fraction 10 is AS81. FIG.21A and FIG.21B are graphs illustrating self-assembly reactions of the of the Low Skid silk / modified peptide compositions. Mid Skid Silk reaction was used as a positive control. FIG.21A. Illustrate kinetic parameters of gel formation during self-assembly of silk. Self-Assembly parameters of Mid Skid silk: Amax is 0.6780 (Abs), SARF is 8.676, T0.5 is 3.668 h, and the FSAF is 3.08 (Abs / min). FIG.21B. Is a snapshot of a later time point of the same self-assembly assay, 12 days after setting the assay. None of the tested fraction has self-assembled over time. FIG.22A and FIG.22B illustrate the characterization of Low Skid silk compositions by Dynamic Light Scattering. Low skid silk / modified peptide compositions were diluted to a concentration of 1 mg / mL, filtered, and analyzed by the Zetasizer Pro to estimate the diameter particle size of each silk composition. FIG. 22A. Illustrates intensity diameter particle size distribution measured for silk compositions AS77, AS78, AS79, AS80, and AS81. FIG.22B. Illustrate correlogram functions of silk compositions AS77, AS78, AS79, AS80, AS81. FIG.23 illustrates size exclusion chromatography scheme of the isolation of Low Skid silk / modified peptide compositions. Low Skid silk / modified polypeptide compositions is composed of a variety of peptide populations, in a wide range of sizes, using HiLoad Superdex 200 size exclusion chromatography, distinct populations of Low Skid silk / modified polypeptide compositions were separated. FIG.24 is a chromatogram of Low Skid silk / modified polypeptide compositions loaded onto a Superdex 200 gel filtration column. Low Skid silk / modified peptide compositions were loaded onto the Superdex 200 column and were flowed through the column with 50 mM Tris, 200 mM CaCl2, pH=8.0. When the UV-280 absorbance started to increase fractions were collected to separate the Low Skid silk / modified peptide compositions by size. The relative elution volume of silk compositions AS82, AS86, and AS87 are indicated on the chromatogram. FIG.25A and FIG.25B illustrate Analytical Size Exclusion Chromatography of Low Skid silk / modified silk compositions and their constituent AS compositions. Fig. QA. Illustrates average molecular weight in kDa of Low Skid silk (LS) and AS82-AS89 are shown. FIG.25B. Polydispersity (PDI) measurements are shown. The numerical data is presented in Table H. FIG.26 is an SDS polyacrylamide gel electrophoresis of Low Skid silk / modified polypeptide compositions. Lanes are indicated by fraction number, at the order of elution from the Superdex 200 column, and their respective silk composition: fraction 6 is AS82, fraction 7 is AS83, fraction 8 is AS84, fraction 9 is AS85, and fraction 10 is AS86. FIG.27A and FIG.27B are graphs illustrating self-assembly reactions of the of the Low Skid silk / modified peptide compositions. Mid Skid Silk reaction was used as a positive control. FIG.27A. Illustrates kinetic parameters of gel formation during self-assembly of silk. Self-Assembly parameters of Mid Skid silk: Amax is 0.6978 (Abs), SARF is 8.591, T0.5 is 3.361 h, and the FSAF is 3.46 (Abs / min). FIG.27B. Is a snapshot of a later time point of the same self-assembly assay, 18 days after setting the assay. AS87, AS88, and AS89 demonstrate gel formation at this time point, that was already observed five days post assay (LS, Low Skid silk; MS, Mid Skid silk). FIGS.28A-28C are graphs showing characterization of Low Skid silk compositions by Dynamic Light Scattering. Low skid silk / modified peptide compositions were diluted to a concentration of 1 mg / mL, filtered, and analyzed by the Zetasizer Pro to estimate particle size of each silk composition. FIG.28A. Shows intensity particle size distribution measured for silk compositions AS82, AS83, AS84, AS85, AS86, AS87, AS88, and AS89. FIG.28B. Shows intensity particle size distribution measured for silk compositions AS82, Low Skid silk / modified peptide compositions (LS), and Mid Skid silk / modified peptide compositions (MS). FIG. 28C. Shows correlogram functions of silk compositions AS82, AS83, AS84, AS85, AS86, AS87, AS88, AS89, Low Skid silk / modified peptide compositions (LS), Mid Skid silk / modified peptide compositions (MS). FIG.29 illustrates anion exchange chromatography (Q), hydrophobic interaction chromatography (HIC), and size exclusion chromatography (SEC) scheme of the isolation of Low Skid silk / modified peptide compositions. Low Skid silk / modified polypeptide compositions is composed of a variety of peptide populations, in a wide range of sizes and charge. Using Q-Sepharose anion exchange chromatography as a first step, Butyl ImpRes Hydrophobic interactions resin as a second step, and HiLoad Superdex 200 size exclusion chromatography as a third purification step, distinct populations of Low Skid silk / modified polypeptide compositions were isolated. The Q-Sepharose eluate was loaded onto a Butyl ImpRes (HIC) column, and the HIC-eluate was loaded onto a HiLoad Superdex 200 size exclusion chromatography, which resulted in fractionation of negatively charged silk compositions / modified peptides with hydrophobicity characteristics fractionated by size. The Q-Sepharose eluate contained negatively charged peptides in all sizes. Resolving these peptides by Butyl ImpRes column resulted in elution of high- molecular-weight, negatively charged, somewhat hydrophobic silk compositions / modified peptides. The smaller negatively charged peptides were washed as flowthrough and did not bind the Butyl ImpRes column. The Q- HIC(elution) was loaded into Superdex 200 and was separated by size. FIGS.30A-30E are chromatograms of anion exchange chromatography, hydrophobic interactions chromatography, and the following size exclusion chromatography of Low Skid silk / modified polypeptide compositions. FIG.30A. illustrates anion exchange chromatography was performed with a Q-Sepharose column. Low Skid silk / modified peptide compositions were separated to uncharged peptide population (flowthrough – light blue background) and eluted negatively charged silk compositions (eluate – light pink background) by anion exchange chromatography. Light yellow background indicates column wash with 50 mM Tris pH=8.0 before eluting the charged peptide population. FIG.30B. illustrates the negatively charged eluate (Q-elution) was loaded onto a Butyl ImpRes column, in the presence of 300 mM ammonium sulfate [(NH4)2SO4], to expose hydrophobic domains of the silk peptides, which allows binding to the column. The highly charged peptide population did not bind the column (flowthrough), highlighted in light blue. The column was washed until OD280 was reduced to ~100 units (light yellow). Then, the bound silk peptides (Q-HIC(elution)) were eluted by using 50 mM Tris, pH=8.0 without ammonium sulfate (light pink). FIG.30C. illustrates the Q-HIC(elution) was further fractionated by size exclusion chromatography (SEC), using the gel filtration column Superdex 200. The Q-HIC(elution) fraction was flowed through the column with 50 mM Tris, 200 mM CaCl2, pH=8.0. When the UV-280 absorbance started to increase fractions were collected to separate the Low Skid silk / modified peptide compositions by size. The relative elution volume of silk compositions AS90 and AS94 are indicated on the chromatogram. FIG.30D. the Q-HIC(flowthrough) fraction was further fractionated by SEC, using the Superdex 200 column, at the same procedure as in (VC). The relative elution volume of silk compositions AS95 and AS100 are indicated on the chromatogram. FIG.30E. illustrates the superimposition of chromatograms (FIG.30C) and (FIG.30D). the Q-HIC(elution) fraction has a higher-molecular-weight range compared to the Q-HIC(flowthrough) fractions, which elutes later in SEC, and has lower-molecular-weight range. FIG.31A and FIG.31B are graphs showing analytical Size Exclusion Chromatography of Low Skid silk / modified silk compositions and their constituent AS compositions. FIG.31A. Average molecular weight in kDa of Low Skid silk (LS) and AS90-AS100 are shown. FIG.31B. Polydispersity (PDI) measurements are shown. The numerical data is presented in Table 11. FIG.32A and FIG.32B are SDS polyacrylamide gel electrophoresis of Low Skid silk / modified polypeptide compositions. FIG.32A. Q-HIC(elution) SEC fractions. FIG.32B. Q-HIC(flowthrough) SEC fractions. Lanes are indicated by fraction number, at the order of elution from the Superdex 200 column, and their respective silk composition: in FIG.32A, fraction 6 is AS90, fraction 7 is AS91, fraction 8 is AS92, fraction 9 is AS93, and fraction 10 is AS94. In FIG.32B, fraction 8 is AS95, fraction 9 is AS96, fraction 10 is AS97, fraction 11 is AS98, fraction 12 is AS99, and fraction 13 is AS100. FIG.33 illustrates self-assembly reactions of the of the Low Skid silk / modified peptide compositions. Mid Skid Silk reaction was used as a positive control. kinetic parameters of gel formation during self-assembly of silk. Q- HIC(elution) is the elution fraction that was eluted from the Butyl ImpRes column, prior to SEC purification; LS, Low Skid silk; MS, Mid Skid silk. Self-Assembly parameters of Mid Skid silk: Amax is 0.6974 (Abs), SARF is 8.661, T0.5 is 3.834 h, and the FSAF is 3.03 (Abs / min). FIGS.34A-34F illustrate the characterization of Low Skid silk compositions by Dynamic Light Scattering. Low and Mid skid silk / modified peptide compositions were diluted to a concentration of 1 mg / mL, filtered, and analyzed by the Zetasizer Pro to estimate the diameter particle size of each silk composition. In FIG.34A, intensity diameter particle size distribution measured for silk compositions AS90, Q- HIC(elution) fraction (prior to fractionation by SEC), Low Skid silk (LS), and Mid Skid silk (MS). FIG.34B: Correlogram functions of silk compositions presented in (FIG.34A). FIG.34C: Intensity diameter particle size distribution measured for silk compositions AS90-AS94, derived from Q-HIC(elution)-SEC fractionation process. FIG.34D: Correlogram functions of silk compositions presented in (FIG.34C). FIG. 34E: Intensity diameter particle size distribution measured for silk compositions AS95-AS100, derived from Q-HIC(flowthrough)-SEC fractionation process. FIG. 34F: Correlogram functions of silk compositions presented in (FIG.34E). FIG.35 illustrates size exclusion chromatography scheme of the isolation of Mid Skid silk / modified peptide compositions. Mid Skid silk / modified polypeptide compositions is composed of a variety of peptide populations, in a wide range of sizes, using HiLoad Superdex 200 size exclusion chromatography, distinct populations of Mid Skid silk / modified polypeptide compositions were able to be separated. FIG.36 is a chromatogram of Mid Skid silk / modified polypeptide compositions loaded onto a Superdex 200 gel filtration column. Mid Skid silk / modified peptide compositions were loaded onto the Superdex 200 column and were flowed through the column with 50 mM Tris, 200 mM CaCl2, pH=8.0. When the UV-280 absorbance started to increase fractions were collected to separate the Mid Skid silk / modified peptide compositions by size. The relative elution volume of silk compositions AS107 and AS111 are indicated on the chromatogram. FIG.37 and FIG.37B illustrates analytical Size Exclusion Chromatography of Mid Skid silk / modified silk compositions and their constituent AS compositions. In FIG.37A average molecular weight in kDa of Mid Skid silk (MS) and AS106-AS111 are shown. In FIG.37B polydispersity (PDI) measurements are shown. The numerical data is presented in Table 13. FIG.38 is a SDS polyacrylamide gel electrophoresis of Mid Skid silk / modified polypeptide compositions. Lanes are indicated by fraction number, at the order of elution from the Superdex 200 column, and their respective silk composition: fraction 6 is AS107, fraction 7 is AS108, fraction 8 is AS109, fraction 9 is AS110, and fraction 10 is AS111. FIG.39 illustrates self-assembly reactions of the of the Mid Skid silk / modified peptide compositions. kinetic parameters of gel formation during self-assembly of silk. Dashed red lines show how the self-assembly parameters Amax, SARF, and T0.5 were calculated for unfractionated Mid Skid silk (MS). Numerical parameters of silk compositions AS106-AS111 can be found in Tables 12-14. Low Skid silk (LS) was used as a negative control. LS, Low Skid silk; MS, Mid Skid silk. FIG.40A and FIG.40B illustrates characterization of Mid Skid silk compositions by Dynamic Light Scattering. Mid skid silk / modified peptide compositions were diluted to a concentration of 1 mg / mL, filtered, and analyzed by the Zetasizer Pro to estimate particle size of each silk composition. FIG.40A shows intensity particle size distribution measured for silk compositions AS106, AS107, AS108, AS109, AS110, AS111, and Mid Skid (MS). FIG.40B showscorrelation functions of silk compositions presented in (FIG.40A). FIG.41 illustrates anion exchange chromatography and size exclusion chromatography scheme of the isolation of Mid Skid silk / modified peptide compositions. Mid Skid silk / modified polypeptide compositions is composed of a variety of peptide populations, in a wide range of sizes and charge. Using Q- Sepharose anion exchange chromatography as a first step, and HiLoad Superdex 200 size exclusion chromatography as a second purification step, distinct populations of Mid Skid silk / modified polypeptide compositions were separated. The Q-Sepharose eluate was loaded onto HiLoad Superdex 200 size exclusion chromatography, which resulted in negatively charged silk compositions / modified peptides fractionated by size. FIG.42A and FIG.42B are chromatograms of the anion exchange chromatography and the following size exclusion chromatography of the eluate (Q- eluate) of Mid Skid silk / modified polypeptide compositions. FIG.42A. Anion exchange chromatography was performed with a Q-Sepharose column (Cytiva). Mid Skid silk / modified peptide compositions were separated to uncharged peptide population (flowthrough – light blue background) and eluted negatively charged silk compositions (eluate – light pink background) by anion exchange chromatography. Light yellow background indicates column wash with 50 mM Tris pH=8.0 before eluting the charged peptide population. FIG.42B. The negatively charged eluate (Q- elution) was loaded onto the Superdex 200 column and was flowed through the column with 50 mM Tris, 200 mM CaCl2, pH=8.0. When the UV-280 absorbance started to increase fractions were collected to separate the Mid Skid silk / modified peptide compositions by size. The relative elution volume of silk compositions AS101 and AS105 are indicated on the chromatogram. FIG.43A and FIG.43B illustrate analytical Size Exclusion Chromatography of Mid Skid silk / modified silk compositions and their constituent AS compositions. In FIG.43A, average molecular weight in kDa of Mid Skid silk (MS) and AS101-AS105 are shown. In FIG.43B, polydispersity (PDI) measurements are shown. The numerical data is presented in Table 16. FIG.44A is a SDS polyacrylamide gel electrophoresis of Mid Skid silk / modified polypeptide compositions. Lanes are indicated by fraction number, at the order of elution from the Superdex 200 column, and their respective silk composition: fraction 6 is AS101, fraction 7 is AS102, fraction 8 is AS103, fraction 9 is AS104, and fraction 10 is AS105. FIG.44B illustrates self-assembly reactions of the of the Mid Skid silk / modified peptide compositions. Low Skid Silk reaction was used as a negative control. Kinetic parameters of gel formation during self-assembly of silk are shown. Red dotted lines are shown to clarify the calculations of Amax, SARF (Self-Assembly Rate Factor), and T0.5 parameters in Table 17. FIGS.45A-45C are graphs illustrating characterization of Mid Skid silk compositions by Dynamic Light Scattering. Mid skid silk / modified peptide compositions were diluted to a concentration of 1 mg / mL, filtered, and analyzed by the Zetasizer Pro (Malvern) to estimate the diameter particle size of each silk composition. FIG.45A: Intensity diameter particle size distribution by intensity measured for silk compositions AS101, AS102, AS103, AS104, and AS105. FIG. 45B: Intensity diameter particle size distribution by intensity measured for silk compositions AS101, AS105, and Mid Skid silk (MS), to emphasize the size difference between AS101 and AS105. FIG.45C: Correlogram functions of silk compositions AS101, AS102, AS103, AS104, AS105, and Mid Skid silk (MS). FIG.46 is an illustration of the values for three molar mass moments (Mn, Mw, and Mz) as it relates to molar mass and the number of molecules at each molar mass. This example is applicable to a polydisperse sample; for a monodisperse sample, Mn = Mw = Mz. FIG.47A and FIG.47B are analytical SEC-MALS of Low, Mid and High Molecular Weight Silk. FIG.47A. Weight Average Molecular Weight in kDa of Low, Mid, and High Molecular Weight Silk. FIG.47B: Polydispersity Index (PDI) measurements of Low, Mid, and High Molecular Weight Silk are shown. FIG.48A and FIG.48B are analytical SEC-MALS of Low, Mid and High Molecular Weight Silk organized by Silk Type. Individual data points are show and the mean is represented by the heigh of the box. The bars encompass one standard deviation. FIG.48A. Weight-Average Molecular Weight Ranges for Low, Mid, and High Molecular Weight Silk. FIG.48B. PDI Ranges for Low, Mid, and High Molecular Weight Silk. FIG.49A and FIG.49B are analytical SEC-MALS of Low Skid silk / modified silk compositions and the constituent AS compositions as separated by Q-SEC (Q- eluent). FIG 49A: Average molecular weight in kDa of Low Skid silk (LS) and AS77- AS81 are shown. FIG.49B: Polydispersity (PDI) measurements are shown. The numerical data is presented in Table 24. FIG.50A and FIG.50B are analytical SEC-MALS of Low Skid silk / modified silk compositions and the constituent AS compositions as separated by SEC. FIG. 50A: Average molecular weight in kDa of Low Skid silk (LS) and AS82-AS89 are shown. FIG.50B: Polydispersity (PDI) measurements are shown. The numerical data is presented in Table 25. FIG.51A and FIG.51B are analytical SEC-MALS of Low Skid silk / modified silk compositions and the constituent AS compositions as separated by Q-HIC-SEC (Q-HIC-Eluent). FIG.51A: Average molecular weight in kDa of Low Skid silk (LS) and AS90-AS94 are shown. FIG.51B. Polydispersity (PDI) measurements are shown. The numerical data is presented in Table 26. FIG.52A and FIG.52B are analytical SEC-MALS of Low Skid silk / modified silk compositions and the constituent AS compositions as separated by Q-HIC-SEC (Q-HIC-Flowthrough). FIG.52A: Average molecular weight in kDa of Low Skid silk (LS) and AS95-AS100 are shown. FIG.52B: Polydispersity (PDI) measurements are shown. The numerical data is presented in Table 26. FIG.53A and FIG.53B are analytical SEC-MALS of Mid Skid silk / modified silk compositions and the constituent AS compositions as separated by Q--SEC (Q- flow through). FIG.53A: Average molecular weight in kDa of Mid Skid silk (MS) and AS101-AS105 are shown. FIG.53B:Polydispersity (PDI) measurements are shown. The numerical data is presented in Table 27. FIG.54A and FIG.54B are analytical SEC-MALS of Mid Skid silk / modified silk compositions and the constituent AS compositions as separated by SEC. FIG. 54A: Average molecular weight in kDa of Mid Skid silk (MS) and AS106-AS111 are shown. FIG.54B: Polydispersity (PDI) measurements are shown. The numerical data is presented in Table 28. FIG.55A and FIG.55B are graphs showing secretion of pro- (FIG.55A) and anti-inflammatory (FIG.55B) cytokines from PMA differentiated macrophages. Supernatant from PMA induced macrophages treated with LPS from E.coli O111:B7 was analyzed with DuoSet ELISA assays and the amount of released cytokine was quantified. Results were analyzed with unpaired t-test (n=3). FIG.56A depicts Biotin-labeled LOW (left panel) or MID (middle panel) Skid silks were applied to keratinocyte cell culture for 1 hour, rinsed extensively with HBSS, fixed and visualized with Streptavidin 594 (red). Cell boundaries are labeled with WGA-488 (green). Cells pretreated with 2 mM CaCl2 overnight showed increase silk binding (right panel). FIG.56B depicts single silk assembly (red) composed of sheets and filaments (yellow and blue insets, respectively) contiguously spans 20 cells simultaneously (individually numbered in merge image; cell bodies determined with WGA-488 stain in green). This pattern is especially apparent in cells pretreated with physiological calcium. FIG.56C depicts orthogonal projections of silk+ cells pretreated with physiological CaCl2 overnight showing localization of biotin-silk polypeptides to supranuclear domains on the apical surface of adjacent cells. FIG.57A depicts aschematic of a single silk assembly spanning two adjacent cells. Silk assemblies localize at the cell surface (top panel, “axial view”) and tend to occupy a supranuclear apical domain. Apical view (bottom panel) shows silk assembly as viewed in image data. FIG.57B depicts a schematic of two models for silk assembly formation. Model 1 posits that silk polypeptide monomers bind to cell surface and polymerize, thus forming de novo. Model 2 posits that large, pre-formed silk aggregates bind to cells and each other, giving rise to the large micron scale structures observed in the data. FIG.57C shows Model 1 predicts that diluting labeled silk with increasing amounts of unlabeled should result in a gradual, diffuse, uniform dimming of silk fluorescence intensity. FIG.57D shows Model 2 predicts that diluting large, labeled silk aggregates with large, unlabeled silk aggregates should result in non-uniform, mosaic dilution of silk assembly fluorescence resulting in an increasing number of assembly “gaps” as the ratio of labeled to unlabeled silk drops. These “gaps” should be proportional to individual silk aggregate size. FIG.58A depicts a reiteration of Model 1, which predicts small monomer polymerization drive silk assembly on cell surface and the prediction of uniform diffuse dilution of silk assembly fluorescence by unlabeled silk. FIG.58B depicts a dt plot with mean + / - 95% confidence interval (blue line, red error bars, respectively) showing progressive dose-dependent dilution of silk assembly by unlabeled silk. FIG.58C shows representative images of “100% labeled” and “25% Labeled; 75% Unlabeled” silk assemblies on the surface of various cell bodies (white dashes). Note the diffuse, uniform dilution of fluorescence intensity (calibration color bar, right panel) associated with diluted silk assembly, thus supporting Model 1. FIG.58D depicts multi-pass line scan measurement done on data in (FIG. 58C) (red dashed and blue dashed lines were used to calculate 1D fluorescence intensity traces) showing dilution of fluorescence intensity that is evenly distributed within the assembly, again supporting Model 1. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001, Mann Whitney U nonparametric test. FIGS.59A-59C illustrate ΜID Skid silk is retained on skin surface after detergent rinse-off in organotypic 3D skin model. (FIG.59A) Schematic showing the anatomical views presented in the reconstructions. (FIG.59B) Negative control samples treated with unlabeled 33B for 1 hour lack signal. (FIG.59C) Experimental conditions showing various degrees of 33B deposits (blue) on the surface of the skin. Stratum granulosum (“sg”; orange) cells are labeled with 488-WGA. Note the gap between 33B sheets and the sg, presumably populated by stratum corneum (unlabeled). SLES + Stringent rinse-off samples show reduced 33B yet punctate silk deposits are retained (white arrowheads). FIGS.60A-60C depict apical projections of 33B localization on skin surface after rinse-off. (FIG.60A) Schematic showing the anatomical views presented apical projections. (FIG.60B) Negative control samples treated with unlabeled 33B for 1 hour lack detectable fluorescence. (FIG.60C) Experimental conditions showing various degrees of 33B deposits (orange) on the surface of the skin. SLES and stringent rinse-off led to reduced 33B yet punctate deposits (white arrowheads) and diffuse networks of deposits (dashed boxes; enlarged and contrast-adjusted) are retained. FIGS.61A–61C illustrates. CaCl2treatment of keratinocytes boosts CD44 expression and silk binding to cells. (FIG.61A) Co-staining of cells for CD44 and Streptavidin 594 in cells either pretreated or not with CaCl2. CD44 expression is dramatically upregulated in a subpopulation of cells after calcium pretreatment – this subpopulation of cells is also more prone to bind silk (single-cell level correlation between these two are addressed below). (FIG.61B) Dose response association with percent of cells that were silk+ with calcium pretreatment (blue) or without (red). Both MID and LOW skid silk increase binding after calcium pretreatment. (FIG.61C) Quantification of % CD44 high-expressing cells in Mock-treated or Calcium- pretreated keratinocytes showing ~4-fold upregulation of CD44-high expressing cells. FIGS.62A–62D illustrate CD44 is required for silk binding to the cell surface of keratinocytes. (FIG.62A) Experiment schematic showing hypothesis of silk binding to CD44 receptor, which can be blocked by function-blocking CD44 antibody. (FIG.62B) Characteristic images showing cells stained for Biotin-Silk as well as CD44 blocking antibody (using 488-anti-rat IgG). Note the disappearance of silk + cells in the sample treated with CD44 blocking antibody, and the extracellular CD44 localization pattern, which bears resemblance to silk localization when CD44 is not blocked. (FIG.62C) 594-Streptavidin cell intensity plotted against 488-anti-rat IgG cell intensity showing positive and negative populations for CD44 and cells that bound silk. (FIG.62D) Quantification of silk+ cells by dose in samples treated with CD44 blocking antibody or IgG isotype control. FIGS.63A – 63C illustrate silk binding to epidermal keratinocytes is heterogeneous in cell populations and correlates with CD44 availability at the single cell level. (FIG.63A) 594-Streptavidin cell intensity plotted against endogenous CD44 levels. Cells that were positive for Silk binding were gated and used to generate regression plots. The slope of the regression line is written in black for positive values and red for negative values. (FIG.63B) For cells pre-treated with CD44 blocking antibody, the cells that bound the most silk tended to be the ones blocked with the least amount of CD44 blocking antibody, a trend that was not detected when analyzing the samples treated with the isotype control. (FIG.63C) Bottom panel shows a dose-response curve for various doses of Biotin-Silk plotted against the average % Silk+cells, which indicates the binding begins to saturate at 3 mg / ml. To generate the plot in the top panel, among Silk+cells, the ratio of %CD44Hito %CD44Lowwas calculated and plotted against biotin-silk dosage. At lower, sub saturating doses of silk, the silk tends to bind CD44Hicells more efficiently than CD44 low cells, a trend that decays as the dose approaches saturation. FIG.64A and FIG.64B depicts model for silk binding and assembly formation on human keratinocytes. (FIG.64A): Top panel: Localization pattern of extracellular CD44 in calcium pretreated cells showing supranuclear puncta. Middle panel: localization pattern of cell surface-bound LOW skid silk in calcium pretreated cells showing localization to supranuclear puncta on the cell, resembling a CD44-like localization pattern. Bottom panel: Localization pattern of cell surface-bound MID skid silk in calcium pretreated keratinocytes, showing not only a supranuclear localization but also a matrix-like sheet assembly that spans adjacent cells. (FIG. 64B): Model for silk interaction with human keratinocytes. Calcium pretreatment boosts CD44 levels leading to CD44 receptors at supranuclear plasma membrane domains. Silk polypeptides bind to CD44 receptors and thus show the same localization pattern. CD44 bound silk polypeptides begin to polymerize with unbound available silk polypeptides to form higher order sheet-like silk assemblies. FIG.65A and FIG.65B show a method for threshold estimation used to measure “percent positive” in single cell data. (FIG.65A): Example data from positive and negative controls for which data points along the x-axis are being iteratively evaluated based on a range of possible threshold values. (FIG.65B): % Positive cells measurement is plotted against various threshold positions for positive and negative control data, giving an approximation of the cumulative probability density function. The curve corresponding to the negative control decays rapidly as the threshold value approaches the “true threshold” and dramatically changes in slope after the value is reached, making an “elbow” in the curve (gray arrowhead). The difference between the two values (Δ) is also plotted which tends to peak near the “true threshold” value (dashed line) FIG.66 illustrates experimental workflow of immunofluorescence-based detection of Claudin-1 expression levels in human neonatal epidermal keratinocyte cells and hTERT-immortalized keratinocytes treated with MID SKID silk and LOW SKID silk. FIG.67 depicts representative immunohistochemistry images showing increase in claudin-1 (red stain) in cells (nuclei stained in blue) treated with 6.0mg / mL MID SKID and LOW SKID silk (0.6% w / v) compared to cells treated with only supplement-free media. FIGS.68A-68F depict MID SKID and LOW SKID silk increase Claudin-1 protein expression in primary human neonatal epidermal keratinocytes in vitro. Mean Claudin-1 intensity of each sample (0.5 - 6.0 mg / mL) was normalized to no treatment samples within each experiment and represented as a bar graph (FIG.684A: MID silk; FIG.68B: LOW silk) with error bars representing standard deviation of normalized data. Distribution of mean claudin-1 intensity for all treatments for at least 3 biological repeats (FIG 68C: MID silk; FIG.68D: LOW silk); Claudin-1 positive cell (%) in the cell population represented as bar graph shows dose-response based increase in claudin-1 expressing cell population with error bars representing standard deviation in biological repeats (FIG.68E: MID silk; FIG.68F: LOW silk). FIGS.69A-69F depict MID SKID and LOW SKID silk increase Claudin-1 protein expression in h-TERT immortalized keratinocytes in vitro. Mean Claudin-1 intensity of each sample was normalized to no treatment samples within each experiment and represented as a bar graph (FIG.69A: MID silk; FIG.69B: LOW silk) with error bars representing standard deviation of normalized data. Distribution of mean Claudin-1 intensity for all treatments for at least 3 technical repeats (FIG.69C: MID silk; FIG.69D: LOW silk); Claudin-1 positive cell (%) in the cell population represented as bar graph shows dose-response based increase in Claudin-1 expressing cell population with error bars representing standard deviation in biological repeats (FIG.69E: MID silk; FIG.69F: LOW silk). FIGS.70A–70D depict MID SKID silk and Ca2+ synergize to co-upregulate Claudin-1 and Involucrin1 in keratinocytes. (FIG.70A): Involucrin intensity plotted against Claudin-1 intensity for single cells from a single replicate in a co- immunofluorescence experiment. Samples were treated with CaCl2, 6 mg / ml MID SKID silk, or a combination of both. Dashed lines mark the position of algorithm- generated x, and y axis thresholds used for cell scoring. (FIG.70B): Percent Claudin- 1 positive cells are dramatically elevated upon combination treatment compared with CaCl2 or 6 mg / ml MID SKID alone. (FIG.70C): Percent Involucrin positive cells are dramatically elevated upon combination treatment compared with CaCl2or 6 mg / ml MID SKID alone. (FIG.70D): Cells doubly positive for Claudin-1 and Involucrin are dramatically elevated upon combination treatment compared with CaCl2or 6 mg / ml MID SKID alone. *p<0.05, **p<0.01, ***p<0.01, ****p<0.001, Student’s t-test, unpaired, two-tailed. FIG.71A and FIG.71B depict MID Skid Silk and Hyaluronic Acid similarly upregulate Claudin-1 in a dose-dependent manner. (FIG.71A): Representative Images of Ker-CT cells treated for 24 hours with either 6 mg / ml MID skid silk, 0.5 mg / ml HA or Mock treated. Cell membranes were labeled with 488-WGA and cells were immunostained for Claudin-1 (yellow, magenta in “Merge + DNA”, respectively). Claudin-1 upregulation by MID Skid silk or HA is accompanied by membrane localization and enrichment at cell-cell contacts (arrowheads), consistent with tight junction formation upon increased expression. (FIG.71B): Quantification of % Claudin-1 positive cells after exposure to various doses of MID Skid silk (top panel) or HA (bottom panel). *p<0.05, **p<0.01, ***p<0.01, ****p<0.001, Student’s t-test, unpaired, two-tailed. FIG.72A and FIG.72B depict cartoon schematics of collagen-1 production. (5-1A) Pro-collagen1A1 secreted by human dermal fibroblasts to the extracellular matrix is processed by collagenases to remove N- and C- terminal ends and produce mature collagen triple helix fibers. (FIG.72B): Collagen deposition (includes collagen-1) provides support and elasticity to the extracellular matrix. FIGS.73A–73C depict schematic of experiment setup and collagen production. (FIG.73A): Human dermal fibroblast cells in 2D culture are treated with Low Skid (27P) or Mid Skid (33B) silk peptides for 24 hrs at 37°C and 5% CO2. Secreted pro-collagen1A1 from supernatant samples is measured by ELISA and fixed cells are assessed for total deposited collagen by sirius red spectrophotometric assay. (FIG.73B, FIG.73C): ELISA results show significant increase in secreted levels of pro-collagen1A1 levels with treatment of 0.5 mg / mL Low Skid and 0.5 mg / mL Mid Skid silk peptides for 24 hrs. Data are averages of 2 technical replicates from 1 donor and error bars represent standard deviation. Test of statistical significance was performed using Brown-Forsythe and Welch ANOVA tests (multiple comparisons) between treated and no treatment samples and considered significant if p < 0.05. FIGS.74A–74C depict Silk increases levels of total collagen deposition by human dermal fibroblasts cells in 2D culture. (FIG.74A): Representative fluorescence microscopy images show increased total collagen deposition in sirius-red dye stained fibroblast cells treated with 2.0 mg / mL Low Skid and 2.0 mg / mL Mid Skid silk compared to untreated cells, and similar to TGF-B treated cells. (FIG.74B, FIG.74C) Quantification of collagen bound sirius red dye (absorbance at 540 nm) shows significant increase in total collagen deposition at 0.5 mg / mL Low Skid silk and 1.0 mg / mL Mid Skid silk peptides. Data are averages of 2 technical replicates from 1 donor and error bars represent standard deviation. Test of statistical significance was performed using the ordinary one-way ANOVA (multiple comparisons test) between treated and no treatment samples and was considered significant if p < 0.05. FIGS.75A–75C depict Silk does not alter cell-associated Col1A1 levels in human dermal fibroblasts 2D culture, indicating increase in Pro-Col1A1 secretion. (FIG.75A): Representative fluorescence microscopy images show no significant changes in cell-associated Col1A1 levels in fibroblast cells treated with 6.0 mg / mL Low Skid and 6.0 mg / mL Mid Skid silk compared to untreated cells, and similar to TGF-B treated cells. (FIG.75B, FIG.75C): Quantification of % Col1A1+ cell populations for Low skid and Mid skid dosages. Data are averages of one triplicate experiment from 1 donor and error bars represent standard deviation. Test of statistical significance was performed using an unpaired t-test between treated and no treatment samples and was considered significant if p < 0.05. FIG.76A and FIG.76B is a schematic overview of method development for silk receptor discovery. FIG.76A: Human cells (for example, keratinocytes or fibroblasts) are lysed to create whole cell lysate that contains the full proteome of the cells. The whole cell lysate is uploaded onto SDS-PAGE to separate the proteins into distinct bands based on their molecular weight. Then, part of the gel is stained with Coomassie stain to visualize the protein bands, and some is blotted on PVDF membrane for a Far Western Blot analysis. During the Far Western Blot analysis, the membrane is incubated with biotinylated silk to allow interactions with potential receptors. FIG.76B: The Far Western Blot membrane that was labeled with biotinylated silk, and the Coomassie-stained gel, are compared carefully, and bands in the Coomassie gel that share the exact molecular weight as the silk-binding bands in the blot are excised from the gel, and analyzed by LC / MS. Once the proteins of interest are identified by LC / MS, the Far Western Blot (with biotinylated silk) is performed side-by-side with a standard western blot, using specific antibodies against the identified proteins to validate they share the same molecular weight. Lane 1 – cell lysate labeled with biotinylated silk; lane 2 - cell lysate labeled with a specific antibody that corresponds to the protein identified by LC / MS in the upper band of the Far Western Blot; lane 3 - cell lysate labeled with a specific antibody that corresponds to the protein identified by LC / MS in the lower band of the Far Western Blot. In lane 1, bands that did not bind silk are colored in black to clarify the specificity of the assay, and are not visible in the actual Far Western Blot. FIG.77 is a SDS polyacrylamide gel electrophoresis of cell lysates. Cells of Ker-CT cell line and primary fibroblasts were lysed, and total protein content was determined. Each lane contains 20 µg of total protein for each lysate. Cell lysates were loaded side by side to compare the proteomes of the two cell types. The gel was stained with Coomassie stain. Ker – Ker-CT cell line. FIG.78 shows specific silk binding to potential targets analyzed by Far Western Blot. Keratinocyte (KerCT cell line) lysate was loaded onto SDS-PAGE, separated, and transferred onto a PVDF membrane for further labeling. Membranes were incubated with either a specific antibody against CD44 (anti-CD44), 1500 kDa biotinylated Hyaluronic acid (HA), biotinylated Low Skid (LS-biotin), or biotinylated Mid Skid (MS-biotin). The following step was incubation with either a secondary antibody (for anti-CD44 labeling) conjugated to HRP (horseradish peroxidase), or streptavidin conjugated to HRP (for HA and biotinylated silk). Addition of HRP substrate and exposure of the membrane revealed silk binding to specific bands, and Hyaluronic acid binding to CD44 (positive control to show that proteins are capable of refolding after SDS removal and can bind their specific ligands). FIG.79A and FIG.79B illustrate identification of potential silk-binding proteins in cell lysates by combining SDS-PAGE and Far Western Blot. FIG.79A: Identification of potential silk-binding proteins in keratinocytes. Cell lysates of keratinocytes cell line Ker-CT were run on an SDS-PAGE and were stained with Coomassie or blotted on a PVDF membrane for labeling with silk (Far Western Blot). The SDS-PAGE and the blot were compared, and bands on the SDS-PAGE that matched silk-binding bands on the blot were excised and analyzed by LC / MS. The excised bands are labeled by numbers 1-6 and highlighted by asterisks (*) on the blot and the SDS-PAGE. FIG.79B: Identification of potential silk-binding proteins in fibroblasts. Cell lysates of primary fibroblasts and Ker-CT cell line (as a reference) were run on an SDS-PAGE and were stained with Coomassie or blotted on a PVDF membrane for labeling with silk (Far Western Blot). The SDS-PAGE and the blot were compared, and bands on the SDS-PAGE that matched silk-binding bands on the blot were excised and analyzed by LC / MS. The excised bands are labeled by numbers 7-9 and highlighted by asterisks (*) on the blot and the SDS-PAGE. LS-biotin – biotinylated Low Skid silk; Ker – Ker-CT cell line (keratinocytes). FIG.80 shows labeling of silk-binding target proteins by specific antibodies. Following identification of potential silk-binding proteins by LC / MS, the potential target proteins were labeled with specific antibodies to validate their molecular weight and relative position on a blot compared to Far Western Blot with biotinylated Low Skid silk. Cell lysates of keratinocytes (Ker-CT cell line) were loaded onto SDS- PAGE and were either stained with Coomassie stain or transferred to a PVDF membrane for Western blot or Far Western Blot analysis. The membranes were labeled with biotinylated Low Skid silk (LS), anti-keratin Type II cytoskeletal 5 (Ker5), anti-protein disulfide isomerase (PDI), or anti-annexin A2. Bands that correspond to Ker5, PDI, and Annexin A2 are highlighted by an asterisk (*). Estimated molecular weights of the target proteins: Ker5 – 62.37 kDa; PDI – 57.11 kDa; Annexin A2 – 38.6 kDa. FIG.81 illustrates 33Bα-113 binding to keratinocytes and matrix-like assembly occurs on the cell surface and is fluorescent tag-independent. Fluorescent image of 33B-⍺113Biotin (green) bound to human keratinocytes in culture after staining with streptavidin-594 and counterstaining DNA with Hoesch 33342 under non-permeabilizing conditions. Punctate, filamentous, and matrix-like localization patterns are highlighted by white boxes and magnified insets. FIGS.82A-82C illustrate results of the single-arm clinical study with a simple serum formulation containing 4% 33B-⍺113 peptides. (FIG.82A): Schematic structure of the epidermis. The four layers containing keratinocytes are shown with different colors and cell sizes. The uppermost layer, Stratum Corneum contains mostly keratin and dead keratinocyte cell debris. Magnified inset (lower left panel) showing network of proteins that connect adjacent keratinocyte cells and contribute to the epidermis physical barrier. (FIG.82B): Summary of the efficacy of the serum on improving hydration (measured by Corneometer), radiance, firmness and smoothness of skin (measured by expert visual grading) over a 28-day use period. All parameters showed a statistically significant improvement over baseline measurements. (FIG. 82C): Decreases in parameters associated with skin aging, following 28-day use of 33B-⍺113 serum. Statistically significant decreases were measured in desquamation (quantified by D-Squame analysis), erythema and rhytids (measured by expert visual grading), and mean TEWL (as measured by Tewameter) were recorded. Statistical significance: ✻ = p<0.05, ✻✻ = p<0.01, ✻✻✻ = p<0.001, ✻✻✻✻ = p<0.0001, N.S.= Not FIGS.83A-83C show 33B-⍺113 silk peptides restore claudin-1 expression in human skin and regulate the expression of skin barrier proteins. (FIG.83A): Expression of proteins in skin explants after 33B-⍺113 silk peptide (4%) application. Black circles correspond to proteins that showed non-significant differences between 33B-⍺113 silk peptide-treated and water-treated explants. Red circles and cyan circles correspond to proteins that were significantly upregulated or downregulated, respectively, after treatment with 33B-⍺113 silk peptides.33B-⍺113 silk peptides were applied 3 times over 40h and then proteins were extracted from skin explants, quantified and identified with LC / MS. (FIG.83B): Quantification of claudin-1 expression after acetone stripping skin biopsy samples and recovery in the presence of water, or ceramides (0.05%) and 33B-⍺113 silk peptide application (2% and 4%). (FIG.83C): Representative human skin explant sections after acetone stripping and subsequent treatment stained for Claudin-1 (red) and counterstained for nuclei (blue). Mean from 3 biological repeats for each treatment are shown with standard error of mean (SEM) as error bars. Statistical significance test was performed by ordinary one-way ANOVA against only acetone treated sample: ✻ = p<0.05, ✻✻ = p<0.01, ✻✻✻ = p<0.001, ✻✻✻✻ = p<0.0001, N.S.= Not Significant. FIGS.84A-84C show results of the placebo-controlled clinical study with a simple serum formulation containing 2% 33B-⍺113 peptides. FIG.84A. Average reduction in erythema, FIG.84B: rhytids (as assessed by an expert grader) and FIG. 84C:, TEWL (measured via Tewameter) after 7 and 28 days of serum use. The test group using the 33B-⍺113 peptide-containing serum (represented in black) experienced a significantly greater reduction in all parameters than did users using the placebo serum without any 33B-⍺113 (represented in white). Statistical significance: ✻ = p<0.05, ✻✻ = p<0.01, ✻✻✻ = p<0.001, ✻✻✻✻ = p<0.0001, N.S.= Not FIGS.85A-85E depict 33B-⍺113 binds to the surface of skin tissue in an organotypic epidermal tissue model and specifically binds to human keratinocytes in cell culture. (FIG.85A) Telomerase (h-TERT) immortalized and (FIG.85B) primary epidermal keratinocytes switch on claudin-1 expression after a single 24 h treatment with 33B-⍺113 silk peptides). (FIG.85C): Fluorescent image of 33B-⍺113A594 bound to human keratinocytes in culture. Four observed localization patterns are highlighted (dashed boxes; magnified insets): 33B-⍺113 negative cells (“1”), apical puncta (“2”), apical puncta with filament formation (“3”), and matrix assemblies that span neighboring cells (“4”). Similar patterns were obtained when 33B-⍺113 was visualized using a different tag (Supplementary Figure 1). (FFIG.85D): Percent of 33B-⍺113+ cells plotted against 33B-⍺113 dose showing dose-dependent binding to human keratinocytes. (FIG.85E) Confocal 3D reconstructions of organotypic human epidermis showing 33B-⍺113-JF525 retention (green) on the surface of skin when applied at 20%(w / v) in the presence of 20% (w / v) caprylyl / capryl glucoside followed by rinsing with water. Cell membranes are labeled with 488-WGA (magenta), allowing visualization of the stratum granulosum (“SG”). Mean from triplicate data are shown with standard error of mean (SEM) as error bars. Statistical significance: ✻ = p<0.05, ✻✻ = p<0.01, ✻✻✻ = p<0.001, ✻✻✻✻ = p<0.0001, N.S.= Not Significant. FIG.86 shows daily use of 33B-⍺113 (0.5%) body wash resulted in significant improvement in select skin barrier markers in subjects with eczema. A, An average 26.94% reduction in overall appearance of eczema (per the IGA scale, assessed by an expert grader) was experienced by subjects following 7 days of use. Erythema was similarly reduced, showing an average improvement of 40.42%. The average number of eczema lesions was reduced significantly following 7 days of usage, showing a 25.68% average reduction. transepidermal water loss (measured by Tewameter) was reduced to a statistically significant extent (5.88%) after a single use of 33B-⍺113- containing body wash, with additional reduction (11.82%) measured after 7 days of use. B. Skin hydration (measured by Corneometer) showed an immediate improvement of 6.97%, and 23.60% average improvement following 7 days of use. Statistical significance: ✻ = p<0.05, ✻✻ = p<0.01, ✻✻✻ = p<0.001, ✻✻✻✻ = p<0.0001, N.S.= Not Significant. FIGS.87A-87E illustrate 33B-113α matrices form by de novo assembly on the surface of human keratinocytes. (FIG.87A): Model for 33B matrix formation. 33B-113α peptides bind to the surface of keratinocytes forming apical puncta that can go on to nucleate filament outgrowths, which are in turn able to combine into networks of matrix-like assemblies spanning neighboring cells. (FIG.87B): De novo assembly predicts dilution of labeled with unlabeled 33B-⍺113 should result in uniform dilution of fluorescence intensity. (FIG.87C): **** p<0.0001 Mann Whitney U nonparametric test. Mean fluorescence intensity measurements for individual 33B matrix-like assembly at various dilutions of labeled:unlabeled 33B-⍺113 showing progressive dilution of fluorescence intensity. Error bars correspond to 95% confidence interval. (FIG.87D): Representative images of matrix-like assembly on cells (outlined in white dashed lines) either undiluted (Top panel) or diluted 4-fold with unlabeled 33B-⍺113 (bottom panel). False color scale relates to fluorescence intensity which decreases roughly 4-fold upon 4-fold dilution. (FIG.87E): Quantification of line scan depicted in (FIG.87D): shows dilution of fluorescent intensity is uniform throughout the assembly. FIGS.88A-88D illustrates 33Bα-113 binding to epidermal tissues occurs in diverse surfactant systems. Confocal 3D reconstructions of organotypic human epidermis showing 33B-⍺113-JF525 retention (green) on the surface of skin (“SG” labeled with WGA-488; magenta) when applied at 2%(w / v) in the presence of 2 % (w / v) caprylyl capryl glucoside (FIG.88B), Evolved By Nature body wash formulation (FIG.88C), or 1% SDS (w / v) (FIG.88D) followed by rinsing with water as compared to a control (FIG.88A). FIG.89 illustrates the Activated Silk 27P-Sterile “Alpha” two syringe system including two syringes and one Luer lock connector. The syringe on the left is 1 mL of sterile gel composed of hyaluronic acid (HA) crosslinked 27P. The syringe on the right is 0.3 mL of sterile 27P silk solution. FIGS.90A-90C are SEC-RI chromatograms of silk solution Lot: 006926023 (FIG.201A), silk solution Lot: 006926129 (FIG.201B), and silk solution Lot:10123284 (FIG.201C). FIG.91 shows SEC-RI chromatograms of three different lots of silk solution. FIG.92A depicts a 3D Skin equivalent model (MatTek) showing KDF polypeptides bind to the stratum corneum and penetrate through corneal layers to enter the epidermis. Topically applied silk peptides penetrate into skin and bind to stratum basale keratinocytes. FIG.92B depicts a 3D HSE MatTek model showing KDF polypeptides colocalize with corneal K1 filaments and directly bind K1 and K10. Far Western shows direct interaction of KDF peptides with HIS-Tagged K1 and K10 but not with BSA (control). KDF peptides are retained on the stratum corneum through direct protein interaction. FIG.92C depicts a schematic of stratified epithelium of epidermis illustrating keratin switching by basal cells entering differentiation. KDF polypeptides bind to corneal keratins. K5 and K14 are expressed by basal keratinocytes, K1 and K10 are expressed by differentiating keratinocytes. FIG.92D depicts a 3D HSE MatTek model showing KDF increases K1 expression in skin tissue. K1 is upregulated in KDF-treated epidermal tissue. Since KDF is enriched at the stratum corneum and differentiation-associated keratins are the most abundant proteins in the sc, we tested whether KDF polypeptides bind K1 and K10. FIG.92E shows KDF polypeptides upregulates Keratin 1 and Keratin 10 mRNA in primary keratinocytes (2D culture). KDF significantly increases Keratin 1 and Keratin 10 mRNA in primary keratinocytes. FIG.92F shows KDF polypeptides downregulate Keratin 5 mRNA in primary keratinocytes (2D culture). KDF-treated primary keratinocytes significantly reduce keratin 5 mRNA, suggesting switch in profile of keratin expression. FIG.93A depicts a 3D MatTek model showing KDF polypeptides that penetrate into the skin selectively bind to basal cells. FIG.93B shows KDF polypeptides form small / mobile and large / static puncta indicating receptor binding in diffusing puncta and static puncta. Ligand-receptor complexes are known to freely diffuse within the plasma membrane. Large, static puncta formation is consistent with KDF association with clustered receptors that also diffuse slowly. Small, rapidly-diffusing puncta is consistent with less clustered receptors which also have more mobility. FIG.93C shows KDF puncta associate with the keratinocyte cell surface. Stable association of KDF puncta with microvilli (labeled with WGA) indicates receptor-mediated binding to the cell surface. FIG.93D depicts a 3D HSE MatTek model showing KDF peptides selectively bind CD44hikeratinocytes in the epidermis. The correlation plot shows that CD44 is expressed in higher levels in basal vs suprabasal keratinocytes. FIG.93E shows blocking CD44 ligand binding site reduces KDF binding to keratinocytes. FIG.94 shows KDF polypeptides bind to the surface of 2D cultured human keratinocytes. Cells were treated with 6 mg / ml KDFBiotinand stained with Streptavidin-594 under nonpermeablized conditions. KDF polypeptides bind to human keratinocytes, forming puncta on the surface of the cells. Primary keratinocytes adopt a basal-like phenotype in culture, which is consistent with binding of KDF to stratum basale cells in tissue. FIG.95 shows KDF peptides interact with recombinant CD44 as assessed by ELISA assay. FIG.96A depicts schematic of stratified epithelium of epidermis showing increased tight junction protein expression during differentiation. FIG.96B depicts a 3D HSE MatTek Model showing KDF polypeptides globally boost CLDN1 production throughout epidermal tissue. CLDN1 boosted by KDF localizes to cell membranes, consistent with increased tight junctions. FIG.96C depicts images of 2D keratinocytes showing KDF polypeptides boost CLDN1 under basal and differentiating conditions. FIG.96D shows KDF polypeptides significantly upregulate CLND1 positively in primary keratinocytes under both basal and differentiating conditions, indicating CLDN1 boosting can affect cells of multiple strata. FIG.96E depicts a 3D HSE MatTek Model showing KDF polypeptides globally boost OCLN in epidermal tissue. KDF globally upregulates OCLN in various epidermal strata. Co-regulation of tight junction proteins and keratins by KDF strongly suggests it serves as a bona fide keratinocyte differentiating factor. FIG.96F depicts images of 2D keratinocytes showing KDF polypeptides boost OCLN under basal and differentiating conditions. FIG.96G shows KDF polypeptides significantly upregulate OCLN production in primary keratinocytes under both basal and differentiating conditions, indicating global induction of tight junctions in epidermal tissue. FIG.97 shows KDF polypeptides promote mRNA expression of tight junction proteins with Claudin-1 mRNA and Occludin mRNA. FIG.98A depicts a schematic of stratified epithelium of epidermis showing differentiation marker induction during epidermal stratification. Key protein markers associated with keratinocyte differentiation are Involucrin and Filaggrin. FIG.98B depicts a 3D HSE MatTek Model showing KDF polypeptides globally boost Involucrin (INV) production in epidermal tissue. Strong membrane localization is seen in suprabasal cells, indicating its maturation for corneal envelope production. The insert shows intense bands of cross-linked Involucrin enriched at the membrane of granulosum / corneocytes (are likely fated to be deposited on corneum). FIG.98C depicts images of 2D keratinocytes showing KDF polypeptides induce expression of Involucrin in keratinocytes under basal and differentiating conditions. FIG.98D shows KDF polypeptides significantly upregulate Involucrin in primary keratinocytes under both basal and differentiating conditions, indicating expression of Involucrin is a strong indicator that keratinocytes are undergoing differentiation. KDF induces an approximate 2-fold increase in percent Involucrin positively. FIG.98G depicts a 3D HSE MatTek Model showing KDF polypeptides globally boost Filaggrin (FILA) in epidermal tissue. KDF globally upregulates FilA in various epidermal strata. The effect is mostly seen in suprabasal cells, which enrich upregulated FilA in deposits. FIG.98H depicts images of 2D keratinocytes showing KDF polypeptides accelerate keratinocyte differentiation by boosting differentiation markers and promoting FilA maturation under basal and differentiating conditions. During differentiation Filaggrin gets processed for maturation in the cytosol. Nuclear localization of Filaggrin is predominantly observed under basal conditions. KDF treatment induces translocation of FilA from nucleus to cytosol within 24 hours. Cytosolic FilA begins to form puncta in keratohyalin granules for processing. This effect is seen under basal and differentiating conditions. FIG.98I shows KDF polypeptides increase cytonuclear FilA indicating KDF enhances natural differentiation. FIG.99 depicts stained FilA in whole-mount epidermal tissue of Stratum basale and Spinosum showing FilA subcellular localization phenotype, indicating nuclear to cytosolic translocation is associated with Basale to Spinosum transition. Thus, nuclear to cytosolic translocation of FilA is associated with progressive differentiation by suprabasal cells. FIG.100 shows KDF polypeptides promote mRNA expression of differentiation markers after 6 hours for Involucrin mRNA and Filaggrin mRNA. FIG.101 depicts a schematic of stratified epithelium of epidermis showing the mechanism of action for KDF polypeptide biological function and the differentiation factors that are boosted, suppressed, or bound to. FIG.102A and FIG.102B depict CD44 is expressed in the HCT116 and SW480, colon cancer cell lines with epithelial origin used to model intestinal epithelium. FIG.102A: HCT116 cells or FIG.102B SW480 cells immunostained for extracellular CD44 and visualized via confocal microscopy showing robust expression in both cell lines and distinct membrane localization. FIGS.103A-103J show 33BA594polypeptides bind to both HCT116 and SW480 cells in a dose-dependent manner and localize to perinuclear puncta on HCT116 cells. FIG.103A: HCT116 cells treated with Mock or FIG.103B: 6 mg / ml 33BA594for 1 hour followed by 4 washes showing localization to dominant single perinuclear puncta (FIG.103C). FIG.103D: SW480 cells treated with Mock or FIG. 103E: 6 mg / ml 33BA594with the same treatment regimen as above showing peptide binding but lack of puncta (FIG.103F. FIG.103G: Quantification of percent 33B- positive cells in the HCT116 cell line showing dose-dependent binding. FIG.103H: Quantification of percent 33B-positive cells in the SW480 cell line showing dose- dependent binding. FIG.103I: Quantification of percent of cells containing 33B puncta in HCT116 cell line. FIG.103J: Quantification of percent of cells containing 33B puncta in SW480 cell line showing SW480 cells with much less capacity to form 33B puncta. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001; Student’s t-test. FIGS.104A-104F show 33B boosts claudin-1 expression in both HCT116 and SW480 cells. FIG.104A: HCT116 cells treated with mock conditions. FIG.104B: HCT116 cells treated with 6 mg / ml 33B for 24 hours followed by fixation and staining for claudin-1. FIG.104C: SW480 cells were treated and stained in the same manner to FIG.104A. FIG.104D: SW480 cells were treated and stained in the same manner to FIG.104B. FIG.104E: Quantification of FIG.104A and FIG.104B showing dose-responsive increase in claudin-1 positivity at the single cell level. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001; Student’s t-test. FIG.104F: Quantification of FIG.104C and FIG.104D showing dose-responsive increase in claudin-1 positivity at the single cell level. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001; Student’s t-test.FIG.105A-105E depict 27P silk peptides penetrate through intact skin and bind to papillary fibroblasts in 3D skin equivalent model. FIG. 105A: Schematic of skin layer morphology of young and old skin depicting expression of specific markers associated with papillary and reticular fibroblasts. FIG. 105B: Schematic of experiment design to assess 27P silk penetration in 3D reconstituted Mattek skin model. FIG.105C: Line-scan analysis of intensity of 27P silk peptides along depth of dermis. FIG.105D: Representative images of mock and 27P silk treated 10 µm section of 3D skin samples showing penetration of silk through intact epidermis to papillary and reticular dermis. FIG.105E: Representative images of CD44 and silk-AF594 overlay in Mattek section showing more 27P silk puncta (white arrows) at papillary dermis than reticular dermis, similar to CD44 distribution. FIGS.106A-106F depict 27P silk binds to 2D dermal fibroblast cells and modulates CD44 localization. FIG.106A: Representative images of AF594-labeled 27P silk peptides binding to dermal fibroblast cells defined by WGA cell mask (magenta). FIG.106B: Labeled 27P silk dose-dependently binds to dermal fibroblast cells and reaches binding saturation > 1.0 mg / mL. FIG.106C: Representative images (CD44: magenta; DNA: blue), and FIG.106D: quantification of %CD44Highcells showing dose-dependent increase in CD44 extracellular translocation with 1hr treatment of low doses of 27P silk (0.0625 - 0.5 mg / mL). FIG.106E: Representative immunofluorescence images. FIG.106F: quantification (%CD44High) of fibroblast cells with CD44 (yellow) and DNA (cyan) showing no significant change in CD44 expression over 24h silk treatment. FIGS.107A-107E depict 27P silk dose-dependently induces pro-Col1A1 secretion and total collagen deposition in 2D fibroblasts. FIG.107A: Dose-dependent (0.25 - 2.0 mg / mL) induction of secreted pro-Col1A1 levels in dermal fibroblasts as assessed by ELISA shows 3-4 fold increase over 24h 27P silk treatment. FIG.107B: Combination of 27P silk treatment (0.25 - 2.0 mg / mL) and Vitamin C (50 µg / mL) shows synergistic increase in pro-Col1A1 secretion over 24h and subsequent 48h treatments. FIG.107C: Representative images of sirius red stained total collagen (red) deposited by dermal fibroblasts over 3 days (72h) of 27P silk and vitamin C (50 µg / mL) treatment. FIG.107D: 27P silk and vitamin C combination-induced prolonged increase in % total collagen deposition over 3 days (72h) and 5 (120h) days, measured by sirius red spectrophotometric assay. FIG.107E: Representative immunofluorescence images and quantification of populations of cells with high cell- associated extracellularly deposited Col1A1 (yellow) and intracellular Col1A1 (magenta) after 3 day (72h) 27P silk treatment. FIGS.108A-108D depicts translationally regulated de novo synthesis of intracellular collagens by silk in 2D fibroblasts. FIG.108A: Representative immunofluorescence images of intracellular Col1A1 protein (red) and Col3A protein (green) accumulated over 5 h of 24 h treatment with 27P silk and benchmarking ingredients; TGF-B treatment was considered as positive control. FIG.108B: Quantification of %Col1A1Highand %Col3AHighcells shows significant increases in de novo Col1A1 and Col3A with 24h treatment of low doses (0.25 - 0.5 mg / mL) of 27P silk. Intracellular Col1A1 and Col3A levels were significantly depleted with 50 µg / mL vitamin C treatment. FIG.108C: Accumulated intracellular Col1A1. FIG. 108D: intracellular Col3A with 27P silk (0.25 - 2.0 mg / mL) and vitamin C (50 µg / mL) combination over 24h shows 27P silk dose-dependent rescue of depletion resulted by vitamin C alone. FIGS.109A-109C show Fibrosis-associated markers are not induced by 27P silk treatment in 2D fibroblasts. FIG.109A: Representative immunofluorescence images of fibrosis marker, ɑ-SMA protein (magenta) in dermal fibroblasts treated with 27P silk or 10 ng / mL TGF-B for 24h. FIG.109B: Quantification of %ɑSMAHighcells showed no significant induction of SMA protein expression with 27P silk treatment or silk and VC combination. TGF-B strongly induced ɑSMA expression by 4-fold. FIG.109C: mRNA levels of fibrosis-associated markers, ɑSMA and TGF-B show no significant effects with 27P silk treatment and strong induction with TGF-B treatment for 24h and 6h, respectively. FIG.110A and FIG.110B show 27P silk treatment does not induce inflammatory markers in 2D culture. FIG.110A: mRNA expression of pro- inflammatory markers, IL6, IL8, IL17 and MMP2 after 6h of 27P silk treatment showed potential decreases with IL17 and MMP2 and no significant induction with IL6 and IL8. FIG.110B: Secreted IL6 protein measured by ELISA remained undetected with 6h and 24h 27P silk treatments while IL6 secretion was strongly induced by RA and TGF-B treatments. FIG.111 illustrates hypothesis and model for mechanism of action of 27P silk peptides.27P silk peptides penetrate through intact skin barrier (epidermis) to directly bind papillary fibroblasts with specificity. Direct binding of 27P silk peptides to papillary fibroblasts induces higher extracellular translocation of CD44 receptors allowing higher silk binding to induce increased Col1 secretion and processing to maintain ECM homeostasis, without inducing fibrosis or inflammatory markers. FIG.112 depicts specific silk binding of 27P silk peptides to dermal fibroblast cells. Quantification of intensity of labeled-27P silk peptides binding to fibroblasts and background area, representing non-specific binding. FIG.113A and FIG.113B depict 27P silk biochemically interacts with recombinant CD44 and does not alter CD44 mRNA in 2D cell culture. FIG.113A: CD44 mRNA levels show no significant changes with 6h and 24h of 27P silk treatment, while CD44 mRNA decreased with VC, TGF-B, RA and HA after 6h. FIG. 113B: ELISA assay showing specific interaction of 27P silk with recombinant CD44 protein. FIG.114 depicts mRNA expression of HSP47 (pro-Col1A1 chaperone protein) after 6h, 24h 27P silk treatment shows no significant changes compared to mock samples. FIG.115 shows 27P silk peptides do not induce collagens through transcriptional regulation. mRNA expression of Col1A1, Col3A, MMP1 and VIM after 6h and 24h 27P silk treatments show no significant changes, directly indicating lack of transcriptional regulation of collagens by silk. FIG.116 illustrates a schematic overview of method development for silk receptor discovery. A: Total protein of Human tissue lysates (for example, skin or colon tissue lysates) are uploaded onto SDS-PAGE to separate the proteins into distinct bands based on their molecular weight. Then, part of the gel is stained with Coomassie stain to visualize the protein bands, and some is blotted on PVDF membrane for a Far Western Blot analysis. During the Far Western Blot analysis, the membrane is incubated with biotinylated silk to allow interactions with potential receptors. B: The Far Western Blot membrane that was labeled with biotinylated silk, and the Coomassie-stained gel, are compared carefully, and bands in the Coomassie gel that share the exact molecular weight as the silk-binding bands in the blot are excised from the gel, and analyzed by LC / MS. Once the proteins of interest are identified by LC / MS, a second Far Western Blot is performed with the recombinant purified potential silk-binding proteins for validation of silk binding. Lane 1 – tissue lysate labeled with biotinylated silk; lane 2 – a single, purified protein that was identified as a potential silk-binding protein. This purified protein corresponds to the protein identified by LC / MS in the upper band of the Far Western Blot of the tissue lysates (Lane 1). The purified protein is labeled with biotinylated silk in Far Western Blot; lane 3 - a single, purified protein that was identified as a potential silk-binding protein. This purified protein corresponds to the protein identified by LC / MS in the lower band of the Far Western Blot of the tissue lysates (Lane 1). The purified protein is labeled with biotinylated silk in Far Western Blot. In lane 1, bands that did not bind silk are colored in black to clarify the specificity of the assay and are not visible in the actual Far Western Blot. FIG.117 depicts SDS polyacrylamide gel electrophoresis of cell and tissue lysates. Cells of Ker-CT cell line were lysed, and total protein content was determined. Total protein of skin and colon tissue lysates were purchased from BioChain®. Each lane contains 20 µg of total protein for each lysate. Cell and tissue lysates were loaded side by side to compare their proteomes. The gel was stained with Coomassie stain. Ker – Ker-CT cell line. FIG.118 depicts specific silk binding to potential targets analyzed by Far Western Blot.10 µg of Keratinocyte (KerCT) cell line lysate, and total protein from skin and colon lysates were loaded onto SDS-PAGE, separated, and transferred onto a PVDF membrane for further labeling. Membranes were incubated with biotinylated Low Skid (LS-biotin). The following step was incubation with streptavidin conjugated to HRP. Addition of HRP substrate and exposure of the membrane revealed silk binding to specific bands. FIG.119 depicts identification of potential silk-binding proteins in cell and tissue lysates by combining SDS-PAGE and Far Western Blot. Cell lysates of keratinocytes cell line Ker-CT and total protein of skin and colon tissue lysates were run on an SDS-PAGE and were stained with Coomassie or blotted on a PVDF membrane for labeling with silk (Far Western Blot). The SDS-PAGE and the blot were compared, and bands on the SDS-PAGE that matched silk-binding bands on the blot were excised and analyzed by LC / MS. The excised bands are labeled by numbers 11-14 and highlighted by asterisks (*) on the blot and the SDS-PAGE. Ker – Ker-CT cell line (keratinocytes). FIG.120A and FIG.120B depict Far Western Blot and Coomassie-blue SDS- PAGE of purified Keratin 1 and Keratin 10 with biotinylated silk. FIG.120A: Far Western Blot and Western Blot of Keratin 1, Keratin 10, and BSA. Following identification of potential silk-binding proteins by LC / MS, a Far Western Blot with purified proteins identical to the potential target proteins identified in the lysates was performed to validate their interaction with biotinylated Low Skid silk. Purified Keratin 1 (KRT1), Keratin 10 (KRT10), and Bovine Serum Albumin (BSA) as a negative control were loaded onto SDS-PAGE and were transferred to a PVDF membrane for Western blot or Far Western Blot analysis. The membranes were labeled with biotinylated Low Skid silk (LS), biotinylated Mid Skid silk, or anti-His- tag conjugated to HRP (KRT1 and KRT10 are His-tagged) (1 µg protein in each lane). FIG.120B: SDS-PAGE stained with Coomassie blue of KRT1, KRT10, and BSA (4 µg protein in each lane). Estimated molecular weights of the target proteins: KRT1 – 67 kDa; KRT10 – 62.8 kDa; BSA – 66.4 kDa. FIG.121A and FIG.121B show different silk formulations support the growth of skin / probiotic bacteria at different concentrations. Growth of M. luteus (FIG. 121A) (19h), L. plantarum and L. rhamnosus (FIG.121B) (40h) in Low and Mid Skid formulations. In the graph the optical density at 600nm [OD600nm] of the samples containing bacterial cells is presented after the subtraction of the background OD600nm. FIG.122A and FIG.122B show Loq Skid silk and Q-Elution from Low Skid silk support the growth of normal skin microbiome and probiotic bacteria. Growth of M. luteus (FIG 122A) (19h), L. plantarum and L. rhamnosus (FIG.122B) (40h) in Low and Mid Skid formulations. In the graph the optical density at 600nm [OD600nm] of the samples containing bacterial cells is presented after the subtraction of the background OD600nm. FIG.123 illustrates a schematic of the protocol we followed to separate the cytoplasmic membranes from the cytosolic components from M. luteus. FIG.124A and FIG.124B show isolation of M. luteus cytosolic and membrane fractions. FIG.124A: Coomasie staining of proteins from the cytosolic and membrane fractions from M. luteus. FIG.124B: staining of the same gel as in A with anti-LTA antibody. FIG.125 shows Low Skid silk interacts with membrane and peripherally associated with the membrane proteins in bacteria. Left panel, coomasie stained protein bands from a membrane fraction from M. luteus. Middle panel, protein bands on which biotinylated Low Skid silk binds. Right panel, protein bands excised and analyzed in an LC / MS for protein identification. FIG.126A and FIG.126B depict a schematic overview of method development for silk receptor discovery. FIG.126A shows Human cells (for example, keratinocytes or fibroblasts) are lysed to create whole cell lysate that contains the full proteome of the cells. The whole cell lysate is uploaded onto SDS-PAGE to separate the proteins into distinct bands based on their molecular weight. Then, part of the gel is stained with Coomassie stain to visualize the protein bands, and some is blotted on PVDF membrane for a Far Western Blot analysis. During the Far Western Blot analysis, the membrane is incubated with biotinylated silk to allow interactions with potential receptors. FIG.126B shows the Far Western Blot membrane that was labeled with biotinylated silk, and the Coomassie-stained gel, are compared carefully, and bands in the Coomassie gel that share the exact molecular weight as the silk- binding bands in the blot are excised from the gel, and analyzed by LC / MS. Once the proteins of interest are identified by LC / MS, the Far Western Blot (with biotinylated silk) is performed side-by-side with a standard western blot, using specific antibodies against the identified proteins to validate they share the same molecular weight. Lane 1 – cell lysate labeled with biotinylated silk; lane 2 - cell lysate labeled with a specific antibody that corresponds to the protein identified by LC / MS in the upper band of the Far Western Blot; lane 3 - cell lysate labeled with a specific antibody that corresponds to the protein identified by LC / MS in the lower band of the Far Western Blot. In lane 1, bands that did not bind silk are colored in black to clarify the specificity of the assay, and are not visible in the actual Far Western Blot. FIG.127 illustrates SDS polyacrylamide gel electrophoresis of cell lysates. Cells of Ker-CT cell line and primary fibroblasts were lysed, and total protein content was determined. Each lane contains 20 µg of total protein for each lysate. Cell lysates were loaded side by side to compare the proteomes of the two cell types. The gel was stained with Coomassie stain. Ker – Ker-CT cell line. FIG.128 illustrates specific silk binding to potential targets analyzed by Far Western Blot. Keratinocyte (KerCT cell line) lysate was loaded onto SDS-PAGE, separated, and transferred onto a PVDF membrane for further labeling. Membranes were incubated with either a specific antibody against CD44 (anti-CD44), 1500 kDa biotinylated Hyaluronic acid (HA), biotinylated Low Skid (LS-biotin), or biotinylated Mid Skid (MS-biotin). The following step was incubation with either a secondary antibody (for anti-CD44 labeling) conjugated to HRP (horseradish peroxidase), or streptavidin conjugated to HRP (for HA and biotinylated silk). Addition of HRP substrate and exposure of the membrane revealed silk binding to specific bands, and Hyaluronic acid binding to CD44 (positive control to show that proteins are capable of refolding after SDS removal and can bind their specific ligands). FIG.129A and FIG.129B illustrates identification of potential silk-binding proteins in cell lysates by combining SDS-PAGE and Far Western Blot. FIG.129A shows identification of potential silk-binding proteins in keratinocytes. Cell lysates of keratinocytes cell line Ker-CT were run on an SDS-PAGE and were stained with Coomassie or blotted on a PVDF membrane for labeling with silk (Far Western Blot). The SDS-PAGE and the blot were compared, and bands on the SDS-PAGE that matched silk-binding bands on the blot were excised and analyzed by LC / MS. The excised bands are labeled by numbers 1-6 and highlighted by asterisks (*) on the blot and the SDS-PAGE. FIG.129B shows identification of potential silk-binding proteins in fibroblasts. Cell lysates of primary fibroblasts and Ker-CT cell line (as a reference) were run on an SDS-PAGE and were stained with Coomassie or blotted on a PVDF membrane for labeling with silk (Far Western Blot). The SDS-PAGE and the blot were compared, and bands on the SDS-PAGE that matched silk-binding bands on the blot were excised and analyzed by LC / MS. The excised bands are labeled by numbers 7-9 and highlighted by asterisks (*) on the blot and the SDS-PAGE. LS-biotin – biotinylated Low Skid silk; Ker – Ker-CT cell line (keratinocytes). FIG.130 illustrates labeling of silk-binding target proteins by specific antibodies. Following identification of potential silk-binding proteins by LC / MS, the potential target proteins were labeled with specific antibodies to validate their molecular weight and relative position on a blot compared to Far Western Blot with biotinylated Low Skid silk. Cell lysates of keratinocytes (Ker-CT cell line) were loaded onto SDS-PAGE and were either stained with Coomassie stain or transferred to a PVDF membrane for Western blot or Far Western Blot analysis. The membranes were labeled with biotinylated Low Skid silk (LS), anti-keratin Type II cytoskeletal 5 (Ker5), anti-protein disulfide isomerase (PDI), or anti-annexin A2. Bands that correspond to Ker5, PDI, and Annexin A2 are highlighted by an asterisk (*). Estimated molecular weights of the target proteins: Ker5 – 62.37 kDa; PDI – 57.11 kDa; Annexin A2 – 38.6 kDa. While the above-identified drawings set forth presently disclosed embodiments, other embodiments are also contemplated, as noted in the discussion. This disclosure presents illustrative embodiments by way of representation and not limitation. Numerous other modifications and embodiments can be devised by those skilled in the art which fall within the scope and spirit of the principles of the presently disclosed embodiments. DETAILED DESCRIPTION The disclosure provides a method of treatment or prevention of a disorder, disease, or condition in a subject in need thereof, the method comprising administering to the subject a composition comprising fibroin fragments, wherein the fibroin fragments comprise a plurality of modified fibroin fragments. In aspects, the composition for use in the treatment or prevention of a disorder, disease, or condition in a subject in need thereof, comprising fibroin fragments, wherein the fibroin fragments comprise a plurality of modified fibroin fragments. The disclosure is related to a new silk-based platform including the development of the platform for identifying new silk's interaction with various cell receptors and proteins and enabling the development of targeted therapies. The new silk-based platform disclosed herein identifies silk interaction with various cell receptors and proteins, enabling the development of targeted therapies. Key Proteins Identified to Interact with the new silk-based platform include, but are not limited by: (1) CD44: A receptor crucial for cell adhesion and migration. CD44 interacts with new silk in the platform and plays a significant role in cancer metastasis and inflammation; (2) Annexin A2: Involved in cell membrane repair and anti- inflammatory responses, Annexin A2 is another key protein identified to interact with new silk; (3) Keratin 5, Keratin 1, and Keratin 10: Important markers for keratinocyte differentiation, all shown to interact with new silk in the platform; (4) Protein Disulfide Isomerase (PDI): An enzyme involved in protein folding and maintaining cellular homeostasis, which is found to interact with new silk in the platform. Therapeutic Development for CD44 Key Roles of CD44 include: (1) Cell Adhesion and Migration: CD44 binds to hyaluronic acid (HA) in the extracellular matrix, facilitating cell movement and adhesion. This function is essential in cancer metastasis, where CD44 aids tumor cell migration and invasion. (2) Cancer Stem Cells (CSCs): CD44 is highly expressed in cancer stem cells, making it a marker for identifying CSCs. Targeting CD44 could help eliminate CSCs, which are often resistant to conventional therapies and responsible for tumor recurrence. (3) Drug Resistance: CD44 interacts with signaling pathways like PI3K / Akt and MAPK, contributing to cancer cell survival and resistance to chemotherapy and radiation. Inhibiting CD44 may help overcome drug resistance in cancer treatment. (4) Inflammation and Immune Modulation: CD44 modulates immune cell function, particularly in T cells and macrophages, playing a role in inflammatory responses. This makes CD44 a target for treating autoimmune and inflammatory diseases. CD44 as a Drug Target and New silk as a therapeutic intervention: (1) Monoclonal Antibodies: Monoclonal antibodies targeting CD44 have been developed, particularly for cancers, to block the CD44-HA interaction, reducing tumor adhesion and migration. New silk peptides can also disrupt CD44-HA interactions, offering a novel mechanism to inhibit this binding. (2) CD44-Hyaluronan Inhibitors: Small molecules or peptides designed to disrupt CD44-HA binding could block cancer invasion and metastasis. New silk-specific peptides could serve as inhibitors, making them useful in anti-metastatic strategies. (3) Nanoparticle Delivery Systems: CD44 is a target for drug-loaded nanoparticles. Since CD44 is overexpressed in many cancers, nanoparticles conjugated with CD44 ligands can deliver drugs directly to tumor cells. New silk peptides can be engineered to target CD44-overexpressing cells, enhancing treatment precision and efficacy. (4) CD44-Specific Immunotherapy: New silk antibody conjugates can be engineered to selectively destroy CD44-expressing cancer cells. These new silk-based systems can target CD44 overexpression in hematological cancers and solid tumors. (5) Inflammation and Immune Modulation by New silk and New silk-Derived Peptides: CD44 plays a role in immune modulation and inflammation. New silk peptides may modulate CD44-related immune responses, offering potential treatments for inflammatory conditions. Examples of Inflammatory conditions Involving CD44 include: (1) Rheumatoid Arthritis (RA): CD44 promotes immune cell infiltration in synovial tissue, exacerbating inflammation. Targeting CD44 could reduce immune cell infiltration and joint inflammation; (2) Inflammatory Bowel Disease (IBD): CD44 overexpression in inflamed mucosa contributes to immune cell trafficking and tissue damage. CD44-targeting therapies could reduce inflammation by interfering with immune cell adhesion; (3) Systemic Lupus Erythematosus (SLE): CD44 mediates T cell and monocyte migration, contributing to chronic inflammation. Blocking CD44 could reduce immune cell infiltration in organs affected by lupus; (4) Multiple Sclerosis (MS): CD44 mediates T cell migration across the blood-brain barrier, contributing to CNS inflammation. Targeting CD44 could limit immune cell invasion and reduce myelin damage; (5) Psoriasis: CD44 promotes keratinocyte proliferation and immune cell recruitment to the skin. CD44-targeted therapies could reduce inflammation in psoriatic lesions; (6) Asthma: CD44 recruits eosinophils and T cells to airway mucosa, contributing to inflammation. Targeting CD44 could reduce airway inflammation and improve asthma control. Examples of Neurodegenerative Conditions Involving CD44 include: (1) Alzheimer’s Disease (AD): CD44 is involved in neuroinflammation and immune cell recruitment to the CNS, contributing to neuronal damage. Targeting CD44 could modulate neuroinflammatory responses, reduce amyloid-beta accumulation, and improve neuronal survival; (2) Multiple Sclerosis (MS): In MS, CD44 mediates T cell migration across the blood-brain barrier (BBB), contributing to inflammatory attacks on myelin. Targeting CD44 could limit immune cell infiltration into the CNS, reducing myelin damage and disease progression. (3) Parkinson’s Disease (PD): CD44 is linked to neuroinflammatory responses in PD. Modulating CD44 activity could reduce inflammation-mediated neuronal death, which is a key factor in the progression of PD. (4) Amyotrophic Lateral Sclerosis (ALS): CD44 expression has been implicated in the inflammatory response in ALS, particularly in motor neuron degeneration. Targeting CD44 could slow ALS progression by reducing inflammation and promoting neuronal survival. Examples of Metabolic Conditions Involving CD44 include: (1) Obesity and Type 2 Diabetes: CD44 is implicated in adipose tissue inflammation and insulin resistance, key factors in metabolic disorders such as obesity and type 2 diabetes. Targeting CD44 could help modulate metabolic inflammation and improve insulin sensitivity, providing a novel therapeutic strategy for metabolic diseases. (2) Non- Alcoholic Fatty Liver Disease (NAFLD): CD44 is involved in hepatic inflammation and fibrosis in NAFLD. Inhibiting CD44 could reduce liver inflammation and the progression of fibrosis in patients with NAFLD. Examples of Gut-Related Conditions (e.g., Inflammatory Bowel Disease and Intestinal Permeability): (1) CD44 is involved in immune cell migration and inflammation in the gut, playing a role in conditions such as inflammatory bowel disease (IBD), Crohn's disease, and ulcerative colitis. (2) Targeting CD44 in the gut could help reduce intestinal inflammation, promote gut barrier repair, and improve outcomes in patients with conditions associated with intestinal permeability or gut inflammation. Examples of Skin-Related Diseases Involving CD44 include: (1) Atopic Dermatitis (AD): CD44 plays a role in immune cell recruitment and skin inflammation in atopic dermatitis. Targeting CD44 could help reduce inflammatory responses and support skin barrier repair, improving symptoms such as itching, redness, and dryness in AD patients. (2) Psoriasis: CD44 is involved in keratinocyte proliferation and immune cell recruitment in psoriatic lesions. Inhibiting CD44 could help reduce the hyperproliferation of skin cells and immune-mediated inflammation, providing relief from the scaly patches and inflammation associated with psoriasis. (3) Chronic Wounds and Skin Ulcers: In conditions where wound healing is impaired, such as diabetic ulcers and venous leg ulcers, CD44 is involved in cell migration and tissue repair. Targeting CD44 may help promote cell adhesion, enhance wound healing, and reduce chronic inflammation in these wounds. (4) Skin Cancer (e.g., Melanoma): CD44 is overexpressed in melanoma and other skin cancers, where it aids in tumor cell migration and invasion. Targeting CD44 in skin cancers may inhibit tumor growth and prevent metastasis by reducing cell adhesion and invasion of cancer cells. (5) Contact Dermatitis: In allergic or irritant contact dermatitis, CD44 is involved in the recruitment of immune cells to the skin, leading to localized inflammation and rash formation. Inhibiting CD44 could reduce immune cell infiltration and alleviate symptoms such as redness, itching, and blistering. Annexin A2 as a Drug Target: (1) Monoclonal Antibodies: Annexin A2 is overexpressed in various cancers, inflammatory conditions, neurodegenerative diseases, and metabolic disorders. It plays a role in cell membrane repair, signal transduction, fibrinolysis, and tumor progression. Monoclonal antibodies targeting Annexin A2 can interfere with its interaction with key proteins like plasminogen, reducing cancer cell invasion and migration, and potentially preventing neuronal damage in neurodegenerative diseases. New silk peptides could potentially disrupt Annexin A2-related interactions by stabilizing or inhibiting its membrane-binding abilities, offering therapeutic potential in cancer, metabolic disorders, inflammation, and neurodegeneration. (2) Annexin A2 Inhibitors: Small molecules or peptides can inhibit Annexin A2’s role in membrane repair, fibrinolysis, and tumor growth, potentially halting cancer metastasis, inflammation spread, neuronal damage, and metabolic dysregulation. New silk-based peptides could serve as inhibitors by disrupting Annexin A2’s membrane association, blocking its pathological activity in cancer, inflammation, neurodegenerative diseases, and metabolic disorders such as diabetes and obesity. (3) Nanoparticle Delivery Systems: Annexin A2 is overexpressed on cancer cells, inflamed tissues, damaged neurons, and metabolically active tissues. Drug-loaded nanoparticles targeting Annexin A2 can deliver therapeutic agents directly to these cells, improving treatment precision and efficacy. New silk peptides can be functionalized as targeting ligands on nanoparticles, directing therapeutic payloads to Annexin A2-expressing cells in cancer, inflammation, neurodegeneration, and metabolic diseases. (4) Annexin A2-Specific Immunotherapy: Annexin A2 is implicated in immune modulation, tumor immunity, neuroinflammation, and metabolic regulation. Targeted immunotherapies involving Annexin A2-specific antibodies could selectively destroy Annexin A2-expressing cancer cells or modulate immune and inflammatory responses in neurodegenerative and metabolic conditions. New silk antibody conjugates targeting Annexin A2 could enhance the specificity of cancer immunotherapy or help modulate inflammation, tumor immunity, and metabolism by regulating Annexin A2 activity in immune and metabolic cells. (5) Cancer, Inflammation, Neurodegeneration, and Metabolic Modulation: Annexin A2 plays a critical role in tumor progression, immune responses, neuronal repair, and metabolic regulation. It is a key player in cancer, inflammation, neurodegeneration, and metabolic dysregulation, making it a promising target for treating cancers, autoimmune diseases, neurodegenerative conditions, and metabolic disorders. New silk peptides could be designed to modulate Annexin A2’s role in tumor growth, immune function, neuronal protection, and metabolic processes, providing therapeutic benefits in conditions like rheumatoid arthritis, systemic lupus erythematosus, Alzheimer’s disease, diabetes, obesity, and various cancers. Examples of Conditions Involving Annexin A2 include: (1) Cancer: Annexin A2 is overexpressed in many cancers, where it promotes tumor progression, angiogenesis, metastasis, and inflammation. Targeting Annexin A2 in cancers like breast cancer, lung cancer, colorectal cancer, and glioblastoma could reduce tumor growth, invasion, and metastasis. (2) Rheumatoid Arthritis (RA): Annexin A2 is linked to macrophage activity and joint inflammation. Targeting it could reduce inflammation in RA by inhibiting immune cell activation. (3) Inflammatory Bowel Disease (IBD): Annexin A2 expression is elevated in inflamed intestinal tissues, contributing to immune cell recruitment. Inhibiting Annexin A2 may reduce inflammation and tissue damage in IBD. (4) Systemic Lupus Erythematosus (SLE): Annexin A2 is implicated in autoimmune responses in SLE. Targeting Annexin A2 could help reduce immune-mediated tissue damage. (5) Alzheimer’s Disease (AD): Annexin A2 is involved in neuronal repair and neuroinflammation in Alzheimer’s. Targeting it could help reduce inflammation and protect neurons from damage. (6) Diabetes and Obesity: Annexin A2 is implicated in metabolic regulation, particularly in insulin signaling and lipid metabolism. Targeting Annexin A2 could improve insulin sensitivity and modulate lipid metabolism, offering potential treatments for diabetes and obesity. (7) Cancer-Associated Inflammation: Annexin A2 promotes inflammation and tumor progression in cancers. Targeting it could suppress cancer- related inflammation and metastasis. Labeled New silk for Diagnostic, Visualization: and Targeting therapeutic Labeled New silk for Diagnostic, Visualization: and Targeting therapeutics: (1) New silk Labeling: New silk peptides can be labeled with imaging agents such as fluorescent dyes, radioisotopes, or contrast agents (used in MRI, PET, or CT scans). These labeled new silk peptides will specifically bind to CD44 receptors, which are overexpressed on the surface of cancer cells in tumors. (2) CD44 Targeting: CD44 is a well-known marker for cancer stem cells and is often overexpressed in various aggressive tumor types such as breast cancer, lung cancer, colorectal cancer, and glioblastoma. By functionalizing new silk peptides to target CD44, the new silk can localize to tumor sites where CD44 is highly expressed and better direct the radiation therapy. (3) Diagnostic Visualization: Once the labeled new silk peptides bind to the tumor's CD44 receptors, the imaging agents attached to the new silk will enable non- invasive visualization of the tumor. The method could be used with fluorescence imaging, MRI, or PET / CT scans, depending on the imaging agent chosen. (4) Enhanced Imaging for Diagnostics: This new silk-CD44 targeting system enhances the specificity and clarity of tumor imaging by focusing on areas with high CD44 expression. This approach can help diagnose and monitor tumor progression, improving detection and possibly aiding in personalized treatment plans for cancers with high CD44 expression. Self-Assembling new silk Self-Assembling new silk: New silk peptides can self-assemble, which can be leveraged for both therapeutic and diagnostic purposes. Non-labeled new silk can be utilized as a therapeutic agent, while labeled new silk can be used for diagnostic imaging or visualization of the therapeutic new silk in action. Amino Acid Composition of Labeled Silk and Traceability in Blood Amino Acid Composition of Labeled Silk and Traceability in Blood: (1) Silk Peptide Labeling: Silk peptides can be functionalized or labeled with tracers such as fluorescent markers, radioisotopes, or metabolic labels to monitor their circulation and distribution in the body. When labeled silk is introduced therapeutically, its amino acid composition could be tracked in the bloodstream, allowing for precise monitoring of its biodistribution and metabolism. (2) Amino Acid Composition and Bioavailability: Silk peptides are composed of amino acids like glycine, alanine, and serine. These amino acids are naturally occurring in the body, and the breakdown of silk peptides could contribute to systemic amino acid pools. By labeling the amino acids or the silk peptide backbone, the degradation products of silk could be traced, providing insights into their metabolism and bioavailability in blood plasma. (2) Applications in Diagnostics and Therapeutics: Labeled silk could serve as a biomarker for tracking the effectiveness of therapeutic silk, such as in atopic dermatitis, gut health, or cancer therapies. Blood plasma analysis could reveal the presence of labeled amino acids from silk breakdown, offering a non-invasive way to assess therapeutic distribution, absorption, and clearance. (3) Monitoring Metabolic Pathways: The ability to trace labeled silk’s amino acids in blood could also provide insights into metabolic pathways and the long-term biocompatibility of therapeutic silk formulations. This traceability could be especially useful in ensuring the safety and efficacy of silk-based treatments, particularly for chronic conditions like cancer, gut disorders, or skin diseases. In some embodiments, the disease, disorder or condition is selected from Atopic Dermatitis (Eczema), Psoriasis (e.g., plaque psoriasis), Contact Dermatitis, rosacea, acne (e.g., cystic acne), Ichthyosis (e.g., ichthyosis vulgaris), inflammation, Netherton Syndrome (a genetic disorder that lead to chronic skin inflammation and increased susceptibility to an infection), Xerosis (Dry Skin), Aging Skin, impaired wound healing, Diabetic Dermopathy, Pruritus, Scleroderma, Multiple Sclerosis (MS), Bacterial and fungal Infection, abnormal scarring condition, dysbiosis, autoimmune condition like lupus, Systemic Lupus Erythematosus, and / or rheumatoid arthritis. In some embodiments, the disease, disorder or condition is a chronic skin condition. In some embodiments, the chronic skin condition is eczema (e.g., atopic dermatitis), psoriasis (e.g., plaque psoriasis), dermatitis (e.g., contact dermatitis), rosacea, acne (e.g., cystic acne), ichthyosis (e.g., ichthyosis vulgaris), or inflammation. In some embodiments, the disease, disorder or condition is one or more of wrinkling, sagging, thin, dry, or unevenly pigmented skin, impaired wound healing or chronic inflammation. In some embodiments, the condition comprises a skin or dermatological condition. In some embodiments, the dermatological condition is atopic dermatitis. In some embodiments, the disease, disorder or condition is dysbiosis. In some embodiments, the disorder, disease, or condition is an inflammatory disease, disorder or condition. In some embodiments, the inflammatory disease, disorder or condition is Rheumatoid Arthritis, Inflammatory Bowel Disease, Systemic Lupus Erythematosus, Multiple Sclerosis (MS), Psoriasis, Asthma, allergic rhinitis, asthma, food allergy, or another autoimmune condition. In some embodiments, the disease, disorder or condition is inflammatory bowel disease (IBD), Intestinal Permeability, Crohn's disease, ulcerative colitis, celiac disease, irritable bowel syndrome (IBS), NASH, cirrhosis, metabolic disorders, or another disease, disorder or condition involving regulation of a gut epithelial cell. In some embodiments, the disease, disorder or condition is a neurodegenerative condition. In some embodiments, the neurodegenerative condition is Alzheimer’s Disease (AD), Multiple Sclerosis (MS), Parkinson’s Disease (PD), or Amyotrophic Lateral Sclerosis (ALS). In some embodiments, the disease, disorder or condition is a metabolic condition. In some embodiments, the metabolic condition is obesity and / or type 2 Diabetes, or non- alcoholic fatty liver disease (NAFLD). In some embodiments, the disease, disorder or condition is a cancer. In some embodiments, the cancer is melanoma. In some embodiments, the disease, disorder or condition is associated with dysregulation in a gut barrier and / or in a tight junction of the gut. In some embodiments, the silk fibroin fragment interacts with lipoteichoic acid, lipomannan, a TLR-2 receptor, or a protein kinase. In some embodiments, the protein kinase is a Tyrosine-protein kinase. In embodiments, the fibroin fragment binds to a protein disulfide isomerase (PDI), a CD44 receptor, Annexin A2, Keratin 5, Keratin 1, or Keratin 10. In some embodiments, the fibroin fragment binds to a CD44 receptor. In some embodiments, the disease, disorder, or condition is alleviated by decreasing the secretion of TNF-α and IL-6, and / or increasing secretion of IL-10. In some embodiments, the disease, disorder, or condition is alleviated by modulating Annexin A2’s role in tumor growth, immune function, neuronal protection, and / or metabolic processes. In some embodiments, the disorder, disease, or condition is alleviated by stimulating or modulating a skin barrier-specific protein in a subject in need thereof. In some embodiments, the skin barrier-specific protein is differentially regulated. In some embodiments, the skin barrier-specific protein comprises at least one of desmoplakin (DSP), cystatin A (CSTA), tumor-associated calcium signal transducer 2 (TACSTD2), biglycan (BGN), decorin (DCN) and / or epiplakin 1 (EPPK1). In some embodiments, at least one of desmoplakin (DSP), cystatin A (CSTA) and / or tumor- associated calcium signal transducer 2 (TACSTD2) is upregulated post- administration. In some embodiments, at least one of biglycan (BGN), decorin (DCN) and / or epiplakin 1 (EPPK1) is downregulated post-administration. In some embodiments, at least one of the skin barrier-specific protein is a tight junction protein. In some embodiments, the fibroin fragment binds to a skin epithelial cell and / or induces upregulation of the tight junction protein. In some embodiments, the tight junction protein is Claudin-1, occludin, or Zo1. In some embodiments, the tight junction protein is Claudin-1 expressing in a human epidermal keratinocyte. In some embodiments, Claudin-1 is expressed in a human epidermal keratinocyte. In some embodiments, a claudin-1 level is promoted, increased, or restored post- administration in the epidermal keratinocyte. In some embodiments, the epidermal keratinocyte is an h-TERT immortalized keratinocyte. In some embodiments, the epidermal keratinocyte is a primary human keratinocyte. In embodiments, administering the composition promotes a growth of a normal skin microbiome and a probiotic bacteria. In some embodiments, the fibroin fragment interacts with a receptor on a probiotic bacteria surface to promote the growth of the probiotic bacteria. In some embodiments, the probiotic bacteria is selected from Micrococcus luteus, Lactiplantibacillus plantarum, and Lacticaseibacillus rhamnosus. In some embodiments, administering the composition improves the function of a skin keratinocyte and a fibroblast. In embodiments, administering the composition promotes skin barrier function, regulates immune responses, and / or confers pathogen bacteria colonization resistance. In some embodiments, the fibroin fragment penetrates an intact skin barrier and binds to a dermal fibroblast. In some embodiments, administering the composition induces de novo collagen synthesis, secretion and / or increases extracellular matrix deposition. In some embodiments, administering the composition induces secretion of pro-Col1A1, Col3A, and / or ɑ- SMA. In embodiments, administering the composition induces secretion of pro- Col1A. In some embodiments, the silk fibroin fragment accelerates skin barrier regeneration by promoting expression of the tight junction protein. In some embodiments, the fibroin fragment enhances keratinocyte differentiation and / or Filaggrin maturation. In some embodiments, the fibroin fragment increases expression and maturation of Involucrin and / or Filaggrin A. In some embodiments, the fibroin fragment binds to a corneal keratin selected from Keratin 1 and Keratin 10. In some embodiments, the fibroin fragment induces a switch from a basally-expressed keratin (e.g. K5, K14) to a suprabasally-expressed keratin (e.g. K1, K10). In some embodiments, the fibroin fragment enters the skin and binds selectively to the CD44 receptor on a stratum basale cell. In some embodiments, the KDF polypeptide binds to an undifferentiated keratinocyte in the skin and accelerates keratinocyte differentiation to accelerate skin barrier regeneration. In some embodiments, the composition maintains skin extracellular matrix (ECM) homeostasis. In some embodiments, the fibroin fragment is a keratinocyte differentiation factor (KDF) polypeptide. In some embodiments, the KDF polypeptide enhances keratinocyte differentiation and / or Filaggrin maturation. In some embodiments, the KDF polypeptide increases expression and maturation of Involucrin and / or Filaggrin A. In some embodiments, the tight junction protein is selected from Claudin-1 and Occludin. In some embodiments, the KDF polypeptide binds to a corneal keratin selected from Keratin 1 and Keratin 10. In some embodiments, the KDF polypeptide induces a switch from a basally-expressed keratin (e.g. K5, K14) to a suprabasally- expressed keratin (e.g. K1, K10). In some embodiments, the KDF polypeptide enters the skin and binds selectively to the CD44 receptor on a stratum basale cell. In some embodiments, the KDF polypeptide binds to an undifferentiated keratinocyte in the skin and accelerates keratinocyte differentiation to accelerate skin barrier regeneration. In some embodiments, the composition maintains skin extracellular matrix (ECM) homeostasis. In some embodiments, the subject in need experiences reduced erythema post-administration. In some embodiments, the subject in need experiences decreased transepidermal water loss post-administration. In some embodiments, the subject in need experiences a reduced eczema lesion count post- administration. In some embodiments, the subject in need experiences reduced edema post-administration. In some embodiments, the subject in need experiences reduced rhytids post-administration. In some embodiments, the subject in need experiences increased skin hydration post-administration. In some embodiments, the subject in need experiences increased skin firmness post-administration. In some embodiments, the subject in need experiences a reduced sign of skin inflammation post- administration. In some embodiments, the subject in need experiences a reduced sign of aging skin post-administration. In some embodiments, the composition is administered in combination with vitamin C. In some embodiments, administering the composition in combination with vitamin C synergistically increases pro-Col1A1 secretion. In some embodiments, the composition is administered parenterally. In some embodiments, the composition is formulated as a topical composition. The disclosure provides potential treatments for skin diseases. Skin diseases include Psoriasis, Eczema, Lupus Erythematosus, Rheumatoid Arthritis, Contact Dermatitis, or Diabetic Dermopathy. Silk-based products and formulations have shown benefits for individuals with eczema in human clinical trials. In clinical trial settings, improvement in a number of eczema lesion, skin hydration and reduction in redness were observed that are essential in managing eczema symptoms. The disclosure provides potential treatments for wound healing. Silk and its different formulations adhere to skin biopsy in both multicellular and single-cell models. The disclosure provides treatments which target specific receptors on cells. Silk has the ability to mimic HA (Hyaluronic Acid) in inducing anti-inflammatory effects by potentially binding to the CD44 receptor on macrophages. The compositions of the disclosure can be used in wound dressings, drug delivery, implantable devices, nerve regeneration, or tissue and organ transplantation. Tissue Engineering Scaffolds: Silk scaffolds facilitate tissue regeneration and repair by providing a supportive structure for cells to grow and organize, especially in applications like skin grafts and cartilage repair. Silk materials can act as carriers for drug delivery, gradually releasing therapeutic agents to the targeted site, making it beneficial for localized treatments. Silk's biocompatibility makes it suitable for creating implantable medical devices, such as nerve conduits and vascular grafts, enhancing biointegration and reducing the risk of adverse reactions. Silk-based nerve conduits support nerve regeneration, providing a suitable environment for nerve growth and repair after injuries. Silk can serve as a preservation matrix for transplantable tissues and organs, maintaining their viability and functionality during storage and transportation. The disclosure provides peptides that target specific receptors on different cell types. Potenshal to modulate the signaling of the receptor as well as to deliver other drugs treatments (cytokinese, chemotherapy molecules, small molecules, antibodies ...). The disclosure provides potential drug, and drug delivery system. The potential discovery of specific silk peptides capable of binding to CD44 and other receptors (TLR4, TLR2) holds promise as a versatile platform to target these and other receptors in various diseases. These peptides have the potential to be conjugated with various therapeutic antibodies, cytokines, and small molecules, expanding their applicability and enhancing their therapeutic effects in different treatments. The disclosure provides potential to targeting pattern recognition receptors (TLR4, TLR2) modulating the signaling and / or delivering drugs. Negatively charged compositions could interact with pattern recognition receptors. The disclosure provides treatments for wound healing, including scar reduction, tissue engineering, bone regeneration, neuronal regeneration, and vascular grafts. Silk promotes collagen production in 2 ways: pro-collagen1A1 secretion and total collagen deposition in human dermal fibroblast 2D cell culture, silk's ability to enhance collagen production can be harnessed for therapeutic benefits in various medical applications. Skin Regeneration: Silk-based dressings or scaffolds can be applied to wounds or burns to promote collagen synthesis. This aids in skin regeneration and accelerates the healing process. Anti-Aging Treatments: Silk-infused cosmetic products can stimulate collagen production, helping to improve skin elasticity and reduce the appearance of wrinkles. Tissue Engineering: Silk scaffolds can be engineered to mimic the extracellular matrix and promote collagen production. This is valuable in creating tissues such as skin, cartilage, and blood vessels for transplantation or repair. Scar Reduction: Silk-based formulations can be used to mitigate scar formation by promoting organized collagen deposition during wound healing. Dermal Fillers: Silk-based materials can be used as dermal fillers to enhance collagen production, restoring volume and improving skin texture. Bone Regeneration: In orthopedic applications, silk scaffolds can stimulate collagen production to aid in bone regeneration and repair. Neuronal regeneration / Repair: Silk conduits can facilitate nerve regeneration by encouraging collagen formation in the nerve tissue. Vascular Grafts: Silk grafts for blood vessels can promote collagen synthesis, improving graft integration and long-term functionality. The disclosure provides for targeted drug delivery. The self-assembly property of silk peptides offers an exciting opportunity for targeted drug delivery. By utilizing this unique characteristic, silk peptides can be engineered to form nanostructures or micelles that encapsulate drugs. These silk-based drug delivery systems can then be designed to target specific tissues or cells, improving the precision and efficacy of drug delivery while reducing off-target effects. The self-assembly property of silk peptides opens up new possibilities in the field of nanomedicine, providing a promising avenue for more efficient and targeted therapeutic interventions. The disclosure provides a combinatorial approach with vitamins having potential synergistic and / or multifactoril effects. The disclosure provides a combinatorial approach with polyphenols, Carotenoids, and fatty acids having potential synergistic and / or multifactoril effects. The disclosure provides a combinatorial approach with cytokines, utilizing novel and repurposed drugs, having potential synergistic and / or multifactoril effects. The disclosure provides a combinatorial approach with minerals sunscreen. UV Protection and Skin Healing: The combination of Silk Fibroin with minerals like Ca and Mg can provide a multifaceted approach to UV protection and skin healing. Silk fibroin's skin healing properties, along with the synergistic effects of UV protection effect of minerals, can contribute to shielding the skin from harmful UV rays and promoting faster healing of UV-induced damage, offering effective skin care benefits. The disclosure provides modes of use / delivery including: sprays, injectable formulations, edible products, nanoparticles or micelles, dressings and bandages, tablets or capsules (regular or utilizing site-specific gastric delivery). Topical creams and gels: Medical use for skin conditions and wound healing. Sprays: Medical use for delivering therapeutics to respiratory or gastrointestinal tissues. Injectable formulations: Medical use for IV, IP, or IM administration to target various tissues. Edible products: Medical use of silk in beverages or oral medications for controlled drug delivery. Nanoparticles or micelles: Medical use for IV, IM, or oral targeted drug delivery. Dressings and bandages: Medical use for wound healing and tissue repair. Implants and scaffolds: Medical use to support tissue regeneration in the body. Tablets or capsules regular or utilizing site-specific gastric delivery: the initial part of the capsule releases for silk amino acid delivery, while the second part releases later for silk peptide delivery, enhancing gut barrier functions. The disclosure provides CLDN1 induction by silk for skin barrier function. Silk has an effect on CLDN1 Induction. Experimental work identified that Silk proteins, induce CLDN1 expression in context of the human skin biopsies and keratinocytes. Data suggests that silk treatment strengthens tight junctions and can improve barrier function. Claudin-1 (CLDN1) Significance: Claudin-1 is a vital transmembrane protein in tight junctions, contributing to the formation and integrity of the skin's barrier function. It helps to regulate the selective permeability of the epidermal barrier. Tight Junction Regulation: CLDN1 plays a pivotal role in the regulation of tight junctions. Upregulating its expression via silk-based interventions could enhance the sealing of the intercellular spaces in the epidermis, limiting water loss and preventing the entry of harmful substances. Barrier Enhancement: By promoting CLDN1 expression, silk-based treatments may enhance the skin's ability to retain moisture, prevent irritants from entering, and safeguard against environmental stressors, effectively fortifying the skin barrier. Clinical Applications: The induction of CLDN1 by silk-based compounds could find application in addressing skin conditions characterized by compromised barrier function, such as atopic dermatitis or aged skin prone to dryness and sensitivity, post-procedure recovery, pediatric dermatology. Infant and pediatric skin is particularly susceptible to barrier disruption, resulting in conditions like infantile eczema, occupational dermatitis conditions, chronic skin conditions like psoriasis and rosacea, cosmetic. The disclosure provides INV induction by silk for skin barrier function. The disclosure provides an amino acid composition of silk that offers the potential to influence baseline amino acid levels when ingested orally. Certain amino acids found in silk have been demonstrated to possess therapeutic benefits. For example, Amino acid content of the silk can include one or more of the following: Alanine: ~42%, Glycine: ~27%, Serine: ~12%, Tyrosine: ~6%, Valine: ~5%, Aspartic acid ~4%, Threonine ~2%, Glutamic acid ~1.5%. Many of these amino acids have beneficial properties to the human body in health and disease. When silk is injected in any form it can contribute also to amino acid compassion in the plasma and promote additional benefits. Below are potentially benefited for specific amino acid. Serine therapeutic benefits include: Neurotransmitter production, Cell membrane structure, Immune system support. Serine: ~12%, is one most abundant amino acids in the silk and if taken orally could be inducing the following benefits: (1) Neurotransmitter production: Serine is a precursor for the synthesis of various neurotransmitters in the brain, including dopamine, norepinephrine, and serotonin. These neurotransmitters are essential for mood regulation, cognitive function, and emotional well-being. (2) Cell membrane structure: Serine is a component of phospholipids, which are essential for building cell membranes. These membranes play a critical role in maintaining cell structure and function. (3) Immune system support: Serine is involved in the production of antibodies and immune system regulation, which helps the body defend against infections and diseases. Glycine therapeutic benefits include: neurotransmitter / neurotransmission, collagen formation, detoxification, energy production, anti-inflammatory effects, bile acid synthesis / lipid metabolism. Glycine: ~27% is one most abundant amino acids in the silk and if taken orally could be inducing the following benefits: (1) Neurotransmitter / neurotransmission. Glycine functions as a neurotransmitter in the central nervous system, where it helps to regulate the excitability of neurons. It is an inhibitory neurotransmitter, which means it has a calming effect on the brain and can promote relaxation and sleep. (2) Collagen formation: Glycine is a significant component of collagen, the most abundant protein in the human body. Collagen provides structural support to connective tissues, skin, bones, and joints. (3) Detoxification: Glycine is involved in the synthesis of glutathione, a powerful antioxidant that helps the body detoxify harmful substances and protect against oxidative stress. (4) Energy production: Glycine plays a role in the synthesis of creatine, a compound important for providing energy to muscles during high-intensity activities. Bile Acid Synthesis / lipid metabolism anti-inflammatory effects: Tyrosine therapeutic benefits include: dopamine production, thyroid hormone synthesis, stress management, skin and pigment formation. Tyrosine: ~6% is in the silk and if taken orally could be inducing the following benefits: (1) Dopamine production: Tyrosine is a precursor to dopamine, a neurotransmitter that plays a vital role in mood regulation, motivation, and focus. Adequate levels of tyrosine can support healthy brain function and mental well-being. (2) Thyroid hormone synthesis: Tyrosine is a component of thyroid hormones (thyroxine and triiodothyronine), which are essential for regulating metabolism, energy production, and overall growth and development. (3) Stress management: Tyrosine can help support the body during periods of stress by aiding in the production of stress hormones like epinephrine and norepinephrine. (4) Skin and pigment formation: Tyrosine is involved in the production of melanin, the pigment responsible for the color of our hair, skin, and eyes. Silk Fibroin can be used in an edible coating for perishable food preservation. The disclosure provides Silk-derived protein products exhibiting antidiabetic, antineoplastic, cardioprotective, neuroprotective, anti-hypercholesterolemic, wound healing, metabolic modulatory, and antioxidant properties. It can also improve memory and learning: The disclosure provides Silk protein, when consumed, may have a dual action: The Silk protein of the disclosure can positively impact gut integrity, reducing inflammation and enhancing nutrient absorption. The Silk protein of the disclosure contributes to the body's amino acid pool, supporting various physiological processes like protein synthesis, tissue repair, detoxification and immune function. The disclosure provides for treatment of: Irritable Bowel Syndrome (IBS), Inflammatory Bowel Disease ulcerative colitis ( UC) , Inflammatory Bowel Disease crohn's disease (CD). The disclosure provides for improving gut barrier, inflammation, gut microbiome, immune dysfunction. The disclosure provides for treatment of Autism, depression, anxiety disorders, Parkinson's Disease, Alzheimer's Disease, multiple sclerosis, traumatic brain injury (TBI). The disclosure provides for improving neuronal regeneration. Silk fibroin enhances peripheral nerve regeneration by improving vascularization within nerve conduits. Valine: ~5%, is one most abundant amino asides in the silk and if taken orally can induce the following benefits: (1) Muscle Health: Valine activates the mTOR pathway, aiding muscle protein synthesis for repair and growth, crucial post-exercise and for healing injuries. (2) Energy Source: Valine contributes to gluconeogenesis, offering an alternate energy source during intense activity or fasting. (3) Immune Support: Valine's potential impact on the mTOR pathway can enhance immune cell production, strengthening immune defenses. (4) Wound Healing: Valine's mTOR activation can accelerate tissue regeneration, expediting wound healing. (5) Neuromuscular Coordination: Valine's role, potentially involving the mTOR pathway, benefits neuromuscular coordination, improving physical performance. The disclosure provides AS77-AS81 silk / unnatural peptides compositions for targeted drug delivery and therapeutic treatments. Low Skid silk (27P) was fractionated by anion exchange chromatography, and the charged eluate was further fractionated by size-exclusion chromatography. Fractions were characterized by SDS- PAGE, analytical size-exclusion chromatography, dynamic light scattering (DLS), and self-assembly assays. The disclosure provides AS90-AS100 silk / unnatural peptides compositions for targeted drug delivery and therapeutic treatments. Low Skid silk (27P) was fractionated by anion exchange chromatography, and the charged eluate was further fractionated by hydrophobic interactions chromatography, and both flowthrough and eluate were further fractionated by size-exclusion chromatography. Fractions were characterized by SDS-PAGE, analytical size-exclusion chromatography, dynamic light scattering (DLS), and self-assembly assays. The disclosure provides AS106-AS111 silk / unnatural peptides compositions for targeted drug delivery and therapeutic treatments. Mid Skid silk (33B) was fractionated by size-exclusion chromatography and fractions were characterized by SDS-PAGE, analytical size-exclusion chromatography, dynamic light scattering (DLS), and self-assembly assays. The disclosure provides AS101-AS105 silk / unnatural peptides compositions for targeted drug delivery and therapeutic treatments. Mid Skid silk (33B) was fractionated by anion exchange chromatography, and the charged eluate was further fractionated by size-exclusion chromatography. Fractions were characterized by SDS- PAGE, analytical size-exclusion chromatography, dynamic light scattering (DLS), and self-assembly assays. The disclosure provides Mid Skid (33B) for targeted drug delivery, and therapeutic treatments. The disclosure provides: Self-polymerizing bioactive extracellular matrix for wound healing and tissue repair, self-polymerizing silk polypeptide formulation as ligand- receptor avidity amplifier, self-polymerizing silk polypeptide formulation as receptor turnover-blocking ligand scaffold to prolong cell signaling time, self-polymerizing silk polypeptide-antibody conjugates for combinatorial targeting of tumor associated antigens to drive physical association of tumor cells with CD8+ T cells, self- polymerizing silk polypeptide solution as biosynthetic pulmonary surfactant to maintain pulmonary compliance while restoring alevolar epithelial integrity by self- assembly in acute respiratory distress syndrome. The disclosure provides for treatment of inflammatory conditions effecting macrophage polarization for treating inflammatory diseases. Silk suppresses the production of inflammatory cytokines (IL-6, TNF-alpha) in macrophage cell lines treated with LPS, while simultaneously promoting the release of the anti- inflammatory cytokine IL-10. The disclosure provides a composition comprising a plurality of peptides or protein fragments of fibroin heavy chain, fibroin light chain, and / or fibrohexamerin (p25), the composition comprising one or more fractions, wherein the plurality of peptides or protein fragments comprises a fibroin peptide or protein fragment comprising an amino acid modification, substitution, or replacement. In some embodiments, the plurality of peptides or protein fragments having a weight average molecular weight (Mw) selected from between about 1 kDa and about 20 kDa, from between about 20 kDa and about 40 kDa, from between about 40 kDa and about 60 kDa, from between about 60 kDa and about 80 kDa, from between about 80 kDa and about 100 kDa, from between about 100 kDa and about 120 kDa, from between about 120 kDa and about 140 kDa, or from between about 140 kDa and about 160 kDa, from between about 160 kDa and about 180 kDa, from between about 180 kDa and about 200 kDa, or from between about 200 kDa and about 250 kDa, and a polydispersity between 1 and about 1.7, between 1 and less than 3, or between 1 and less than 5. In some embodiments, the plurality of peptides or protein fragments in a fraction having a weight average molecular weight (Mw) selected from between about 10 kDa and about 20 kDa, from between about 20 kDa and about 40 kDa, from between about 40 kDa and about 60 kDa, from between about 60 kDa and about 80 kDa, from between about 80 kDa and about 100 kDa, from between about 100 kDa and about 120 kDa, from between about 120 kDa and about 140 kDa, from between about 140 kDa and about 160 kDa, or from between about 160 kDa and about 180 kDa, and a polydispersity between 1 and about 1.1, or 1 and about 1.2, or between 1 and less than 3, or between 1 and less than 5. In some embodiments, the plurality of peptides or protein fragments in a fraction having a weight average molecular weight (Mw) selected from between about 10 kDa and about 20 kDa, from between about 20 kDa and about 40 kDa, from between about 40 kDa and about 60 kDa, from between about 60 kDa and about 80 kDa, from between about 80 kDa and about 100 kDa, from between about 100 kDa and about 120 kDa, or from between about 120 kDa and about 140 kDa, and a polydispersity between 1 and about 1.1, or 1 and about 1.2, or between 1 and less than 3, or between 1 and less than 5. In some embodiments, the plurality of peptides or protein fragments in a fraction having a weight average molecular weight (Mw) selected from between about 60 kDa and about 80 kDa, from between about 80 kDa and about 100 kDa, or from between about 100 kDa and about 120 kDa, and a polydispersity between 1 and about 1.1, or between 1 and less than 3, or between 1 and less than 5. In some embodiments, the plurality of peptides or protein fragments in a fraction having a weight average molecular weight (Mw) selected from between about 10 kDa and about 20 kDa, from between about 20 kDa and about 40 kDa, from between about 40 kDa and about 60 kDa, from between about 60 kDa and about 80 kDa, from between about 80 kDa and about 100 kDa, or from between about 100 kDa and about 110 kDa, and a polydispersity between 1 and about 1.1, or 1 and about 1.2, or between 1 and less than 3, or between 1 and less than 5. In some embodiments, the plurality of peptides or protein fragments in a fraction having a weight average molecular weight (Mw) selected from between about 60 kDa and about 80 kDa, from between about 80 kDa and about 100 kDa, from between about 100 kDa and about 120 kDa, or from between about 120 kDa and about 140 kDa, and a polydispersity between 1 and about 1.1, or between 1 and less than 3, or between 1 and less than 5. In some embodiments, the plurality of peptides or protein fragments in a fraction having a weight average molecular weight (Mw) selected from between about 20 kDa and about 40 kDa, or from between about 40 kDa and about 60 kDa, and a polydispersity between 1 and about 1.1, or 1 and about 1.2, or between 1 and less than 3, or between 1 and less than 5. In some embodiments, the one or more fractions are selected from AS77, AS78, AS79, AS80, and AS81. In some embodiments, the one or more fractions are selected from AS82, AS83, AS84, AS85, AS86, AS87, AS88, and AS89. In some embodiments, the one or more fractions are selected from AS90, AS91, AS92, AS93, and AS94. In some embodiments, the one or more fractions are selected from AS95, AS96, AS97, AS98, AS99, and AS100. In some embodiments, the plurality of peptides or protein fragments having a weight average molecular weight (Mw) selected from between about 40 kDa and about 60 kDa, from between about 60 kDa and about 80 kDa, from between about 80 kDa and about 100 kDa, from between about 100 kDa and about 120 kDa, from between about 120 kDa and about 140 kDa, from between about 140 kDa and about 160 kDa, from between about 160 kDa and about 180 kDa, from between about 180 kDa and about 200 kDa, or from between about 200 kDa and about 220 kDa, and a polydispersity between 1 and about 1.7, or between 1 and less than 3, or between 1 and less than 5. In some embodiments, the plurality of peptides or protein fragments in a fraction having a weight average molecular weight (Mw) selected from between about 40 kDa and about 60 kDa, from between about 60 kDa and about 80 kDa, from between about 80 kDa and about 100 kDa, from between about 100 kDa and about 120 kDa, from between about 120 kDa and about 140 kDa, from between about 140 kDa and about 160 kDa, from between about 160 kDa and about 180 kDa, from between about 180 kDa and about 200 kDa, or from between about 200 kDa and about 210 kDa, and a polydispersity between 1 and about 1.2, or 1 and about 1.3, or between 1 and less than 3, or between 1 and less than 5. In some embodiments, the plurality of peptides or protein fragments in a fraction having a weight average molecular weight (Mw) selected from between about 40 kDa and about 60 kDa, from between about 60 kDa and about 80 kDa, from between about 80 kDa and about 100 kDa, or from between about 100 kDa and about 110 kDa, and a polydispersity between 1 and about 1.1, or 1 and about 1.2, or between 1 and less than 3, or between 1 and less than 5. In some embodiments, the plurality of peptides or protein fragments in a fraction having a weight average molecular weight (Mw) selected from between about 60 kDa and about 80 kDa, from between about 80 kDa and about 100 kDa, from between about 100 kDa and about 120 kDa, from between about 120 kDa and about 140 kDa, from between about 140 kDa and about 160 kDa, from between about 160 kDa and about 180 kDa, from between about 180 kDa and about 200 kDa, or from between about 200 kDa and about 210 kDa, and a polydispersity between 1 and about 1.2, or 1 and about 1.3, or between 1 and less than 3, or between 1 and less than 5. In some embodiments, the one or more fractions are selected from AS101, AS102, AS103, AS104, and AS105. In some embodiments, the one or more fractions are selected from AS106, AS107, AS108, AS109, AS110, and AS111. In some embodiments, an amino acid is selected from M, R, V, K, T, F, I, L, C, A, Q, Y, N, D, E, G, S, H, P, and W. In some embodiments, a peptide or protein fragment comprises between about 2 and about 100 amino acids. In some embodiments, the peptide or protein fragment comprises between about 2 and about 25 amino acids. In some embodiments, the peptide or protein fragment comprises between about 25 and about 50 amino acids. In some embodiments, the peptide or protein fragment comprises between about 50 and about 75 amino acids. In some embodiments, the peptide or protein fragment comprises between about 75 and about 100 amino acids. In some embodiments, the peptide or protein fragment comprises between about 100 and about 125 amino acids. In some embodiments, the peptide or protein fragment comprises between about 125 and about 150 amino acids. In some embodiments, the peptide or protein fragment comprises between about 150 and about 200 amino acids. In some embodiments, the peptide or protein fragment comprises between about 200 and about 250, 300, 350, 400, 450, or 500 amino acids. In some embodiments, a peptide or protein fragment comprises between one and five modifications, substitutions, and / or replacements. In some embodiments, the peptide or protein fragment comprises one modification, substitution, and / or replacement. In some embodiments, the peptide or protein fragment comprises two modifications, substitutions, and / or replacements. In some embodiments, the peptide or protein fragment comprises three modifications, substitutions, and / or replacements. In some embodiments, the peptide or protein fragment comprises four modifications, substitutions, and / or replacements. In some embodiments, the peptide or protein fragment comprises five modifications, substitutions, and / or replacements. In some embodiments, the peptide or protein fragment comprises six modifications, substitutions, and / or replacements. In some embodiments, the peptide or protein fragment comprises seven modifications, substitutions, and / or replacements. In some embodiments, the peptide or protein fragment comprises eight modifications, substitutions, and / or replacements. In some embodiments, the peptide or protein fragment comprises nine modifications, substitutions, and / or replacements. In some embodiments, the peptide or protein fragment comprises ten modifications, substitutions, and / or replacements. In some embodiments, the fibroin is a fibroin heavy chain, and wherein a modification, substitution, and / or replacement is at a position corresponding to any one position from 1 to 5263 of the fibroin heavy chain. In some embodiments, the fibroin is a fibroin light chain, and wherein a modification, substitution, and / or replacement is at a position corresponding to any one position from 1 to 262 of the fibroin light chain. In some embodiments, the fibroin is a fibrohexamerin (p25) chain, and wherein a modification, substitution, and / or replacement is at a position corresponding to any one position from 1 to 220 of the fibrohexamerin (p25) chain. In some embodiments, a modification, substitution, and / or replacement is selected from an asparagine to aspartic acid modification, substitution, and / or replacement, a glutamine to glutamic acid modification, substitution, and / or replacement, and a methionine to methionine oxide modification, substitution, and / or replacement. In some embodiments, a modification, substitution, and / or replacement is at fibroin heavy chain position selected from Q58, M64, N68, N70, N77, M80, N93, M103, Q125, N132, Q139, Q275, N4191, Q5216, and / or N5262. In some embodiments, a modification, substitution, and / or replacement is at fibroin light chain position selected from N23, Q24, N28, M69, N105, N108, N118, N136, N138, Q149, N186, N200, Q202, N204, N240, N248, and / or Q255. In some embodiments, a modification, substitution, and / or replacement is at fibrohexamerin (p25) position selected from Q62, N93, M120, N149, N172, N174, and / or N202. In some embodiments, each modification, substitution, and / or replacement is independently ranging in the composition between about 1% to about 99%. In some embodiments, each modification, substitution, and / or replacement is independently ranging in the composition between about 1% to about 10%. In some embodiments, each modification, substitution, and / or replacement is independently ranging in the composition between about 10% to about 20%. In some embodiments, each modification, substitution, and / or replacement is independently ranging in the composition between about 20% to about 30%. In some embodiments, each modification, substitution, and / or replacement is independently ranging in the composition between about 30% to about 40%. In some embodiments, each modification, substitution, and / or replacement is independently ranging in the composition between about 40% to about 50%. In some embodiments, each modification, substitution, and / or replacement is independently ranging in the composition between about 50% to about 60%. In some embodiments, each modification, substitution, and / or replacement is independently ranging in the composition between about 60% to about 70%. In some embodiments, each modification, substitution, and / or replacement is independently ranging in the composition between about 70% to about 80%. In some embodiments, each modification, substitution, and / or replacement is independently ranging in the composition between about 80% to about 90%. In some embodiments, each modification, substitution, and / or replacement is independently ranging in the composition between or about 90% to about 99%. As used herein, a % modification, substitution, and / or replacement is defined as (number of peptide or protein fragments comprising a modification, substitution, and / or replacement at a specific position, divided by the total number of peptide or protein fragments which include the specific position, whether comprising a modification, substitution, and / or replacement, or not) x 100. In some embodiments, a molecular weight is determined by MALS. In some embodiments, the composition comprises a population of neutral fibroin fragments. In some embodiments, the composition comprises a population of positively charged fibroin fragments. In some embodiments, the composition comprises a population of negatively charged fibroin fragments. In some embodiments, the fibroin fragments have a weight average molecular weight from about 1 kDa to about 250 kDa. In some embodiments, the composition comprises a fibroin fragment subpopulation having a weight average molecular weight selected from between about 5 kDa to about 10 kDa, between about 10 kDa to about 40 kDa, between about 40 kDa to about 70 kDa, between about 70 kDa to about 100 kDa, between about 100 kDa to about 130 kDa, between about 130 kDa to about 150 kDa, between about 150 kDa to about 180 kDa, between about 180 kDa to about 210 kDa, or between about 210 kDa to about 240 kDa. In some embodiments, the composition comprises a fibroin fragment subpopulation having a weight average molecular weight selected from between about 20 kDa to about 50 kDa, between about 50 kDa to about 80 kDa, between about 80 kDa to about 110 kDa, between about 110 kDa to about 140 kDa, between about 140 kDa to about 170 kDa, between about 170 kDa to about 200 kDa, between about 200 kDa to about 230 kDa, or between about 230 kDa to about 250 kDa. In some embodiments, the composition comprises a fibroin fragment subpopulation each having a polydispersity selected from between 1 to about 3. In some embodiments, the composition comprises a fibroin fragment subpopulation having an isoelectric point selected from between about 4.4 to about 9.6. In some embodiments, the composition comprises a fibroin fragment subpopulation having a self assembly rate factor selected from between 0 to about 5. In some embodiments, the composition comprises a fibroin fragment subpopulation having a self assembly rate factor selected from between about 0.6 to about 4. In some embodiments, the composition comprises a fibroin fragment subpopulation having a self assembly factor selected from between about 0.5 to about 0.9. In some embodiments, the composition comprises a fibroin fragment subpopulation having a self assembly rate factor selected from between about 5 to about 11. In some embodiments, the composition comprises a fibroin fragment subpopulation having an Amax selected from between 0 to about 0.7. In some embodiments, the composition comprises a fibroin fragment subpopulation having an Amaxselected from between about 0.5 to about 0.8. In some embodiments, the composition comprises a fibroin fragment subpopulation having a t0.5(min) selected from between 0 to about 1500. In some embodiments, the composition comprises a fibroin fragment subpopulation having a t0.5(min) selected from between 0 to about 1000. In some embodiments, the fibroin fragments comprise one or more amino acid residue modifications selected from an asparagine to aspartic acid modification, a glutamine to glutamic acid modification, and a methionine to methionine oxide modification. In some embodiments, a plurality of modified fibroin fragments comprise one modification. In some embodiments, a plurality of modified fibroin fragments comprise two modifications. In some embodiments, a plurality of modified fibroin fragments comprise three modifications. In some embodiments, the composition comprises one or more fibroin fragments having an asparagine residue replaced by an aspartic acid residue, wherein the degree of replacement within the composition is selected from between about 1% to 100%. In some embodiments, the composition comprises one or more fibroin fragments having an asparagine residue replaced by an aspartic acid residue, wherein the fraction of fibroin fragments within the total population of fibroin fragments in the composition is selected from between about 1% to 100%, by either number or weight. In some embodiments, the asparagine to aspartic acid modification is at one or more positions selected from N23, N28, N108, N118, N136, N186, N200, N204, N240, N248, N68, N70, N77, N5262, N93, N132, N149, N172, N174, N202, N105, N4191. In some embodiments, the composition comprises one or more fibroin fragments having a glutamine residue replaced by a glutamic acid residue, wherein the degree of replacement within the composition is selected from between about 1% to 100%. In some embodiments, the composition comprises one or more fibroin fragments having a glutamine residue replaced by a glutamic acid residue, wherein the fraction of fibroin fragments within the total population of fibroin fragments in the composition is selected from between about 1% to 100%, by either number or weight. In some embodiments, the glutamine to glutamic acid modification is at one or more positions selected from Q24, Q149, Q202, Q58, Q139, Q275, Q5216, Q255, and Q125. In some embodiments, the composition comprises one or more fibroin fragments having a methionine residue replaced by a methionine sulfoxide residue, wherein the degree of replacement within the composition is selected from between about 1% to 100%. In some embodiments, the composition comprises one or more fibroin fragments having a methionine residue replaced by a methionine sulfoxide residue, wherein the fraction of fibroin fragments within the total population of fibroin fragments in the composition is selected from between about 1% to 100%, by either number or weight. In some embodiments, the methionine to methionine oxide modification is at the M64 position. In some embodiments, a % modification is defined as (number of modified fibroin fragments having a modification at a specific position divided by the total number of fibroin fragments which includes the specific position, modified or unmodified) x 100. In some embodiments, each modification is independently ranging in the composition between about 1% to about 99%. In some embodiments, the silk fibroin fragment comprises a sequence at least 70% identical to DASGAVIEEQITTK. In some embodiments, the silk fibroin fragment comprises a sequence at least 70% identical to VADGGYSGYEY. In some embodiments, the silk fibroin fragment comprises a sequence at least 70% identical to GAGYGVGAGAGY. In some embodiments, the silk fibroin fragment comprises a sequence at least 70% identical to YAWSSKSDFE. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutically acceptable carrier comprises or is formulated as one or more of a cosmeceutical, a suspension, an emulsion, a powder, a solution, a dispersion, or an elixir. In some embodiments, the pharmaceutically acceptable carrier comprises or is formulated as one or more of a gel, a jelly, a cream, a lotion, a foam, a slurry, an ointment, an oil, a paste, a suppository, a spray, a semisolid composition, a solid composition, a stick, or a mousse. In some embodiments, the pharmaceutically acceptable carrier comprises one or more of aliphatic oil, a fatty alcohol, a fatty acid, a glyceride, an acylglycerol, and a phospholipid. In some embodiments, the pharmaceutically acceptable carrier comprises one or more of a monoglyceride, a diglyceride, or a triglyceride. In some embodiments, the pharmaceutically acceptable carrier comprises an aqueous phase. In some embodiments, the pharmaceutically acceptable carrier comprises an oil-in-water emulsion or a water-in-oil emulsion. In some embodiments, the pharmaceutically acceptable carrier comprises one or more of a hydrocarbon oil, a fatty acid, a fatty oil, a fatty acid ester, or a cationic quaternary ammonium salt. In some embodiments, the composition remains on the skin after rinsing. The disclosure provides a dual syringe kit comprising a first syringe including the composition of any one of the embodiments disclosed herein comprising fibroin fragments; and a second syringe including a silk-hyaluronic acid hydrogel. In some embodiments, the first syringe comprises about 0.1 mL, about 0.2 mL, about 0.3 mL, about 0.4 mL, or about 0.5 mL of the composition. In some embodiments, the firoin fragments are formulated in an aqueous solution. In some embodiments, the firoin fragments are formulated in a gel composition. In some embodiments, the second syringe comprises about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, about 1.0 mL, about 1.2 mL, about 1.3 mL, about 1.4 mL, or about 6.5 mL of the silk-hyaluronic acid hydrogel. In some embodiments, the silk-hyaluronic acid hydrogel is crosslinked. In some embodiments, the composition and the silk- hyaluronic acid hydrogel are mixed together to form an admixture before being applied to a skin of the subject. In some embodiments, the admixture is applied to the skin of the subject using a derma roller. In some embodiments, the admixture is applied to the skin of the subject using a microchanneling technique. In some embodiments, the admixture is applied to the skin of the subject using fractional microneedle radiofrequency (RF). In some embodiments, the admixture is applied to the subject using platelet-rich plasma (PRP) therapy. The disclosure provides a method of treatment or prevention of a disorder, disease, or condition in a subject in need thereof, the method comprising administering to the subject the admixture of any one of the embodiments disclosed herein. In some embodiments, the admixture comprising the composition of any one of the embodiments disclosed herein is administered to the subject. In some embodiments, the composition of any one of the embodiments disclosed herein in the admixture of any one of the embodiments disclosed herein is administered to the subject. In some embodiments, the subject in need experiences increased stimulation of collagen production post-administration. In some embodiments, the subject in need experiences improved skin hydration post- administration. In some embodiments, the subject in need experiences improved skin texture and elasticity post-administration. In some embodiments, the subject in need experiences a reduction in skin redness post-administration. In some embodiments, the subject in need experiences a reduction in inflammation post-administration. The disclosure provides a method for identifying a protein, comprising employing Far Western Blot, SDS-polyacrylamide gel electrophoresis (SDS-PAGE), and / or LC / MS analysis, wherein the fibroin fragment of any one of the embodiments disclosed herein binds to the protein. In some embodiments, the fibroin fragment is a polypeptide composition derived from B. mori silk. In some embodiments, the protein is in a human tissue. In some embodiments, the human tissue is skin. In some embodiments, the protein in the human tissue is Keratin Type II Cytoskeletal 1 (KRT1), or Keratin type I cytoskeletal 10 (KRT10). In some embodiments, compositions of the present disclosure include peptides compositions selected from compositions #1001 to #2450, having weight average molecular weights selected from about 1 kDa to about 145 kDa, and a polydispersity selected from between 1 and about 5 (including, without limitation, a polydispersity of 1), between 1 and about 1.5 (including, without limitation, a polydispersity of 1), between about 1.5 and about 2, between about 1.5 and about 3, between about 2 and about 2.5, between about 2.5 and about 3, between about 3 and about 3.5, between about 3.5 and about 4, between about 4 and about 4.5, and between about 4.5 and about 5: PDI ( b t) -5 0 0 0 0 kDa 1041 1042 1043 1044 1045 1046 1047 1048 1049 1050 kDa 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 70 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 kDa 1501 1502 1503 1504 1505 1506 1507 1508 1509 1510 kDa 1511 1512 1513 1514 1515 1516 1517 1518 1519 1520 30 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 kDa 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 kDa 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 90 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 143 kDa 2421 2422 2423 2424 2425 2426 2427 2428 2429 2430 144 kDa 2431 2432 2433 2434 2435 2436 2437 2438 2439 2440 50 applications in various fields are known and are described for example in applications WO2019 / 005848, WO2020132331, WO2021 / 258030, and WO2024 / 059862, as well as U.S. Patents Nos.9,187,538, 9,511,012, 9,517,191, 9,522,107, 9,522,108, 9,545,369, and 10,166,177, 10,287,728 and 10,301,768, all of which are incorporated herein in their entireties. Raw silk from silkworm Bombyx mori is composed of two primary proteins: silk fibroin (approximately 75%) and sericin (approximately 25%). Silk fibroin is a fibrous protein with a semi-crystalline structure that provides stiffness and strength. As used herein, the term “silk fibroin” means the fibers of the cocoon of Bombyx mori having a weight average molecular weight of about 370,000 Da. The crude silkworm fiber consists of a double thread of fibroin. The adhesive substance holding these double fibers together is sericin. The silk fibroin is composed of a heavy chain having a weight average molecular weight of about 350,000 Da (H chain), and a light chain having a weight average molecular weight about 25,000 Da (L chain). Silk fibroin is an amphiphilic polymer with large hydrophobic domains occupying the major component of the polymer, which has a high molecular weight. The hydrophobic regions are interrupted by small hydrophilic spacers, and the N- and C- termini of the chains are also highly hydrophilic. The hydrophobic domains of the H- chain contain a repetitive hexapeptide sequence of Gly-Ala-Gly-Ala-Gly-Ser and repeats of Gly-Ala / Ser / Tyr dipeptides, which can form stable anti-parallel-sheet crystallites. The amino acid sequence of the L-chain is non-repetitive, so the L-chain is more hydrophilic and relatively elastic. The hydrophilic (Tyr, Ser) and hydrophobic (Gly, Ala) chain segments in silk fibroin molecules are arranged alternatively such that allows self-assembling of silk fibroin molecules. Definitions As used in the preceding sections and throughout the rest of this specification, unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one skilled in the art to which this disclosure belongs. All patents and publications referred to herein are incorporated by reference in their entireties. All percentages, parts and ratios are based upon the total weight of the eye care compositions of the present disclosure, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the active level and, therefore, do not include solvents or by-products that may be included in commercially available materials, unless otherwise specified. The term “weight percent” may be denoted as “wt. %” or % w / w herein. As used herein, the term “a”, “an”, or “the” generally is construed to cover both the singular and the plural forms. The term “about” as used herein, generally refers to a particular numeric value that is within an acceptable error range as determined by one of ordinary skill in the art, which will depend in part on how the numeric value is measured or determined, i.e., the limitations of the measurement system. For example, “about” can mean zero variation, and a range of ±20%, ±10%, or ±5% of a given numeric value. As used herein, the term “dermatologically acceptable carrier” means a carrier suitable for use in contact with mammalian keratinous tissue without causing any adverse effects such as undue toxicity, incompatibility, instability, allergic response, for example. A dermatologically acceptable carrier may include, without limitations, water, liquid or solid emollients, humectants, solvents, and the like. As used herein, the term “hydrophilic-lipophilic balance” (HLB) of a surfactant and / or emulsifier is a measure of the degree to which it is hydrophilic or hydrophobic, as determined by calculating values for the different regions of the molecule, as described by Griffin’s method HLB = 20 * Mh / M, where Mh is the molecular mass of the hydrophilic portion of the surfactant and / or emulsifier, and M is the molecular mass of the entire surfactant and / or emulsifier molecule, giving a result on a scale of 0 to 20. A HLB value of 0 corresponds to a completely lipophilic molecule, and a value of 20 corresponds to a completely hydrophilic molecule. The HLB value can be used to predict the surfactant and / or emulsifier properties of a molecule: HLB < 10: Lipid- soluble (water-insoluble), HLB >10: Water-soluble (lipid-insoluble), HLB = 1-3: anti- foaming agent, 3-6: W / O (water-in-oil) emulsifier, 7-9: wetting and spreading agent, 8-16: O / W (oil-in-water) emulsifier, 13-16: detergent, 16-18: solubilizer or hydrotrope. As used herein, “average weight average molecular weight” refers to an average of two or more values of weight average molecular weight of silk fibroin or fragments thereof of the same compositions, the two or more values determined by two or more separate experimental readings. As used herein, the term polymer “polydispersity (PD)” is generally used as a measure of the broadness of a molecular weight distribution of a polymer, and is defined by the formula polydispersity PD =ெ௪ெ^. As used herein, the term “substantially may refer to silk fibroin- based protein fragments that are distributed in a distribution about an identified molecular weight. As used herein, the term “substantially homogeneous” may refer to an even distribution of a component or an additive, for example, silk fibroin fragments, dermatologically acceptable carrier, etc., throughout a composition of the present disclosure. As used herein, the terms “silk fibroin peptide,” “silk fibroin protein fragment,” and “silk fibroin fragment” are used interchangeably. Molecular weight or number of amino acids units are defined when molecular size becomes an important parameter. As used herein, the term “fast-dissolving solid forms” refers to fast-dissolving solid forms including freeze dried forms (cakes, wafers, thin films), and compressed tablets. As used herein, the terms “peptide” or “protein” refers to a chain of amino acids that are held together by peptide bonds (also called amide bonds). The basic distinguishing factors for proteins and peptides are size and structure. Peptides are smaller than proteins. Traditionally, peptides are defined as molecules that consist of between 2 and 50 amino acids, whereas proteins are made up of 50 or more amino acids. In addition, peptides tend to be less well defined in structure than proteins, which can adopt complex conformations known as secondary, tertiary, and quaternary structures. As used herein, the term “fibroin” or “silk protein” is a type of structural protein produced by certain spider and insect species that produce silk (See definition provided in WIPO Pearl-WIPO’s Multilingual Terminology Portal database, https: / / wipopearl.wipo.int / en / linguistic). Fibroin may include silkworm fibroin, insect or spider silk protein (e.g., spidroin), recombinant spider protein, silk proteins present in other spider silk types, e.g., tubuliform silk protein (TuSP), flagelliform silk protein, minor ampullate silk proteins, aciniform silk protein, pyriform silk protein, aggregate silk glue), silkworm fibroin produced by genetically modified silkworm, or recombinant silkworm fibroin. As used herein, the term “silk fibroin” refers to silkworm fibroin, silk fibroin produced by genetically modified silkworm, or recombinant silkworm fibroin (See (1) Narayan Ed., Encyclopedia of Biomedical Engineering, Vol.2, Elsevier, 2019; (2) Kobayashi et al. Eds, Encyclopedia of Polymeric Nanomaterials, Springer, 2014, https: / / link.springer.com / referenceworkentry / 10.1007%2F978-3-642-36199-9_323-1). In an embodiment, silk fibroin is obtained from Bombyx mori. The term “solid solution” as used herein, refers to the active agent molecularly dissolved in the solid excipient matrix such as hydrophobic polymers, wherein the active agent is miscible with the polymer matrix excipient. The term “solid dispersion” as used herein, refers to the active agent dispersed as crystalline or amorphous particles, wherein the active agent is dispersed in an amorphous polymer and is distributed at random between the polymer matrix excipient. As used herein, the term “substantially homogeneous” may refer to silk fibroin-based protein fragments that are distributed in a normal distribution about an identified molecular weight. As used herein, the term “substantially homogeneous” may also refer to an even distribution of a component or an additive, for example, silk fibroin- based protein fragments, dermatologically acceptable carrier, etc., throughout the silk eye care composition. As used herein, the term “surface tension” refers to the tendency of fluid surfaces to shrink into the minimum surface area possible. At liquid–air interfaces, surface tension results from the greater attraction of liquid molecules to each other (due to cohesion) than to the molecules in the air (due to adhesion). The net effect is an inward force at its surface that causes the liquid to behave as if its surface were covered with a stretched elastic membrane. Because of the relatively high attraction of water molecules to each other through a web of hydrogen bonds, water has a higher surface tension (72.8 mN / m at 20 °C) than most other liquids. SPF Definitions and Properties As used herein, “silk protein fragments” (SPF) include, without limitation, one or more of: “silk fibroin fragments” as defined herein; “recombinant silk fragments” as defined herein; “spider silk fragments” as defined herein; “silk fibroin-like protein fragments” as defined herein; “chemically modified silk fragments” as defined herein; “sericin or sericin fragments” as defined herein; and / or modified silk fragments disclosed herein, e.g., and without limitation, fibroin peptides and / or protein fragments wherein at least one of the amino acids is modified, substituted, or replaced as disclosed herein. SPF may have any molecular weight values or ranges described herein, and any polydispersity values or ranges described herein. SPF Molecular Weight and Polydispersity In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 1 to about 5 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 5 to about 10 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 10 to about 15 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 15 to about 20 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 14 to about 30 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 20 to about 25 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 25 to about 30 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 30 to about 35 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 35 to about 40 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 39 to about 54 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 40 to about 45 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 45 to about 50 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 50 to about 55 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 55 to about 60 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 60 to about 65 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 65 to about 70 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 70 to about 75 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 75 to about 80 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 80 to about 85 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 85 to about 90 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 90 to about 95 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 95 to about 100 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 100 to about 105 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 105 to about 110 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 110 to about 115 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 115 to about 120 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 120 to about 125 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 125 to about 130 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 130 to about 135 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 135 to about 140 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 140 to about 145 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 145 to about 150 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 150 to about 155 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 155 to about 160 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 160 to about 165 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 165 to about 170 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 170 to about 175 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 175 to about 180 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 180 to about 185 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 185 to about 190 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 190 to about 195 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 195 to about 200 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 200 to about 205 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 205 to about 210 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 210 to about 215 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 215 to about 220 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 220 to about 225 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 225 to about 230 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 230 to about 235 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 235 to about 240 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 240 to about 245 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 245 to about 250 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 250 to about 255 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 255 to about 260 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 260 to about 265 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 265 to about 270 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 270 to about 275 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 275 to about 280 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 280 to about 285 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 285 to about 290 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 290 to about 295 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 295 to about 300 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 300 to about 305 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 305 to about 310 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 310 to about 315 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 315 to about 320 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 320 to about 325 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 325 to about 330 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 330 to about 335 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 335 to about 340 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 340 to about 345 kDa. In an embodiment, a composition of the present disclosure includes SPF having an average weight average molecular weight selected from between about 345 to about 350 kDa. As used herein, the term “fibroin” includes silk worm fibroin and insect or spider silk protein. In an embodiment, fibroin is obtained from Bombyx mori. Raw silk from Bombyx mori is composed of two primary proteins: silk fibroin (approximately 75%) and sericin (approximately 25%). As used herein, the term “silk fibroin” means the fibers of the cocoon of Bombyx mori having a weight average molecular weight of about 370,000 Da. Methods of making silk fibroin protein fragments, and / or compositions thereof, are known and are described for example in U.S. Patents Nos.9,187,538, 9,511,012, 9,517,191, 9,522,107, 9,522,108, 9,545,369, and 10,166,177. Recombinant silk described in patents and patent applications, incorporated by reference herein: US 2004590196, US 7,754,851, US 2007654470, US 7,951,908, US 2010785960, US 8,034,897, US 20090263430, US 2008226854, US 20090123967, US 2005712095, US 2007991037, US 20090162896, US 200885266, US 8,372,436, US 2007989907, US 2009267596, US 2010319542, US 2009265344, US 2012684607, US 2004583227, US 8,030,024, US 2006643569, US 7,868,146, US 2007991916, US 8,097,583, US 2006643200, US 8,729,238, US 8,877,903, US 20190062557, US 20160280960, US 20110201783, US 2008991916, US 2011986662, US 2012697729, US 20150328363, US 9,034,816, US 20130172478, US 9,217,017, US 20170202995, US 8,721,991, US 2008227498, US 9,233,067, US 8,288,512, US 2008161364, US 7,148,039, US 1999247806, US 2001861597, US 2004887100, US 9,481,719, US 8,765,688, US 200880705, US 2010809102, US 8,367,803, US 2010664902, US 7,569,660, US 1999138833, US 2000591632, US 20120065126, US 20100278882, US 2008161352, US 20100015070, US 2009513709, US 20090194317, US 2004559286, US 200589551, US 2008187824, US 20050266242, US 20050227322, and US 20044418. Recombinant silk is also described in other patents and patent applications, incorporated by reference herein: US 20190062557, US 20150284565, US 20130225476, US 20130172478, US 20130136779, US 20130109762, US 20120252294, US 20110230911, US 20110201783, US 20100298877, US 10,478,520, US 10,253,213, US 10,072,152, US 9,233,067, US 9,217,017, US 9,034,816, US 8,877,903, US 8,729,238, US 8,721,991, US 8,097,583, US 8,034,897, US 8,030,024, US 7,951,908, US 7,868,146, and US 7,754,851. Recombinant silk protein and / or methods described herein, may include one or more recombinant silk proteins described above or recited in U.S. Patent Nos. 8,173,772, 8,278,416, 8,618,255, 8,642,734, 8,691,581, 8,729,235, 9,115,204, 9,157,070, 9,309,299, 9,644,012, 9,708,376, 9,051,453, 9,617,315, 9,968,682, 9,689,089, 9,732,125, 9,856,308, 9,926,348, 10,065,997, 10,316,069, and 10,329,332; and U.S. Patent Publication Nos.2009 / 0226969, 2011 / 0281273, 2012 / 0041177, 2013 / 0065278, 2013 / 0115698, 2013 / 0316376, 2014 / 0058066, 2014 / 0079674, 2014 / 0245923, 2015 / 0087046, 2015 / 0119554, 2015 / 0141618, 2015 / 0291673, 2015 / 0291674, 2015 / 0239587, 2015 / 0344542, 2015 / 0361144, 2015 / 0374833, 2015 / 0376247, 2016 / 0024464, 2017 / 0066804, 2017 / 0066805, 2015 / 0293076, 2016 / 0222174, 2017 / 0283474, 2017 / 0088675, 2019 / 0135880, 2015 / 0329587, 2019 / 0040109, 2019 / 0135881, 2019 / 0177363, 2019 / 0225646, 2019 / 0233481, 2019 / 0031842, 2018 / 0355120, 2019 / 0186050, 2019 / 0002644, 2020 / 0031887, 2018 / 0273590, 20191 / 094403, 2019 / 0031843, 2018 / 0251501, 2017 / 0066805, 2018 / 0127553, 2019 / 0329526, 2020 / 0031886, 2018 / 0080147, 2019 / 0352349, 2020 / 0043085, 2019 / 0144819, 2019 / 0228449, 2019 / 0340666, 2020 / 0000091, 2019 / 0194710, 2019 / 0151505, 2018 / 0265555, 2019 / 0352330, 2019 / 0248847, and 2019 / 0378191, the entirety of which are incorporated herein by reference. As used herein, the term “substantially free of inorganic residuals” means that the composition exhibits residuals of 0.1 % (w / w) or less. In an embodiment, substantially free of inorganic residuals refers to a composition that exhibits residuals of 0.05% (w / w) or less. In an embodiment, substantially free of inorganic residuals refers to a composition that exhibits residuals of 0.01 % (w / w) or less. In an embodiment, the amount of inorganic residuals is between 0 ppm (“non-detectable” or “ND”) and 1000 ppm. In an embodiment, the amount of inorganic residuals is ND to about 500 ppm. In an embodiment, the amount of inorganic residuals is ND to about 400 ppm. In an embodiment, the amount of inorganic residuals is ND to about 300 ppm. In an embodiment, the amount of inorganic residuals is ND to about 200 ppm. In an embodiment, the amount of inorganic residuals is ND to about 100 ppm. In an embodiment, the amount of inorganic residuals is between 10 ppm and 1000 ppm. As used herein, the term “substantially free of organic residuals” means that the composition exhibits residuals of 0.1 % (w / w) or less, in an embodiment, substantially free of organic residuals refers to a composition that exhibits residuals of 0.05% (w / w) or less. In an embodiment, substantially free of organic residuals refers to a composition that exhibits residuals of 0.01% (w / w) or less. In an embodiment, the amount of organic residuals is between 0 ppm (“non-detectable” or “ND”) and 1000 ppm. In an embodiment, the amount of organic residuals is ND to about 500 ppm. In an embodiment, the amount of organic residuals is ND to about 400 ppm. In an embodiment, the amount of organic residuals is ND to about 300 ppm. In an embodiment, the amount of organic residuals is ND to about 200 ppm. In an embodiment, the amount of organic residuals is ND to about 100 ppm. In an embodiment, the amount of organic residuals is between 10 ppm and 1000 ppm. Compositions of the present disclosure exhibit “biocompatibility” meaning that the compositions are compatible with living tissue or a living system by not being toxic, injurious, or physiologically reactive and not causing immunological rejection. Such biocompatibility can be evidenced by participants topically applying compositions of the present disclosure on their skin for an extended period of time. In an embodiment, the extended period of time is about 3 days. In an embodiment, the extended period of time is about 7 days, in an embodiment, the extended period of time is about 14 days, in an embodiment, the extended period of time is about 21 days. In an embodiment, the extended period of time is about 30 days. In an embodiment, the extended period of time is selected from the group consisting of about I month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, and indefinitely. Compositions of the present disclosure can be “hypoallergenic” meaning that they are relatively unlikely to cause an allergic reaction. Such hypoallergenicity can be evidenced by participants topically applying compositions of the present disclosure on their skin for an extended period of time. In an embodiment, the extended period of time is about 3 days. In an embodiment, the extended period of time is about 7 days. In an embodiment, the extended period of time is about 14 days. In an embodiment, the extended period of time is about 21 days. In an embodiment, the extended period of time is about 30 days. In an embodiment, the extended period of time is selected from the group consisting of about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, and indefinitely. In an embodiment, a peptide composition of the present disclosure has non- detectable levels of LiBr residuals. In an embodiment, the amount of the LiBr residuals in a composition of the present disclosure is between 10 ppm and 1000 ppm. In an embodiment, a peptide composition of the present disclosure has non- detectable levels of Na2CO3residuals. In an embodiment, the amount of the Na2CO3residuals in a composition of the present disclosure is less than 100 ppm. In an embodiment, the amount of the Na2CO3residuals in a composition of the present disclosure is less than 200 ppm. In an embodiment, the amount of the Na2CO3 residuals in a composition of the present disclosure is less than 300 ppm. In an embodiment, the amount of the Na2CO3 residuals in a composition of the present disclosure is less than 400 ppm. In an embodiment, the amount of the Na2CO3residuals in a composition of the present disclosure is less than 500 ppm. In an embodiment, the amount of the Na2CO3 residuals in a composition of the present disclosure is less than 600 ppm. In an embodiment, the amount of the Na2CO3residuals in a composition of the present disclosure is less than 700 ppm. In an embodiment, the amount of the Na2CO3residuals in a composition of the present disclosure is less than 800 ppm. In an embodiment, the amount of the Na2CO3 residuals in a composition of the present disclosure is less than 900 ppm. In an embodiment, the amount of the Na2CO3 residuals in a composition of the present disclosure is less than 1000 ppm. In an embodiment, the amount of the Na2CO3residuals in a composition of the present disclosure is non-detectable to 500 ppm. In an embodiment, the amount of the Na2CO3residuals in a composition of the present disclosure is non-detectable to 450 ppm. In an embodiment, the amount of the Na2CO3residuals in a composition of the present disclosure is non-detectable to 400 ppm. In an embodiment, the amount of the Na2CO3 residuals in a composition of the present disclosure is non-detectable to 350 ppm. In an embodiment, the amount of the Na2CO3 residuals in a composition of the present disclosure is non-detectable to 300 ppm. In an embodiment, the amount of the Na2CO3 residuals in a composition of the present disclosure is non-detectable to 250 ppm. In an embodiment, the amount of the Na2CO3 residuals in a composition of the present disclosure is non-detectable to 200 ppm. In an embodiment, the amount of the Na2CO3residuals in a composition of the present disclosure is non-detectable to 150 ppm. In an embodiment, the amount of the Na2CO3residuals in a composition of the present disclosure is non-detectable to 100 ppm. In an embodiment, the amount of the Na2CO3 residuals in a composition of the present disclosure is 100 ppm to 200 ppm. In an embodiment, the amount of the Na2CO3 residuals in a composition of the present disclosure is 200 ppm to 300 ppm. In an embodiment, the amount of the Na2CO3residuals in a composition of the present disclosure is 300 ppm to 400 ppm. In an embodiment, the amount of the Na2CO3residuals in a composition of the present disclosure is 400 ppm to 500 ppm. As used herein when referring to a number or a numerical range, the term “about” means that the stated number or numerical range is included together with numbers or numerical ranges within experimental variability, or within statistical experimental error from the stated number or numerical range, wherein the variation or error is from 0% to 15%, or from 0% to 10%, or from 0% to 5% of the stated number or numerical range. The silk proteins or fragments thereof, silk solutions or mixtures (e.g., SPF or SFS solutions or mixture), and the like, may be prepared according to the methods described in U.S. Patent Nos.9,187,538, 9,522,107, 9,522,108, 9,511,012, 9,517,191, 9,545,369, and 10,166,177, and U.S. Patent Publication Nos.2016 / 0222579 and 2016 / 0281294, and International Patent Publication Nos. WO 2016 / 090055 and WO 2017 / 011679, the entirety of which are incorporated herein by reference. Methods of using silk fibroin or silk fibroin fragments in coating applications are known and are described for example in U.S. Patents Nos.10,287,728 and 10,301,768. EXAMPLES The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the described embodiments, and are not intended to limit the scope of what the inventors regard as their invention nor are they intended to represent that the experiments below are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperature, etc.) but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Centigrade, and pressure is at or near atmospheric. Example 1: Scaleup Methods In some embodiments, a scaleup method comprises a lower gradient of temperature (Δ°) between any two points, two planes, or two voxels in a scaleup setup, e.g., and without limitation, a scaleup reaction vessel, compared to any similarly situated two points, two planes, or two voxels in a bench setup, e.g., and without limitation, a bench reaction vessel. In some embodiments, the scaleup gradient is lower than the bench gradient by about 1 °C, about 2 °C, about 3 °C, about 4 °C, about 5 °C, about 6 °C, about 7 °C, about 8 °C, about 9 °C, about 10 °C, about 11 °C, about 12 °C, about 13 °C, about 14 °C, about 15 °C, about 16 °C, about 17 °C, about 18 °C, about 19 °C, or about 20 °C. O W-4305-272230 cS7388380103880651ifeB0104313 tnee ye sttb gnvieo smnurn epmirts)rodwI )et ns eir dotnnaee )dDIDnIoitklnwtiaiSdn oi em(hgO RgCniO Rniti .dathcbrh Lcn3. (2 m(C m ga ny art et cn gmCe B59 L .81020106 L80602ah bxe awe0B00100401ssametap sep:slnop elmmovmetsnilns :s ometoa ovbr etitritm rererf nsavr nce ac re no tata eo oitmBioian trotoawm tuia itwwmit reuwcaelnL tulsesesbsxc t d t rt n n nme oioMoEoCxEoSxExEiRiRiRutNossNirbDiF 3s.s9 iD O W-430n5ier noi-d t2eorut a7t x r2230 detetkacan djoit yle gLanvinist ietfa niatio0i5btit tingor ganoimoepe a bif siitaenCro.rydbnallaelrru.iutdr eni d ot tugnt xiofmi 0nn ca in tm 6ioit eor dgreuniM. MnPoi-0 mcs ei0ae salrrmbodrebdRtca3 6 R gacusifda52er658n ideen sitasnytet ollaudufnrie ig nnd ka an la oitini nommirteck en eu itiB.y i alniniaaeat ntsreb3-0163eb nR Loecvo tomfm aoc5nideetsnyln se la iraetit onu duni n fnird k galoie ae nu ait tamnioit ecka ni B y in nieat.nltir b3- m0aeb n esoetm 16 R Locvomfaocemitn eoitmiatninboitmc soa etCeRoN Example 2: Derivatized / Modified Peptides A novel method is disclosed to generate compositions of polypeptides that are derived from B. mori silkworm cocoons and comprised of natural and modified polypeptides. These two novel compositions are called Low Skid and Mid Skid silk / modified polypeptide compositions. The novel production method involves removing sericin through several washing steps with an organic sodium carbonate salt with tightly controlled multi- stage temperature cycles and agitation as the first step in forming natural / modified polypeptide composition. Next the silk is dried to remove remaining water at controlled temperature to maintain polypeptide composition. The silk is then dissolved in high concentration of Lithium salt at two different temperatures and times to achieve the different compositions for Mid and Low silk. The liquid solution is then filtered and purified to remove the Lithium salt leaving only the natural / modified silk compositions in solution with pure water. Low Skid and Mid Skid silk / modified polypeptide compositions comprise of populations of silk / modified polypeptides with distinctive properties. Low Skid silk / modified polypeptide composition does not self-assemble at 5 mg / mL. Low Skid silk / modified polypeptide composition comprises of two main populations of silk / modified polypeptides; one population (AS22) that does not self-assemble under conditions that promote self-assembly at 5 mg / mL and is rich in negatively charged amino acids; a second population of polypeptides (AS12) that self-assemble fast at 5 mg / mL and are depleted on negatively charged amino acids. When AS12 and AS22 are combined at a ratio of 50% each the average molecular weight of the mixture becomes the same as Low Skid silk / modified polypeptide composition. Thus Low Skid silk / modified polypeptide composition consists of 50% AS12 and 50% AS22 silk / modified polypeptide compositions. Mid Skid silk / modified polypeptide composition comprises of two main populations of silk / modified polypeptides; one population (AS11) that self-assemble slower than Mid Skid silk / modified polypeptides, under conditions that promote self- assembly at 5 mg / mL and is rich in negatively charged amino acids; a second population of polypeptides (AS1) that self-assemble faster than Mid Skid silk / modified polypeptides, under conditions that promote self-assembly at 5 mg / mL and are depleted on negatively charged amino acids. DB1 / 147842605.187 When AS11 and AS1 are combined at a ratio of 50% each the average molecular weight of the mixture becomes the same as Mid Skid silk / modified polypeptide composition. Thus, Low Skid silk / modified polypeptide composition consists of 50% AS1 and 50% AS11 silk / modified polypeptide compositions. Both Low Skid and Mid Skid silk / modified polypeptide compositions contain modified peptides that were determined after analysis with Mass Spectrometry. Low and Mid Skid silk / modified polypeptide compositions described in this disclosure are never produced before compositions of silk-derived and modified polypeptides that when isolated display a wide range of behaviors, from extreme self- assembly to solubility and stability over time in various buffers and various average molecular weights and polydispersities. These novel silk-derived polypeptide compositions contain unique modified amino acid sequences that result from a unique silk processing method and scaleup. The tight controls around temperature, silk concentration, salt concentrations, physical agitation and purification allow us to tune at each step of the process the unique peptide compositions in the natural / modified silk species to design for specific performance criteria. Some of constituent polypeptide compositions display biological activity and could be used as therapeutic candidates. Silk is a versatile material that can be used in many applications from development of implantable medical devices to the development of soluble polypeptide formulations of medicinal value. A major challenge with silk polypeptides in solution is their tendency to self-assemble and aggregate, making the control of their solubility very difficult. Also, the kinetics of gel / film formation cannot be controlled in a predictable way. This novel silk / modified peptide compositions contain populations of peptides that allows to control their properties and develop products with predictable and desired properties. The disclosed compositions contain a collection of many polypeptides with different properties. Silk has been characterized mostly based on its molecular weight and polydispersity, and no mixture of silk / modified polypeptides has been characterized or has been generated. As disclosed herein, a unique large scale process is used to generate compositions of silk / modified polypeptides. Low / Mid skid silks begin their process to remove sericin using sodium carbonate at specific silk mass, sodium carbonate, and water ratios. Multiple different temperature washing cycles 100 °C and 60 °C and agitation is also key in producing DB1 / 147842605.188 the specific natural / modified compositions. The silk is then dried to remove water at a specific temperature that maintains the silk composition. Next the silk is dissolved in a high concentration of Lithium Bromide at 103 °C and 125 °C for 1 and 6 hours respectively. The time and temperature allow for fine tuning the degree of post translational modifications that give the unique polypeptide compositions. The silk is then purified to remove Lithium Bromide and optionally concentrate the silk. For the downstream characterization of isolation of the various silk / modified polypeptide compositions chromatographic techniques were employed, biochemical / biophysical techniques, and cell biology methods. To characterize / separate novel Low and Mid Skid silk / modified polypeptide compositions a combinations of Ion Exchange Chromatography fractionation, analytical methods, and biochemical dissection were used to characterize its properties. Generation of Low and Mid Skid silk / modified polypeptide compositions. Silk is washed to remove sericin at 100 °C and 60 °C with sodium carbonate and then dried at 60 °C. The silk is then dissolved in 9.3 M Lithium Bromide at 103 °C for 1 hour for Mid silk and 9.3 M Lithium Bromide at 125 °C for 6 hours for Low silk. This dissolution step controls not only molecular weight but also the polypeptide modifications creating the natural / modified silk compositions. The silk is then filtered to remove undissolved debris and purified using 10 KDa cutoff PES hollow fiber membranes, and concentrated using the same process leaving only natural / modified silk composite in solution with pure water. Every unit ops is tightly controlled for temperature, time, concentrations, agitation, and shear. Isolation of Low and Mid Skid / modified polypeptide compositions Isolation of the AS22 silk / modified polypeptide composition component of Low Skid silk / modified polypeptide composition. To isolate AS22 it was fractionated Low Skid silk / modified polypeptide compositions using HiTrap Q Sepharose Anion Exchanger (FIG.1 and FIG.2). Tris was added in the silk preparations to a final concentration of 50mM Tris-HCl pH=8.0. Silk was centrifuged before loading the HiTrap Q Sepharose column to remove any preformed aggregates. Low Skid silk preparation solutions have a characteristic yellow hue. The flow through from the HiTrap Q Sepharose column was transparent. AS22 eluted with 1M NaCl and it has an intense yellow hue. DB1 / 147842605.189 When AS22 formulation is analyzed with an analytical SEC column (see materials and methods) with HPLC it has an average molecular weight (MW) of about 35 kDa and Polydispersity (PDI) of 2.3 (FIG.3, FIG.4A, and FIG.4B ). This molecular weight and polydispersity are distinctive and different from Low Skid silk / modified polypeptide composition (MW about 19.5kDa and PDI 2.2) and Mid Skid silk / modified polypeptide composition (MW about 38kDa and PDI 2.4) (FIG.3, FIG.4A, and FIG.4B). When AS22 and Low Skid silk were analyzed in Isoelectric Focusing Polyacrylamide gels, it was found that 22M silk peptides had pIs 3-6 and some species with pIs of about 9.6, whereas Low Skid silk also contains peptides that span the whole range of pIs, from 3 to 9.6 (FIG.5). Isolation of the AS12 silk / modified polypeptide composition component of Low Skid silk / modified polypeptide composition. To develop AS12 a combination of Ion Exchange Chromatography (IEX) fractionation was used to purify the formulation, analytical methods and biochemical dissection to characterize its properties. To isolate AS12 Low Skid silk preparations was fractioned using HiTrap Q Sepharose Anion Exchanger (FIG.1 and FIG.2). Tris was added in the silk preparations to a final concentration of 50mM Tris-HCl pH=8.0. Silk was centrifuged before loading the HiTrap Q Sepharose column to remove any preformed aggregates. The flow through from the HiTrap Q Sepharose column was collected and was designated AS12. AS12 is colorless. AS12 silk formulation is composed of short silk / modified polypeptides depleted in negative charges. When AS12 was analyzed with analytical Size Exclusion Chromatography, it has an average molecular weight (MW) of about 12 kDa and Polydispersity (PDI) of 1.7 (FIG.3, FIG.4A, and FIG.4B). This molecular weight and polydispersity are distinctive and different from Low Skid silk / modified peptide composition (MW about 19.5 kDa and PDI 2.2) and Mid Skid silk / modified peptide composition (MW about 38 kDa and PDI 2.4) (FIG.3, FIG.4A, and FIG.4B). When AS12 and Low Skid silk / modified peptide composition were analyzed in Isoelectric Focusing Polyacrylamide gels, it was found that AS12 silk peptides had a pI of about 9-10, DB1 / 147842605.190 whereas Low Skid silk also contains peptides that span the whole range of pIs, from 3 to 9.6 (FIG.5) with most of them concentrated around pI 3-5.5. Isolation of the AS1 silk / modified polypeptide composition component of Mid Skid silk / modified polypeptide composition. To isolate AS1 Low Skid silk preparations were fractioned using HiTrap Q Sepharose Anion Exchanger (FIG.1 and FIG.2). Tris was added in the silk preparations to a final concentration of 50 mM Tris-HCl pH=8.0. Silk was centrifuged before loading the HiTrap Q Sepharose column to remove any preformed aggregates. The flow through from the HiTrap Q Sepharose column was collected and was designated AS1. AS1 has a MW of about 28kDa and PDI of 1.7-2.1 (FIG.3, FIG.4A, and FIG.4B). Mid Skid silk / modified peptide composition has MW of 37kDa PDI 2.0 (FIG.3, FIG.4A, and FIG.4B). Isolation of the AS11 silk / modified polypeptide composition component of Mid Skid silk / modified polypeptide composition. To develop AS11 a combination of Ion Exchange Chromatography (IEX) fractionation to purify the formulation, analytical methods and biochemical dissection to characterize its properties was used. To isolate AS11 Mid Skid silk / modified peptide composition preparations was fractionated using HiTrap Q Sepharose Anion Exchanger (FIG.1 and FIG.2). Tris was added in the silk preparations to a final concentration of 50 mM Tris-HCl pH=8.0. Silk was centrifuged before loading the HiTrap Q Sepharose column to remove any preformed aggregates. The elution from the HiTrap Q Sepharose column was collected and was designated AS11. AS11 formulation has a molecular weight (MW) of about 53 kDa and Polydispersity (PDI) of 2.8 (FIG.3, FIG.4A, and FIG 4B). This molecular weight and polydispersity are distinctive and different from Mid Skid silk / modified peptide composition (MW, about 37kDa and PDI 2.4) (FIG.3, FIG.4A, and FIG.4B). Self-Assembly of Low and Mid Skid / modified polypeptide compositions Self-assembly assay and data derived from it. To study the stability of AS1 in solution self-assembly assays was performed. AS1 silk at 5 mg / mL self assembles very fast. The absorbance at 550 nm curves of the self-assembly assays are sigmoid and they can be described as logistic curves. The typical logistic function is: ^^^^^ ^^^ ^^௫DB1 / 147842605.1 Amax is the maximum density of the gel formed k is the Self Assembly Rate Factor t0.5 is the time point at which 50% of the gel has formed e is the exponential equation for the specific curve Another parameter introduced to characterize the propensity of silk to form gels is the Self Assembly Factor which is: ^^ 1ௌ^ி =^^0.5( ^^ ^^ ^^)∗ ^^^^௫( ^^ ^^ ^^) ∗ 1000Using the performed with the various novel isolated and use to dissect their properties (FIG.6A-6B, FIG.7A-7C, FIG.8). Four parameters were in focus, collectively referred to as Self-assembly kinetic factors; the Self-Assembly Rate Factor (SARF), Amax, t0.5, and the Self Assembly Factor (SAF) (FIG.6A-6B, FIG.7A- 7C, FIG.8). The SARF shows how fast silk self-assembles to form gel after the reaction begins or the gelation nuclei have formed; Amax shows how dense is the gel that is formed after self-assembly is complete, t0.5 shows how long it takes for the self- assembly reaction to reach the point where gel density is Amax2 and SAF shows the propensity of silk to self-assemble (FIG.6A-6B, FIG.7A-7C, and FIG.8). AS1 silk / modified polypeptide composition has the fastest self-assembly kinetics. Self-assembly assays as described before, revealed that AS1 self-assembles very fast, much faster than Mid Skid silk / modified peptide compositions (FIG.6A-6B, FIG.7A-7C, and FIG.8). Mid Skid silk / modified peptide compositions was used as a positive control and shows fast self-assembly kinetics (FIG.6A-6B, FIG.7A-7C, and FIG.8). AS11 silk / modified polypeptide composition has the fastest self-assembly kinetics. Self-assembly assays as described before, revealed that AS11 self-assembles fast but not as fast as Mid Skid silk / modified peptide compositions (FIG.6A-6B, FIG. 7A-7C, and FIG.8). Mid Skid silk / modified peptide compositions was used as a positive control and shows fast self-assembly kinetics (FIG.6A-6B, FIG.7A-7C, and FIG. 8). DB1 / 147842605.192 AS12 silk / modified polypeptide composition is the component of Low Skid silk / modified polypeptide composition that promotes self-assembly. Self-assembly assays as described before, revealed that AS12 self-assembles fast but not as fast as Mid Skid silk / modified peptide compositions (FIG.6A, FIG.6B, FIG.7A-C, and FIG. 8). Mid Skid silk / modified peptide compositions was used as a positive control and shows fast self-assembly kinetics (FIG.6A-6B, FIG.7A-7C, and FIG. 8). AS22 silk / modified polypeptide composition is very stable in aqueous solution and doesn’t self-assemble. Self-assembly assays as described before, revealed that AS22 displays a remarkable stability and doesn’t self-assemble even in conditions that promote silk self-assembly. Mid Skid silk was used as a positive control and shows fast self- assembly kinetics (FIG.6A-6B, FIG.7A-C, and FIG. 8). When AS1, AS11, AS12 and AS22 silk / modified polypeptide compositions are combined at different ratios they result in compositions with unique properties. To better understand the properties of the silk / modified polypeptide compositions (FIG.6A-6B, FIG.7A-C, and FIG. 8) a series of mixtures were created (see table 1). The resulting compositions display a unique combination of properties in self-assembly assays (FIG.6A-6B, FIG.7A-C, and FIG. 8). Mixtures of AS1 and AS11 (AS2-10) and AS12 with AS22 (AS13-AS21) all display a unique combination of self-assembly kinetics (FIG.6A-6B, FIG.7A-C, and FIG. 8). This information can be used to create silk / modified polypeptide compositions with specific desired properties. Materials and Methods used for the generation and characterization of AS1-AS28. Anion Exchange Fractionation of Silk. Low Skid silk was provided at a concentration of 60 mg / mL. Low Skid silk was centrifuged at 20,000 x g, at 4°C for 15 min to remove any aggregated material. For the silk fractionation Q-Sepharose prepacked columns connected to an AKTA pure 25 L (Cytiva, Serial Number 2747908) or columns packed with Q-Big Beads resin (Cytiva) were used. All buffers used were filtered through a 0.45μm PES filter and degassed with sonication. Centrifuged Low or Mid Skid silk was loaded on 5 x 5mL HiTrap Q HP columns (Cytiva 17115401, Lot:10305274) washed with 10 DB1 / 147842605.193 column volumes of 50mM Tris pH=8.0, 10 column volumes of 50mM Tris pH=8.0 (Tris Base, Goldbio CAT# T-400-5, CAS# 77-86-1, Lot # 250501T400), 1M NaCl (NaCl, VWR High Purity Grade, X190-5kg, Lot # 20G2756431) and finally 10 column volumes of 50mM Tris pH=8.0.100mL of centrifuged Low Skid silk were loaded on the column with a flow rate of 5mL / min. The flow-through was collected. The column was washed with 50 mM Tris pH=8.0 until the absorbance at 280nm [A280] got to 100 AU. Bound protein was eluted in one step with 50mM Tris pH=8.0, 1M NaCl and all fractions with absorbance [A280] >500AU were pooled together. 20mL of the Low Skid silk (LS) that was used for the fractionation, the flow through (QFT) and the pooled elution fractions (QE) were placed in dialysis bags (Sigma D9652-100FT, Dialysis tubing cellulose membrane avg flat width 33mm, 1.3in., PCode1003241246, Lot#3110) and were immersed in 50 x volumes of 50mM Tris pH=8.0. Samples were flash frozen in liquid nitrogen and stored at -20°C until they were used. Before use samples were thawed slowly at 4 °C or on ice. Analytical / Protein Characterization methods. Protein concentration determination. Protein concentration was determined by absorbance at 220nm or 280nm. Solubilized silk preparations were diluted until A280 was between 0.1-1. In this range the absorbance correlates linearly with the concentration of silk in the solution and the correlation is 1AU=1mg / mL soluble silk proteins. Final concentrations in the initial silk solution were calculated after adjustment for the dilution used for the absorbance measurement. Analytical Size Exclusion Chromatography. Analysis was performed in a PolySep GFC P-4000 LC Column, 300 mm x 7.8 mm (Phenomenex, Part No. CH0-9229) connected to a Agilent 1260 Infinity II HPLC system with an Agilent G7162A RID Refractive Index Detector. The mobile phase used for the analysis was a solution of 0.1M NaCl, 12.5mM Na2HPO4, pH 7 (the pH was adjusted with phosphoric acid and filtered through a 0.2μm PES filter into a clean glass media bottle).25μL of sample were loaded on the column and the analysis was performed at 25 °C with a flow rate of 1mL / min for 20min. Calculation of the molecular weight of each sample was done using Agilent Technologies Open LAB CDS ChemStation Edition for LC & LC / MS Systems software Cirrus SEC data collection and molecular weight analysis software. DB1 / 147842605.194 Analytical Anion Exchange Chromatography. For the analysis an HPLC Dionex Ultimate 3000 and a TSKgel (07163) DEAE-3SW column 7.5mm ID x 7.5cm, 10μm was used. Chromatography was performed at 25°C.10% Trifluoroethanol, 45% Acetonitrile in water was used as a blank solution. The column was equilibrated with 20mM Na2HPO4 / KH2PO4 (Na2HPO4: Fisher Chemical, Lot# 188298, PN# S374-500, KH2PO4: Fisher Chemical, Lot# 187270, PN# P285-500), pH 6 at 1 mL / min for 10 min.30μL of sample were loaded on the column. Bound silk polypeptides were eluted with a linear gradient of 500mM NaCl (NaCl: Fisher Chemical, Lot# 206719, PN# BP358-1). All solutions were made in LCMS water: Fisher Chemical, Lot# 216650, PN# W5-4. Collected data were analyzed with XCaliburTMSoftware. Isoelectric Point determination of silk. To determine the isoelectric point of the new silk compositions Isoelectric Focusing gels were used. These separate proteins based on their net charge and not their molecular weight. For the analysis, a BIO-RAD Criterion Precast Gels was used, IEF standards pI 4.45-9.6 (BIO-RAD, Cat#1610310, Batch 64417452, L0040178). Silk protein samples from new silk compositions were mixed with IEF Sample Buffer (BIO-RAD Cat # 16110763, Batch 64345676, L004138B) (making sure to have at least 5% v / v glycerol in the final mix). The mixtures were loaded on a Criterion Precast Gel. For the electrophoresis a 1x IEF Anode Buffer (BIO-RAD Cat # 1610761, Batch 64376614) and 1x IEF Cathode Buffer (BIO-RAD, Cat # 1610762, Batch 64364827) were used. The running conditions for the electrophoresis were: 100V constant for 60min, 250V constant for 60min and 500V constant for 30min. After the electrophoresis was complete proteins were fixed on the gel with a solution of 40% v / v Methanol (Sigma Aldrich, Methanol ACS reagent >99.8%, 179337-4L-Pb,Source SHBN0806, Pcode 1003210445), 10% v / v Acetic acid (VWR Acetic Acid, Glacial, ACS Grade, BDH3092-500MLP, Lot: 2018071399), for 30min to overnight at room temperature with rocking. LC / MS analysis of polypeptides. Samples were stored at 4°C until used for analysis. For each sample, an aliquot was taken and mixed with an equal volume of 6 M guanidine hydrochloride (GuHCl) in a new tube. From that mix, an aliquot was taken again to create 120-fold and 240- fold further dilutions for determining protein concentrations using the BCA assay. DB1 / 147842605.195 Using the concentrations determined above, samples were diluted to 20μg / μL with 6 M GuHCl. An aliquot of 1,000μg total protein was transferred to a new tube.50 mM dithiothreitol (DTT) was added to a final concentration of 5mM and the samples were incubated at 60°C for 30 minutes. After a brief equilibration period to room temperature, 100mM iodoacetamide (IAM) was added to a final concentration of 10mM and the samples were incubated at room temperature in the dark for 30 minutes. The IAM reaction was quenched by the addition of 50mM DTT to a final concentration of 5mM DTT, followed by a further incubation at room temperature for 30 minutes. Three aliquots corresponding to 100μg of total protein were taken in separate tubes and diluted in PBS to get a final concentration of 0.2M GuHCl. Samples were then treated with enzyme at a protease to protein ratio of 1:50 (2μg of each protease) overnight at either room temperature (chymotrypsin) or 37°C (trypsin / Lys-C and Glu-C). The protease reactions were quenched by the addition of TFA to a final concentration of 1% (v / v). Samples were centrifuged for 10minutes at 14,000rpm and supernatant was transferred to HPLC autosampler vials for LC-MS analysis. LC Column: C18 column (100 μm x 150 mm, 3 μm) Mobile Phase A: Water 0.1% formic acid Mobile Phase B: Acetonitrile 0.1% formic acid Flow Rate: 600nL / min (micro pump) and 15μL / min (loading pump) Chromatographic time: 60 minutes Elution Gradient: 7% B (0 to 3.3 min); 7% to 35% B (3.3 to 35 min); 35% to 95% B (35-37 min); 95% to 80% B (37-39 min); 80% B (39-41 min); 80% to 7% B (41 to 44 min); 7% B (44 to 60 min) Injection volume: 4 μL Acquisition for full MS ranges from 350 to 1600m / z. The MS method is based on data-dependent acquisition (DDA) for the top 10 ions with an isolation window of 3.0m / z and a normalized collision energy of 26. Data was acquired using Thermo XcaliburTM Software. Data analysis was performed using Thermo Proteome DiscovererTM Software. To unequivocally assign a specific protein from the identified peptides, a minimum of 2 unique peptides per protein are required upon searching against SwissProt database. Gel Staining methods. DB1 / 147842605.196 Silver Staining SDS and IEF polyacrylamide gels were stained using ProteoSilver Silver Stain Kit (Sigma, PROTSIL-1-1KT, Lot # SLCH2293, Pcode: 1003135372) following the manufacturer’s instructions. Briefly, gels were immersed in fixing solution (50% v / v Ethanol, 10% Glacial Acetic Acid), washed with water, sensitizer solution, silver solution and developer solution. Gel band development was terminated with ProteoSilver Stop Solution. Self Assembly Assay. The silk Self Assembly Assay (SAF) was performed in 35% v / v 2-propanol (Sigma-Aldrich 2-Propanol ACS reagent >99.5%.190764-4L, Lot # SHBK7164, PCode 1002789344) and 50mM CH3COONa pH=5 (Sodium acetate anhydrous, VWR life sciences Product number 0602-1Kg, Lot # 0677C055). Each reaction was done in a final volume of 200μL. Total silk protein concentration was 5mg / mL. First the buffer of 50mM CH3COONa pH=5, 35% v / v 2-propanol was prepared. Then DI / RO water was added so that after the addition of the volume of silk protein required to reach a final concentration of 5mg / mL the total volume would be 200μL. The protein was added last and mixed with very gentle pipetting to reduce shearing force. The protein mixtures were placed in wells of flat-bottom 96-well plates and a layer of 100μL of Mineral Oil (Sigma, Mineral Oil BioReagent, for molecular biology, light oil, M5904- 500mL, Lot # MKCC7596, PCode 1002883254) carefully so as to not create any bubbles. Absorbance was recorded at 550nm for 16-24h (depending on the sample). Recorded values were exported in Excel files for storage and further analysis. Data analysis. Data were analyzed using GraphPad Prism 9 for macOS Version 9.2.0 (283), July 15, 2021. Figures were prepared with Adobe illustrator 25.4.1. Table 1. Detailed composition of all AS products generated herein. The composition of each product is given in % per mass (mg / mL). AS Low Skid Q- Low Skid Q Flow Mid Skid Q- Mid Skid Q Flow DB1 / 147842605.197 3 0 0 80 20 4 0 0 70 30 Fibroin isolation DB1 / 147842605.198 Fibroin isolation requires separation of sericin from raw B. mori silk fibers. This separation was carried out in a single stage and facilitated in a solid extraction operation. The unit was comprised of an atmospheric vessel enclosing a perforated drum which rotates on a horizontal axis. Before loading the raw silk fibers into the rotating drum via a sealable access port, silk cocoons were packed loosely into permeable mesh bags. This primary containment minimizes product loss, protects the equipment by preventing rogue silk strands from entangling with rotating components in the vessel, and protects the drain lines from plugging with solids that would otherwise escape from the drum during processing. The vessel was filled with extraction solvent comprised of 0.7% - 0.95% wt. (typically 0.94% wt.) sodium carbonate in water to partially submerge the perforated drum. This solvent composition was shown effective at dissolving and stabilizing sericin in solution. The cocoon / solvent ratio was 0.040 kg / kg – 0.070 kg / kg (typically 0.042 kg / kg). An electric heater located at the base of the vessel was used to maintain temperature of the extraction solvent in the range of 94.5°C – 97°C. Maintaining the extraction solvent at elevated temperature drives sericin solvation. Secondarily, the elevated temperature thermally cleaves fibroin chains to reduce average molecular weight of the protein population. The rotating drum turned periodically throughout a 30-minute isothermal phase of the extraction. This action serves to expose all fiber surfaces to the extraction solvent. Rinsing with copious hot water followed. The vessel was filled with non-potable water to partially submerge the perforated drum. Rinse water temperature was maintained in the range of 55°C – 65°C for 20 minutes with intermittent drum rotation, then the rinse water was drained to waste. This was repeated two additional times. Once rinsed, the drum rotated at high speed to remove water retained in the cocoons by centrifugal action. Damp fibroin with moisture content from 15% - 65% wt. (average 46.74%) was then manually removed from the washer and distributed evenly onto perforated trays. The residual moisture was driven off the fibroin by storage in a dryer with internal temperature maintained at 55°C - 60°C until moisture content of the material was less than 1% of the total mass. Extraction efficacy was verified by measuring the change in mass of the dry material before and after processing in the extraction unit. Typically, the amount of sericin removed from the cocoons is 30-36% wt. of the total mass of the raw cocoons. The DB1 / 147842605.199 composition of the raw cocoons was characterized by LCMS. The method screened for chorion, fibrohexamerin (P25), heavy chain fibroin, light chain fibroin, sericin, and trypsin inhibitor. Using LCMS, sericin concentration in raw cocoons was determined to be ~35.27% wt. Sericin was undetectable in fibroin after processing in the extraction unit. This result suggests that the sericin extraction method is effective, and the fraction of sericin detected in the raw cocoons corresponds well with the observed mass loss of the cocoons in the field. Change in the relative abundance of heavy chain fibroin versus light chain fibroin in the isolated fibroin was also observed. In raw cocoons, the ratio of heavy chain fibroin to light chain fibroin was determined to be 1.13 kg / kg. Following sericin extraction, the ratio was in the range of 0.4-0.8 kg / kg. This reduction in the relative abundance of heavy chain fibroin suggests efficacy of the extraction process in thermally facilitated cleaving of the fibroin chains prior to solvation and modification. Fibroin solvation and modification Control over the solubilization and modification of fibroin was achieved by dispersing the solid protein into a solvent and thermally treating the mixture at variable time and temperature. Typically, a 9.3 M lithium bromide solution in water was used as a solvent. The solvent was prepared in a vessel with or without baffles. The solution was blended to uniformity in the vessel using a center-mounted agitator with stacked 45° pitched blade turbines. Heat transfer oil circulates through the vessel jacket to stabilize bulk fluid temperature at the required reaction temperature while the solvent mixes. Typically, the reaction temperature was stabilized in the ranges of 100°C – 103°C (103°C target) or 122°C - 125°C (125°C target). Fibroin was loaded into the vessel through an access port in the vessel head once the solvent reached the required reaction temperature. The mass ratio of fibroin to solvent was typically 0.16 kg / kg. Since the solvent density significantly exceeds the density of the dried fibroin, achieving full dispersion of the fibroin into the solvent is nontrivial. Substantial downward force was applied to the floating protein mat to fully submerge the material and clear the headspace for additional material to be added. Once the headspace was cleared, agitation was briefly employed to disperse the wetted silk mat before addition is continued. Loading the vessel with the full mass of fibroin occurs over the course of 40-60 minutes, during which time reaction temperature is maintained in the vessel. DB1 / 147842605.1100 The reaction time begins after the fibroin addition is completed. Agitation was carried out over the full course of the reaction period. Reaction time varied depending on the desired properties of the resulting solution. To produce Activated Silk™ 33B (Mid MW Activated Silk™), the reaction was carried out for 0 – 60 minutes with working fluid temperature held at 100° C – 103°C. FIG.9 displays the typical evolution of the average molecular weight of the solubilized fibroin as a function of reaction time for Activated Silk™ 33B. To produce Activated Silk™ 27P (Low MW Activated Silk™), the reaction was carried out for 40 – 420 min with temperature held at 122°C – 125°C. FIG.10 displays the typical evolution of the average molecular weight of the solubilized fibroin as a function of reaction time for Activated Silk™ 27P. The contents of the vessel are subsequently cooled. Cooling was accomplished by either of two methods. In one method, cooling was carried out by immediate removal of the solution from the vessel, dividing the solution into small volumes, and storing the containers in a refrigerator held at 4°C. In another method, cooling was carried out in place by recirculating chilled heat transfer oil through the vessel jacket. If cooling using a jacketed vessel, the temperature may be reduced to below 60°C within 70 minutes of the reaction period elapsing. Cooling to room temperature from 60°C may be carried out more slowly by environmental radiation or by forced cooling. When using forced cooling, the solution can be brought to room temperature within 3 hours. Activated Silk™ Purification The cooled reaction mixture is a viscous liquid comprised of water, stabilizing salt (typically LiBr), fibroin, and miscellaneous undissolved organic solids. Fibroin must be isolated from this mixture. Purification occurs through three filtration stages. First, the reaction mixture underwent dead-end filtration through a needle felt polypropylene filter media with nominal particle size rejection in the range of 1 µm – 200 µm to remove relatively large undissolved contaminants. The filtered reaction mixture was transferred through the filtration media to a holding vessel with or without baffles, which was pre-charged with some volume of reverse osmosis / de- ionized (RODI) water. The volume of water charged to the holding vessel was determined by multiplication of the reaction mixture volume against a water-to- reaction mixture volumetric ratio. This ratio ranges from 1 – 7 L / L depending on the desired product and required downstream processing conditions. DB1 / 147842605.1101 The reaction mixture was blended to uniformity with the dilution water using a center- mounted agitator with stacked 45° pitched blade turbines or a propeller. Chilled propylene glycol circulates through the vessel jacket to cool the diluted mixture if the diluted material was stored for greater than 24 hours. Agitation for blending was limited to the bare minimum to achieve homogeneity, as excessive or prolonged shear on the fluid increases risk of product loss due to precipitation or foaming. The diluted reaction mixture underwent additional dead-end filtration through either a melt-blown and spun-bonded pleated poly propylene media with nominal 0.2 µm rejection or a resin bonded cellulose / diatomaceous earth lenticular media with absolute 2.5 µm rejection to reduce solution turbidity below a desired threshold. The diluted reaction mixture was transferred through the filtration media to a tangential flow filtration (TFF) unit outfitted with a jacketed retentate vessel, a rotary lobe pump, 10 kDa molecular weight cutoff hollow fiber ultrafiltration membranes, and an automatically controlled backpressure valve used to stabilize transmembrane pressure (TMP) during processing. TMP is defined as the average internal pressure of the TFF unit minus the permeate line pressure. The diluted reaction mixture recirculated between the retentate vessel and the membrane bank via the lobe pump and backpressure valve. The pump operated to maintain a constant recirculation flowrate, typically in the range of 200 – 500 L / min depending on application. The backpressure valve was actuated to maintain TMP in the range of 7 – 18 psig depending on application. Chilled or heated propylene glycol or water was circulated through the retentate vessel to maintain working fluid temperature between 20°C and 35°C depending on application. Operating under these conditions drives permeation of water, LiBr, and smaller fibroin fragments through the membrane selective layers to waste. The majority of the dissolved fibroin was retained by the membranes. The TFF operation began diafiltration, where volume was maintained in the retentate vessel by backfilling with RODI water during as volume was lost to membrane permeate. Diafiltration conditions were maintained until the conductivity of the permeate dips below a desired threshold, typically 10 - 50 µS / cm. Critically, LiBr concentration must be below 150 ppm. Diafiltration ceases once this condition is satisfied, at which point RODI water flows to the system stops and the working fluid is allowed to concentrate as permeation continues under maintained TMP and flow conditions. Protein DB1 / 147842605.1102 concentration was monitored over the course of the concentration phase of operation. Concentration conditions were maintained until the protein concentration was within the range of 5 – 17% wt, depending on application. Total residence time in the TFF unit ranged from 12 – 35 hours depending on application. The purified Activated Silk™ solution was drained from the TFF unit and stored in either HDPE carboys or stainless-steel totes. The Activated Silk™ solution was stored at 4°C to maximize shelf life. Process development resulted in product yield improvements. Relative to the existing processes, yield was increased by ~100x for Activated Silk™ 27P and ~40x for Activated Silk™ 33B when the purification train was initially scaled up, then further increased by 1.75x for Activated Silk™ 27P and 2.9x for Activated Silk™ 33B when the processing techniques matured further. Additionally, process development has resulted in significant quality improvements exemplified by reduced variation in critical quality parameters, specifically in measurement of weight average molecular weight and dispersity characteristics of the protein population in the final product. In reference to previous processes, the first instance of scaleup work resulted in a 58% reduction in the standard deviation of molecular weight measurements and a 31% reduction in the standard deviation of dispersity measurements for Activated Silk™ 27P. In reference to previous processes, the first instance of scaleup work also resulted in a 29% reduction in the standard deviation of molecular weight measurements and a 59% reduction in the standard deviation of dispersity measurements for Activated Silk™ 33B. In reference to previous processes, the second instance of scaleup work resulted in a 64% reduction in the standard deviation of molecular weight measurements and a 12% reduction in the standard deviation of dispersity measurements for Activated Silk™ 27P. In reference to previous processes, the second instance of scaleup work also resulted in a 75% reduction in the standard deviation of molecular weight measurements and a 70% reduction in the standard deviation of dispersity measurements for Activated Silk™ 33B. Example 4. High Molecular Weight Silk Preparation Fibroin isolation Fibroin isolation requires separation of sericin from raw B. mori silk fibers. This separation was carried out in a single stage and facilitated in a solid extraction DB1 / 147842605.1103 operation. The unit was comprised of an atmospheric vessel enclosing a perforated drum which rotated on a horizontal axis. Before loading the raw silk fibers into the rotating drum via a sealable access port, silk cocoons were packed loosely into permeable mesh bags. This primary containment minimized product loss, protected the equipment by preventing rogue silk strands from entangling with rotating components in the vessel, and protected the drain lines from plugging with solids that would otherwise escape from the drum during processing. The vessel filled with extraction solvent comprised of 0.705 % sodium carbonate in water to partially submerge the perforated drum. This solvent composition has been shown effective at dissolving and stabilizing sericin in solution. The cocoon / solvent ratio was 0.068 kg / kg. An electric heater located at the base of the vessel was used to maintain temperature of the extraction solvent in the range of 94.5°C – 97°C. Maintaining the extraction solvent at elevated temperature drives sericin solvation. Secondarily, the elevated temperature thermally cleaves fibroin chains to reduce average molecular weight of the protein population. The rotating drum turned periodically throughout a 30-minute isothermal phase of the extraction. This action served to expose all fiber surfaces to the extraction solvent. Rinsing with copious hot water follows. The vessel was filled with non-potable water to partially submerge the perforated drum. Rinse water temperature was maintained in the range of 55°C – 65°C for 20 minutes with intermittent drum rotation, then the rinse water was drained to waste. This was repeated two additional times. Once rinsed, the drum rotated at high speed to remove water retained in the cocoons by centrifugal action. Damp fibroin with moisture content from 15% - 65% wt. (average 46.74%) was then manually removed from the washer and distributed evenly onto perforated trays. The residual moisture was driven off the fibroin by storage in a dryer with internal temperature maintained at 55°C - 60°C until moisture content of the material was less than 1% of the total mass. Fibroin solvation and modification Control over the solubilization and modification of fibroin was achieved by dispersing the solid protein into a solvent and thermally treating the mixture at variable time and temperature. A 9.3 M lithium bromide solution in water was used as a solvent. To produce High MW Activated SilkTM, 400 mL of solvent were added to two 4 L glass beakers. The beakers were then placed into an oven set to 160°C and allowed to DB1 / 147842605.1104 heat until the solvent temperature is 100°C ± 4°C. Once the solvent temperature was stabilized, 100 g of dried fibroin was added to each beaker and fully wetted with solvent by manual agitation with a stainless-steel spatula. The beakers were then placed back into the oven set to 160°C and allowed to remain in the oven for 15 – 60 min, depending on the required product characteristics. Solvent temperature was continuously monitored to ensure that the solvent temperature was maintained at 100°C ± 5 °C for the duration of the reaction period. The beakers were removed from the oven after the required reaction period. The beakers were allowed to cool for 30 - 60 min at ambient temperature. Undissolved solids in the beakers were removed. The volume of remaining liquid in the beakers was then measured into a sealed container and stored in a refrigerator at 4°C. Activated SilkTMPurification The cooled reaction mixture was a viscous liquid comprised of water, LiBr, fibroin, and minute undissolved organic solids. Fibroin must be isolated from this mixture. First, the reaction mixture was diluted into reverse-osmosis / deionized (RODI) water. The diluted mixture was brought infirmity by manual agitation of the dilution vessel, which was typically a sealable 5 gal BPA-free carboy. The volumetric ratio of reaction mixture to RODI water was 0.0562 mL / mL. The diluted reaction mixture then underwent dead-end filtration through a pleated glass fleece filter media with absolute 0.65 μm particle size rejection to remove minute undissolved solids and reduce solution turbidity. The diluted reaction mixture was transferred through the filtration media to a tangential flow filtration (TFF) unit outfitted with a retentate vessel (typically a sealable 50 L polypropylene carboy), a variable speed diaphragm pump, 10 kDa molecular weight cutoff hollow fiber ultrafiltration membranes, and a manually actuated backpressure valve used to stabilize transmembrane pressure (TMP) during processing. TMP was defined as the average internal pressure of the TFF unit minus the permeate line pressure. The diluted reaction mixture recirculated between the retentate vessel and the membrane bank via the diaphragm pump and backpressure valve. The pump was manually operated to maintain a constant 10 psi pressure drop across the membrane module. The backpressure valve was manually actuated to maintain TMP in the at approximately 35 psi. DB1 / 147842605.1105 Operating under these conditions drives permeation of water, LiBr, and smaller fibroin fragments through the membrane selective layers to waste. The majority of the dissolved fibroin was retained by the membranes. The TFF operation began diafiltration, where volume was maintained in the retentate vessel by backfilling with RODI water during as volume was lost to membrane permeate. Diafiltration conditions were maintained until the conductivity of the permeate dipped below a desired threshold, typically 10 - 50 μS / cm. Critically, LiBr concentration must be below 150 ppm. Diafiltration ceases once this condition is satisfied, at which point RODI water flow to the system stops and the working fluid is allowed to concentrate as permeation continues under maintained TMP and flow conditions. Protein concentration was monitored over the course of the concentration phase of operation. Concentration conditions were maintained until the protein concentration was within the range of 5 - 7%wt. The purified Activated SilkTMsolution was drained from the TFF unit and stored in either HDPE carboys or stainless-steel totes. The Activated SilkTMsolution was stored at 4°C to maximize shelf life. Example 5. Low and Mid Skid Silks Degree of Amino Acid Modifications. Low and Mid Skid silk polypeptide compositions described herein are never produced before compositions of silk-derived and modified polypeptides that when isolated displayed a wide range of behaviors, from extreme self-assembly to superb solubility and stability over time in various buffers and various average molecular weights and polydispersities. These novel silk-derived polypeptide compositions contain unique modified amino acids that result from unique silk processing method and scale. The tight controls around temperature, silk concentration, salt concentrations, physical agitation and purification allow for tuning at each step of the process the unique peptide compositions in the silk species to design for specific performance criteria. Some of constituent polypeptide compositions display biological activity and could be used as therapeutic candidates. Silk is a versatile material that can be used in many applications from development of implantable medical devices to the development of soluble polypeptide formulations of medicinal value. A major challenge with silk polypeptides in solution is their tendency to self-assemble and aggregate, making the control of their solubility very difficult. Also, the kinetics of gel / film formation cannot be controlled in a predictable way. The novel silk peptide compositions described herein contain populations of peptides that allow for the DB1 / 147842605.1106 control of their properties and allow for the development products with predictable and desired properties. Development of Low and Mid Skid silk / modified polypeptide compositions. Activated silk contains a collection of many polypeptides with different properties. Silk has been characterized mostly based on its molecular weight and polydispersity. Until now, no mixture of silk polypeptides has been characterized or has been generated. A unique large-scale process was used to generate compositions of silk polypeptides. Low / Mid skid silks began their process to remove sericin using sodium carbonate at specific silk mass, sodium carbonate, and water ratios. Multiple different temperature washing cycles 100°C and 60°C and agitation was also key in producing the specific natural and modified compositions. The silk was then dried to remove water at a specific temperature that maintained the silk composition. Next the silk was dissolved in a high concentration of Lithium Bromide at 103°C and 125°C for 1 and 6 hours, respectively. The time and temperature allow for fine tuning the degree of post translational modifications that give the unique polypeptide compositions. The silk was then purified to remove Lithium Bromide and concentrate the silk. Generation of Low and Mid Skid silk / modified polypeptide compositions. Silk was washed to remove sericin at 100°C and 60°C with sodium carbonate and then dried at 60°C. The silk was then dissolved in 9.3 M Lithium Bromide at 103°C for 1 hour for Mid silk and 9.3 M Lithium Bromide at 125°C for 6 hours for Low silk. This dissolution step controls not only molecular weight but also the polypeptide modifications creating the natural / modified silk compositions. The silk was then filtered to remove undissolved debris and purified using 10 kDa cutoff PES hollow fiber membranes and concentrated using the same process leaving only natural / modified silk composite in solution with pure water. Every unit ops was tightly controlled for temperature, time, concentrations, agitation, and shear. The silk preparations have unique modifications depending on the production method.The dissolution of degummed silk cocoons was performed in high concentration of chaotropic salts (9M LiBr) and at very high temperatures that exceed 100°C. The unique thermal treatment that occurs during the production method described herein, promotes the deamidation of Asparagine and Glutamine residues and the oxidation of Methionines. The deamidation of Asparagine and Glutamine residues and the oxidation of Methionines is referred to as “modifications” from now on. To DB1 / 147842605.1107 determine the degree of amino acid modification during the various silk preparation methods LC / MS approaches were used. When Low Skid Silk was compared with Mid Skid silk produced, it was found that Low Skid silk was more modified than Mid Skid silk (FIGS. 12A- 12C, Table A). When silk produced was lyophilized it retained the same modification trend; lyophilized Low Skid silk was more modified than lyophilize Mid Skid silk (FIGS.13A-13B, Table B). Low Skid silk produced in one facility unique and less modified than the Low Skid silk produced in another (FIGS. 14A- 14B, Table C). When silk was produced using a benchtop setup, the resulting silk preparation was less modified compared to its Skid counterpart (FIGS. 15A-15D, comparing Mid Skid silk with Mid Benchtop silk). LC / MS analysis of polypeptides. Materials Reagents ● Guanidine hydrochloride (GuHCl) (Sigma cat# G3272-1KG) ● Dithiothreitol (DTT) (ThermoFisher cat# 20290) ● Iodoacetamide (IAM) (Sigma cat# I1149-5G) ● HPLC-grade water (FisherChemical cat# W5-4) ● Acetonitrile (ACN) (FisherChemical cat# A955-4) ● Formic acid (FA) (FisherChemical cat# A117-10X1AMP) ● Trifluoroacetic acid (TFA) (FisherChemical cat# A116-10X1AMP) ● Sodium acetate (Sigma cat# S5636-250G) Proteases ● Trypsin / Lys-C mix (Promega cat# V5073) ● Chymotrypsin (Promega cat# V1061) ● Glu-C (Promega cat# V1651) Solutions ● 6 M GuHCl DB1 / 147842605.1108 ● 50 mM DTT (10X) ● 100 mM IAM (10X) ● 50 mM sodium acetate Denaturation, Reduction and Alkylation Samples were stored at 4°C until used for analysis. For each sample, an aliquot was taken and mixed with an equal volume of 6 M guanidine hydrochloride (GuHCl) in a new tube.50 mM dithiothreitol (DTT) was added to a final concentration of 5 mM and the samples were incubated at 60°C for 30 minutes. After a brief equilibration period to room temperature, 100 mM iodoacetamide (IAM) was added to a final concentration of 10 mM and the samples were incubated at room temperature in the dark for 30 minutes. The IAM reaction was quenched by the addition of 50 mM DTT to a final concentration of 5 mM DTT. The samples were diluted in 50 mM sodium acetate to get a final concentration of 0.18 M GuHCl. Protease digestion Using the sample concentrations provided, 3 aliquots corresponding to 30 μg of total protein were taken in separate tubes. Samples were then treated with enzymes at a protease to protein ratio of 1:30 (1 μg of each protease) overnight at either room temperature (chymotrypsin) or 37°C (trypsin / Lys-C and Glu-C). The aliquots treated with trypsin / Lys-C and Glu-C were boosted with the same amount of enzyme and incubated at 37°C for 3 hours the next day. The protease reactions were quenched by the addition of TFA to a final concentration of 1% (v / v). Samples were centrifuged for 10 minutes at 14,000 rpm and supernatant was transferred to HPLC autosampler vials for LC-MS analysis. LC Conditions Column: C18 column (100 μm x 200 mm, 3 μm) Mobile Phase A: Water 0.1% formic acid Mobile Phase B: Acetonitrile 0.1% formic acid Flow Rate: 300 nL / min (micro pump) and 15 μL / min (loading pump) Chromatographic time: 60 minutes DB1 / 147842605.1109 Elution Gradient: 14% B (0 to 3.3 min); 14% to 30% B (3.3 to 35 min); 30% to 95% B (35-37 min); 95% to 80% B (37-39 min); 80% B (39-41 min); 80% to 14% B (41 to 44 min); 14% B (44 to 60 min) Injection amount: 2 ug MS Conditions Acquisition for full MS ranges from 350 to 1600 m / z. The MS method is based on data- dependent acquisition(DDA) for the top 10 ions with an isolation window of 3.0 m / z and a normalized collision energy of 27. Data Acquisition and Analysis Data was acquired using Thermo XcaliburTMSoftware. Data analysis was performed using Thermo Proteome DiscovererTMSoftware. In order to unequivocally assign a specific protein from the identified peptides, a minimum of 2 unique peptides per protein are required upon searching against Bombyx mori database. For each modification site, all the peptides containing that amino acid were categorized into modified vs unmodified. The modification percentage is then calculated using the formula below: ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ % = ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^ ^^Table 2. Percentage of amino acid modifications in Low and Mid Skid silk produced in the facility in Walpole. N are Asparagines that become aspartic acid and Q are Glutamines that become deamidated. M corresponds to Methionies that become oxidized. Fibroin Heavy Chain N68 N70 N77 N93 N132 N5262 Q58 Q139 Q275 Q5216 M64 LS W l l 9537 9299 8533 3373 6908 21 356 1597 401 698 8654 .7 Fibroin Light Chain N23 N28 N108 N118 N136 N186 N200 N204 N240 N248 Q24 Q149 Q202 L l l 2 2 44 4 4 2 1 44 4 1 4 .16 .58 Fibrohexamerin (p25) DB1 / 147842605.1110 N93 N149 N172 N174 N202 LS Walpole 9.76 59.34 74.42 15.42 20.19 k produced in the facility in Walpole and lyophilized. N are Asparagines that become aspartic acid and Q are Glutamines that become deamidated. M corresponds to Methionies that become oxidized. Fibroin Heavy Chain N68 N70 N93 N132 N5262 Low Skid L o 100 100 1187 8634 3913 g N28 N105 N108 N136 N200 N204 N240 N248 Q255 02 .4 Table 4. Percentage of amino acid modifications in Low Skid silk produced in the facility in Walpole and Medford. N are Asparagines and Q are Glutamines that become deamidated. M corresponds to Methionies that become oxidized. Fibroin Heavy Chain N70 N132 N4191 Q125 Q275 Q5216 DB1 / 147842605.1111 Table 5. Percentage of amino acid modifications in Mid silk produced in Skid and Benchtop scale. N are Asparagines that become aspartic acid and Q are Glutamines that become deamidated. M corresponds to Methionies that become oxidized. Fibroin Heavy Chain N68 N4191 Q113 Q125 Mid Skid Walp 94.29 100 7.07 17.95 7 modification per location along the amino acid sequence of each protein chain. To determine the percentage of modified amino acids within the sequences of individual protein chains in the silk preparations, LC / MS analysis was employed. Through this analytical method, it was not only discerned the sequence of all peptides present in the solution but also quantified their respective concentrations. LC / MS methodology possesses the capability to pinpoint amino acid modifications at specific positions within these sequences, a phenomenon induced by the production techniques. Upon successfully identifying and quantifying all the peptides within the mixture, they were aligned with the protein sequences present in the silk cocoons. This alignment process allowed for the ascertainment of the origin of each peptide along the polypeptide chain of fibroin heavy and light chains, as well as fibrohexamerin (p25). Consequently, the exact positions of amino acids were pinpointed on these polypeptide chains. To calculate the percentage of modified amino acids at specific locations, all peptides containing these amino acids were quantified, both modified and unmodified. The calculation involved dividing the quantity of peptides containing modified amino acids by the total quantity of peptides containing those particular amino acids (modified and unmodified) and then multiplying the result by 100. This yielded the percentage of modified amino acids at the designated location. Refer to FIG.16. Example 6. Low Skid Silk / Modified Polypeptide Compositions Isolated by Charge and Size Properties Described herein is a novel method to generate compositions of polypeptide that are derived from B. mori silkworm cocoons and comprise of natural and modified DB1 / 147842605.1112 polypeptides. This novel composition is called Low Skid silk / modified polypeptide compositions. The novel production method involves removing sericin through several washing steps with an organic sodium carbonate salt with tightly controlled multi-stage temperature cycles and agitation as the first step in forming natural / modified polypeptide composition. Next the silk is dried to remove remaining water at controlled temperature to maintain polypeptide composition. The silk is then dissolved in high concentration of Lithium salt at 125°C for 6 hours to achieve the compositions of Low Skid silk. The liquid solution is then filtered and purified to remove the Lithium salt leaving only the natural / modified silk compositions in solution with pure water. Low Skid silk / modified polypeptide compositions comprise of populations of silk / modified polypeptides with distinctive properties. Low Skid silk / modified polypeptide composition does not self-assemble at 5 mg / mL. Low Skid silk / modified polypeptide composition comprises of a variety of populations of silk / modified polypeptides; distinct populations were isolated based on charge and size, by fractionating Low Skid silk / modified polypeptides by anion exchange chromatography and size exclusion chromatography. A high-resolution separation of five negatively-charged silk compositions was achieved– AS77, AS78, AS79, AS80, and AS81. These silk compositions differ from one another by their average size, when AS77 is the largest, and AS81 is the smallest. These silk compositions do not self- assemble under conditions that promote self-assembly at 5 mg / mL. The Low Skid silk / modified polypeptide compositions described in this invention are novel compositions of silk and modified polypeptides composed of a variety of silk polypeptide populations, generated by the exclusive treatment method of natural silk produced by B. mori. These silk compositions contain modified amino acid sequences that result from silk processing method and scale. The tight controls over temperature, silk concentration, buffers and salt concentrations, physical agitation, and purification allow for the precise development of silk compositions with a variety of performance criteria. Isolation of these populations by charge and size reveals new characteristics, like high solubility and stability in solution over time in these populations. The purification method allows for the isolation of silk / modified polypeptide compositions that display biological activities and could be used for therapeutic purposes. DB1 / 147842605.1113 Silk is a complex natural biomaterial that has the potential to be utilized in various applications such as the development of implantable medical devices, and the development of soluble polypeptide compositions of medical value. Additionally, it was demonstrated that silk peptides have anti-genotoxic effects. However, silk, in its natural form, is not soluble, and silk polypeptide compositions, without the proper processing, display poor solubility in solution and tend to self-assemble and aggregate over time. The kinetics of this self-assembly is unpredictable, and highly depends on the composition of the silk polypeptides / modified composition. Novel silk / modified polypeptide compositions were produced and the silk / modified polypeptide compositions isolated specific populations within these compositions. The isolation process allows for the control of the properties of the silk compositions and development of products with predictable and desired characteristics. Generation of Low Skid silk / modified polypeptide compositions. Silk is washed to remove sericin at 100°C and 60°C with sodium carbonate and then dried at 60°C. The silk is then dissolved in 9.3M Lithium Bromide at 125°C for 6 hours. This dissolution step controls not only molecular weight but also the polypeptide modifications creating the natural / modified silk compositions. The silk is then filtered to remove undissolved debris and purified using 10 kDa cutoff PES hollow fiber membranes and concentrated using the same process leaving only natural / modified silk composite in solution with pure water. Every unit ops is tightly controlled for temperature, time, concentrations, agitation, and shear. Isolation of Low Skid / modified polypeptide compositions Isolation of the AS77-AS81 silk / modified polypeptide composition component of Low Skid silk / modified polypeptide composition. To isolate AS77-AS81 Low Skid silk / modified polypeptide compositions were fractioned using anion exchange chromatography (Q-Sepharose chromatography), following HiLoad 26 / 600 Superdex 200 pg size exclusion chromatography of the Q- eluate (FIG. 1 and FIG. 2). Prior to chromatography, Tris was added to the silk preparations to a final concentration of 50 mM Tris–HCl, pH=8.0. The silk was centrifuged and filtered before loading to the Q-Sepharose column, to remove any preformed aggregates. The silk compositions were loaded onto the Q-Sepharose column, and the flowthrough fraction was collected. The negatively charged silk compositions were eluted using high salt buffer (50 mM Tris, 500 mM CaCl2). The DB1 / 147842605.1114 eluted fractions were pulled together and are referred to as the Q-elution fraction. The Q-elution was further fractionated by the HiLoad 26 / 600 Superdex 200 pg, where the largest polypeptide compositions were eluted first, and each following fraction had a population of lower molecular weight of silk compositions (FIG.17 and FIG.18A-18B). Low Skid silk preparation solutions have a characteristic yellow hue. The Q-elution fraction has a strong yellow hue, while the flowthrough fraction is transparent, and tends to self-assemble very quickly. The Q-elution silk compositions that are fractionated by size exclusion also had a yellow hue. When silk formulations AS77-AS81 are analyzed with an analytical SEC column (see materials and methods) with HPLC, each of the silk formulations demonstrates a different average Mw, and a different Polydispersity (PDI) value (FIGS. 19A-19B, Table 7). In general, AS77 has the highest Mw (55714 Da), while AS81 has the lowest Mw (28750 Da). The PDI values display a differential change as well. The PDI value of AS77 is relatively low (1.1836), and AS81 is higher (1.3648) (FIG.19A-19B, Table 7). Unfractionated Low Skid silk has an average Mw of ~19500, indicating that most of the peptide population tends to have lower molecular weight than fractions AS77-AS81. The polydispersity of unfractionated Low Skid silk is ~2.2 – significantly higher than the values of fractions AS77-AS81. This indicated that the unfractionated Low Skid silk is composed of a much diverse peptide population compared to fractions AS77-AS81. AS77-AS81 silk compositions demonstrate relative uniformity by dynamic light scattering and show gradual particle size distribution. In dynamic light scattering analysis (Zetasizer Pro, Table 6), AS77-AS81 demonstrated relatively uniform, though broad, peaks where AS77 has the largest Z-average (17.16 nm), then AS78 (15.14 nm), and so on (Table 6), demonstrating the efficiency of the fractionation by size of the Q-elution fraction. Self-Assembly of Low and Mid Skid / modified polypeptide compositions Self-assembly assay and data derived from it. To study the stability of silk / modified peptide compositions in solution, Self-Assembly assays at a concentration of 5 mg / mL were performed. The absorbance at 550nm curves of the self-assembly assays are sigmoid and they can be described as logistic curves. The typical logistic function is: ^^( ^^) =^^ೌ^ Amaxis the maximum density of the gel formed k is the Self-Assembly Rate Factor (SARF) t0.5is the time point at which 50% of the gel has formed e is the exponential equation for the specific curve (see FIG.21A the red dotted lines for a better demonstration of how these factors from the Self-Assembly experiments were calculated) Another parameter introduced to characterize the propensity of silk to form gels is the Self-Assembly Factor (FSAF) which is: 1^^ௌ^ி=^^0.5( ^^ ^^ ^^)∗ ^^^^௫( ^^ ^^ ^^) ∗ 1000 Self-Assembly assays that were performed with the various novel isolated silk polypeptides, these parameters were calculated and used to dissect their properties (FIGS. 21A-21B). Four parameters were focused on, collectively referred to as Self-Assembly kinetic factors; the Self-Assembly Rate Factor (SARF), Amax, t0.5, and the Self-Assembly Factor (SAF) (FIGS.21A-21B). The SARF shows how fast silk self-assembles to form gel after the reaction begins or the gelation nuclei have formed; Amaxshows how dense is the gel that is formed after self-assembly is complete, t0.5 shows how long it takes for the self-assembly reaction to reach the point where gel density is^^ೌ^ଶ and SAF shows the propensity of silk to self-assemble (FIGS.21A-21B). AS77-AS81 silk compositions do not self-assemble. Self-assembly assays revealed that Low Skid silk / modified peptide compositions do not self-assemble under the experimental system conditions (FIG. 22A). No self-assembly occurred after 24 hours, and no self-assembly was detected even 12 days post-assay (FIG.22B). Mid Skid / modified peptide compositions was used as a positive control and shows fast self-assembly kinetics (FIGS.21A-21B). Materials and Methods used for the generation and characterization of AS77- AS81. Anion exchange chromatography of silk. Low Skid silk was provided at a concentration of 60 mg / mL.50 mM Tris, pH=8.0 buffer was added to the Low Skid silk, and the silk was centrifuged at 16000 rpm (rotor JA- DB1 / 147842605.1116 18, Beckman coulter, average of 28100 xg), at 4°C, for 30 min to separate formed aggregates from soluble silk. The supernatant was collected and filtered through a 0.22 µm PES filter. For silk fractionation, Q-Sepharose prepacked columns connected to an AKTA pure 25L or HiPrep Q FF 16 / 1020 mL Column, or HiTrap™ Capto™ Q 1 mL column was used. All buffers used were filtered through a 0.22 μm PES filter and degassed with sonication. Centrifuged and filtered Low Skid silk was loaded on 5 x 5mL HiTrap Q HP columns washed with 10 column volumes of 50 mM Tris pH=8.0, 10 column volumes of 50 mM Tris pH=8.0, 500 mM CaCl2and finally 10 column volumes of 50 mM Tris pH=8.0.170 mL of centrifuged Low Skid silk were loaded on the column with a flow rate of 5 mL / min. The flow-through was collected. The column was washed with 50 mM Tris pH=8.0 until the absorbance at 280nm [A280] got to 100 AU. Bound protein was eluted in one step with 50 mM Tris pH=8.0, 500 mM CaCl2and all fractions with absorbance [A280] >500AU were pooled together. The Q-elution fraction (the eluate) was then used for further fractionation by size exclusion chromatography. Size Exclusion Chromatography of Silk. The Low Skid silk eluate fraction of the Q-Sepharose anion exchange chromatography (Q-elution) was the starting material for size exclusion chromatography. The eluate was loaded onto a HiLoad 26 / 600 Superdex 200 pg gel filtration column for fractionation, using the AKTA Pure 25L system. All buffers used during fractionation were filtered through 0.22 µm PES filter as well and were degassed. The Low Skid silk was loaded on the Superdex 200 gel filtration column, and was run with 50 mM Tris, 200 mM CaCl2, pH=8.0, to fractionate the Q-elution Low Skid silk. The eluted silk compositions were collected in 10 ml fractions. Fractions 6-10 (AS77, AS78, AS79, AS80, AS81) were collected, and have relatively narrow range of molecular weight. The fractions were placed in 3.5 kDa cutoff dialysis bags, and were concentrated by covering the dialysis bags with polyethylene glycol 35000 Da. Then, fractions in the dialysis bags were immersed in 160X volumes of 50 mM Tris pH=8.0 overnight, and then were immersed in a new batch of 160X volume of 50 mM Tris pH=8.0. Samples were kept at 4°C until they were used. Analytical / Protein Characterization methods. Protein concentration determination. DB1 / 147842605.1117 Protein concentration was determined by absorbance at 220nm or 280nm. Solubilized silk preparations were diluted until A280was between 0.1-1. In this range the absorbance correlates linearly with the concentration of silk in the solution and the correlation is 1AU=1mg / mL soluble silk proteins. Final concentrations in the initial silk solution were calculated after adjustment for the dilution used for the absorbance measurement. Analytical Size Exclusion Chromatography. Analytical Size Exclusion Chromatography is performed as described in detail in the document EMED-QCP-SILK1-002. Analysis was performed in a PolySep GFC P-4000 LC Column, 300 mm x 7.8 mm connected to an Agilent 1260 Infinity II HPLC system with an Agilent G7162A RID Refractive Index Detector. The mobile phase used for the analysis was a solution of 0.1M NaCl, 12.5mM Na2HPO4, pH 7 (the pH was adjusted with phosphoric acid and filtered through a 0.2μm PES filter into a clean glass media bottle). 25μL of sample were loaded on the column and the analysis was performed at 25oC with a flow rate of 1 mL / min for 20 min. Calculation of the molecular weight of each sample was done using Agilent Technologies Open LAB CDS ChemStation Edition for LC & LC / MS Systems software Cirrus SEC data collection and molecular weight analysis software. SDS polyacrylamide gel. Low Skid silk fractions were uploaded onto a Mini-Protean TGX precast gel, 4-20%, with a protein marker Trident Prestained Protein Ladder for molecular weight reference. The SDS polyacrylamide gel was stained using ReadyBlue ^ Protein stain gel. Gels were immersed in ReadyBlue ^ solution for 1 h, then destained with DI / RO water. Self-Assembly Assay. The silk Self Assembly Assay (SAF) was performed in 35% v / v 2-propanol and 50mM CH3COONa pH=5. Each reaction was done in a final volume of 200 μL. Total silk protein concentration was 5 mg / mL. First the buffer of 50 mM CH3COONa pH=5.0, 35% v / v 2-propanol was prepared. Then DI / RO water was added so that after the addition of the volume of silk protein required to reach a final concentration of 5 mg / mL the total volume would be 200 μL. The protein was added last and mixed with very gentle pipetting to reduce shearing force. The protein mixtures were placed in wells of DB1 / 147842605.1118 flat-bottom 96-well plates and a layer of 100 μL of Mineral Oil carefully, so as to not create any bubbles. Absorbance was recorded at 550 nm for 24h. Recorded values were exported in Excel files for storage and further analysis. Dynamic Light Scattering analysis of silk compositions. Low Skid silk compositions were diluted to a concentration of 1 mg / mL and filtered with a 0.22 µm PES syringe filter. All measurements were performed with a Malvern Zetasizer Pro Red Label, detection angle of 173˚. The Red Label system operates with a 10 mW He-Ne laser (633 nm). The software used is ZS XPLORER version 3.2.1.11. All measurements were done with 4.2 ml polystyrol / polystyrene transparent cuvettes. samples were measured at 25°C, with 120 sec of equilibration time. The intensity size distributions, autocorrelation, and Z-average were measured. Table 6: Z-average of AS77-AS81 calculated by Dynamic Light Scattering. The Z- average value of each silk / modified polypeptide composition was calculated by the Zetasizer Pro. Shown here are the Z-average values of each silk composition. The abbreviation d. nm refers to the diameter in nanometers.Z-average (d. Low Skid silk / modified nm) Table 7: Molecular weight (Mw) and Polydispersity (PDI) values of silk compositions AS77-AS81. Silk / modified polypeptide compositions AS77, AS78, AS79, AS80, and AS81 were analyzed by size exclusion chromatography (SEC) column with HPLC, and values of molecular weights (Mw) and Polydispersity (PDI) are indicated. Low Skid silk / modified Mw PDI DB1 / 147842605.1119 AS81 28750 1.3648 Low Skid silk 19500 2.2 ns Isolated by Size Properties Described herein is a novel method to generate compositions of polypeptide that are derived from B. mori silkworm cocoons and comprise of natural and modified polypeptides. This novel composition is called Low Skid silk / modified polypeptide compositions. The novel production method involves removing sericin through several washing steps with an organic sodium carbonate salt with tightly controlled multi-stage temperature cycles and agitation as the first step in forming natural / modified polypeptide composition. Next the silk is dried to remove remaining water at controlled temperature to maintain polypeptide composition. The silk is then dissolved in high concentration of Lithium salt at 125˚C for 6 hours to achieve the compositions of Low Skid silk. The liquid solution is then filtered and purified to remove the Lithium salt leaving only the natural / modified silk compositions in solution with pure water. Low Skid silk / modified polypeptide compositions comprise of populations of silk / modified polypeptides with distinctive properties. Low Skid silk / modified polypeptide composition does not self-assemble at 5 mg / mL. Low Skid silk / modified polypeptide composition comprises of a variety of populations of silk / modified polypeptides; here distinct populations were isolated based on size, by fractionating Low Skid silk / modified polypeptides by size exclusion chromatography. A high-resolution separation of five silk compositions – AS82, AS83, AS84, AS85, and AS86 was achieved. These silk compositions differ from one another by their average size, when AS82 is the largest, and AS86 is the smallest. These silk compositions do not self-assemble under conditions that promote self-assembly at 5 mg / mL. In addition to the well-separated silk compositions, lower-molecular-weight silk compositions (AS87, AS88, AS89) were generated that are less well-resolved, but composed of significantly smaller polypeptide populations. These silk compositions self-assemble into a gel within a few days under conditions that promote self-assembly at 5 mg / mL, but not as quickly as Mid Skid silk (starting to self-assemble within 3 h). Low Skid silk / modified polypeptide compositions isolated by size properties. DB1 / 147842605.1120 The Low Skid silk / modified polypeptide compositions described in this invention are novel compositions of silk and modified polypeptides composed of a variety of silk polypeptide populations, generated by the exclusive treatment method of natural silk produced by B. mori. These silk compositions contain modified amino acid sequences that result from the silk processing method and scale. The tight controls over temperature, silk concentration, buffers and salt concentrations, physical agitation, and purification allow us to precisely develop silk compositions with a variety of performance criteria. Isolation of these populations by size reveals different characteristics, like high solubility and stability in solution over time in some populations, and the tendency to self-assemble in others. the purification method allows us to isolate silk / modified polypeptide compositions that display biological activities and could be used for therapeutic purposes. Silk is a complex natural biomaterial that has the potential to be utilized in various applications such as the development of implantable medical devices, and the development of soluble polypeptide compositions of medical value. Additionally, it was demonstrated that silk peptides have anti-genotoxic effects. However, silk, in its natural form, is not soluble, and silk polypeptide compositions, without the proper processing, display poor solubility in solution and tend to self-assemble and aggregate over time. The kinetics of this self-assembly is unpredictable, and highly depends on the composition of the silk polypeptides / modified composition. Novel silk / modified polypeptide compositions were produced and specific populations were isolated within these compositions. The isolation process allows us to control the properties of the silk compositions and develop products with predictable and desired characteristics. Generation of Low Skid silk / modified polypeptide compositions. Silk is washed to remove sericin at 100°C and 60°C with sodium carbonate and then dried at 60°C. The silk is then dissolved in 9.3M Lithium Bromide at 125°C for 6 hours. This dissolution step controls not only molecular weight but also the polypeptide modifications creating the natural / modified silk compositions. The silk is then filtered to remove undissolved debris and purified using 10kDa cutoff PES hollow fiber membranes and concentrated using the same process leaving only natural / modified silk composite in solution with pure water. Every unit ops is tightly controlled for temperature, time, concentrations, agitation, and shear. Isolation of Low Skid / modified polypeptide compositions DB1 / 147842605.1121 Isolation of the AS82-AS89 silk / modified polypeptide composition component of Low Skid silk / modified polypeptide composition. To isolate AS82-AS89 Low Skid silk / modified polypeptide compositions were fractioned using HiLoad 26 / 600 Superdex 200 pg size exclusion chromatography column (FIG. 23 and FIG. 24). Tris was added to the silk preparations to a final concentration of 50 mM Tris–HCl, pH=8.0. The silk was centrifuged and filtered before loading to the HiLoad 26 / 600 Superdex 200 pg column, to remove any preformed aggregates. The silk compositions were fractionated by the HiLoad 26 / 600 Superdex 200 pg, where the largest polypeptide compositions were eluted first, and each following fraction had a population of lower molecular weight of silk compositions (Fig. P). Low Skid silk preparation solutions have a characteristic yellow hue, and the fractionated silk compositions had a yellow hue. When silk formulations AS82-AS89 are analyzed with an analytical SEC column (see materials and methods) with HPLC, each of the silk formulations demonstrates a different average Mw, and a different Polydispersity (PDI) value (FIG.24, Table 9). In general, AS82 has the highest Mw (51936 Da), while AS89 has the lowest Mw (6826 Da). The PDI values display a differential change as well. The PDI value of AS82 is relatively low (1.1738), and AS89 is higher (1.3544) (FIGS.25A- 25B, Table 9). AS82-AS86 silk compositions demonstrate relative uniformity by dynamic light scattering, while AS87-AS89 silk compositions contain multiple peptide populations sizes. In dynamic light scattering analysis (Zetasizer Pro, FIGS. 28A-28C, Table 8), AS82- AS86 demonstrated relatively uniform, though broad, peaks where AS82 has the largest Z-average (18.174 nm), then AS83 (15.659 nm), and so on (Table 9). AS87, AS88, and AS89 are of lower molecular weight, and are eluted later during the chromatography, where the resolution of the Superdex 200 is not optimal and cannot resolve the peptide populations very well (the column resolution is reduced for proteins smaller than average size of ~44 kDa), as can be observed by SDS gel electrophoresis in FIG. 26 (fraction 11 and on). Dynamic light scattering shows two peaks for these fractions, indicating the presence of several populations (FIG.28A). Self-Assembly of Low and Mid Skid / modified polypeptide compositions Self-Assembly assay and data derived from it. DB1 / 147842605.1122 To study the stability of silk / modified peptide compositions in solution Self-Assembly assays were performed at a concentration of 5 mg / mL. The absorbance at 550nm curves of the self-assembly assays are sigmoid and they can be described as logistic curves. The typical logistic function is: ^^( ^^) =^^ೌ^^ା^షೖ(^ష^బ.ఱ) density of the gel formed k is the Self-Assembly Rate Factor (SARF) t0.5is the time point at which 50% of the gel has formed e is the exponential equation for the specific curve (see FIG.27A the red dotted lines for a better demonstration of how these factors from the Self-Assembly experiments were calculated) Another parameter that was introduced to characterize the propensity of silk to form gels is the Self-Assembly Factor (FSAF) which is: 1^^ௌ^ி=^^ ^^∗ ^^^^௫( ^^ ^^ ^^) ∗ 1000 Using the experimental data from the Self-Assembly assays that were performed with the various novel isolated silk polypeptides, these parameters were calculated and used to dissect their properties (FIGS. 27A-27B). Four parameters were focused on, collectively referred to as Self-Assembly kinetic factors; the Self-Assembly Rate Factor (SARF), Amax, t0.5, and the Self-Assembly Factor (SAF) (FIGS.27A-27B). The SARF silk self-assembles to form gel after the reaction begins or the gelation nuclei have formed; Amax shows how dense is the gel that is formed after self-assembly is complete, t0.5 shows how long it takes for the self-assembly reaction to reach the point where gel density is^^ೌ^ଶ and SAF shows the propensity of silk to self-assemble (FIGS.27A-27B). AS82-AS86 silk compositions do not self-assemble. Self-assembly assays revealed that Low Skid silk / modified peptide compositions do not self-assemble under the experimental system conditions (FIG..27A). No self-assembly DB1 / 147842605.1123 occurred after 24 hours, and no self-assembly was detected even 18 days post-assay (FIG.27B). Mid Skid / modified peptide compositions was used as a positive control and shows fast self-assembly kinetics (FIGS.27A-27B). AS87-AS89 silk compositions self-assemble within few days. Self-assembly assays as described before, revealed that AS87-AS89 do not self- assemble within 24 hours (FIG. 27A). However, if left for an extra 4-5 days, self- assembly occurs in these silk / modified polypeptide compositions (FIG. 27B). Mid Skid / modified peptide compositions was used as a positive control and shows fast self- assembly kinetics (FIGS.27A- 27B). Materials and Methods used for the generation and characterization of AS82- AS89. Size Exclusion Chromatography of Silk. The starting material, Low Skid silk at a concentration of 60 mg / mL, was provided by the manufacturing team. The Low Skid silk was transferred to 50 mM Tris, pH=8.0 buffer, and centrifuged at 16000 rpm, at 4°C, for 30 min to separate formed aggregates from soluble silk. The supernatant was collected and filtered through a 0.22 µm PES filter. Then, the silk was loaded onto a HiLoad 26 / 600 Superdex 200 pg gel filtration column for fractionation, using the AKTA Pure 25L system. All buffers used during fractionation were filtered through 0.22 µm PES filter as well and were degassed. The Low Skid silk was loaded on the Superdex 200 gel filtration column, and was run with 50 mM Tris, 200 mM CaCl2, pH=8, to fractionate the Low Skid silk. The eluted silk compositions were collected in 10 ml fractions. Fractions 6-10 (AS82, AS83, AS84, AS85, AS86) were collected, and have relatively narrow range of molecular weight, while fractions 18-20 (AS87, AS88, AS89) have a broader molecular weight range, since these molecular sizes are outside of the HiLoad 26 / 600 Superdex 200 pg separation range. The fractions were placed in 3.5 kDa cutoff dialysis bags, and were concentrated by covering the dialysis bags with polyethylene glycol 35000 Da. Then, fractions in the dialysis bags were immersed in 160X volumes of 50 mM Tris pH=8.0 overnight, and then were immersed in a new batch of 160X volume of 50 mM Tris pH=8.0. Samples were kept at 4°C until they were used. Analytical / Protein Characterization methods. Protein concentration determination. DB1 / 147842605.1124 Protein concentration was determined by absorbance at 220nm or 280nm. Solubilized silk preparations were diluted until A280was between 0.1-1. In this range the absorbance correlates linearly with the concentration of silk in the solution and the correlation is 1AU=1mg / mL soluble silk proteins. Final concentrations in the initial silk solution were calculated after adjustment for the dilution used for the absorbance measurement. Analytical Size Exclusion Chromatography. Analytical Size Exclusion Chromatography is performed as described in detail in the document EMED-QCP-SILK1-002. Analysis was performed in a PolySep GFC P-4000 LC Column, 300 mm x 7.8 mm connected to an Agilent 1260 Infinity II HPLC system with an Agilent G7162A RID Refractive Index Detector. The mobile phase used for the analysis was a solution of 0.1M NaCl, 12.5mM Na2HPO4, pH=7 (the pH was adjusted with phosphoric acid and filtered through a 0.2μm PES filter into a clean glass media bottle). 25μL of sample were loaded on the column and the analysis was performed at 25°C with a flow rate of 1 mL / min for 20 min. Calculation of the molecular weight of each sample was done using Agilent Technologies Open LAB CDS ChemStation Edition for LC & LC / MS Systems software Cirrus SEC data collection and molecular weight analysis software. SDS polyacrylamide gel. Low Skid silk fractions were uploaded onto a Mini-Protean TGX precast gel, 4-20%, with a protein marker Trident Prestained Protein Ladder for molecular weight reference. The SDS polyacrylamide gel was stained using ReadyBlue ^ Protein stain gel. Gels were immersed in ReadyBlue ^ solution for 1 h, then destained with DI / RO water. Self-Assembly Assay. The silk Self Assembly Assay (SAF) was performed in 35% v / v 2-propanol and 50mM CH3COONa pH=5. Each reaction was done in a final volume of 200μL. Total silk protein concentration was 5mg / mL. First the buffer of 50mM CH3COONa pH=5, 35% v / v 2-propanol was prepared. Then DI / RO water was added so that after the addition of the volume of silk protein required to reach a final concentration of 5mg / mL the total volume would be 200μL. The protein was added last and mixed with very gentle pipetting to reduce shearing force. The protein mixtures were placed in wells of flat- DB1 / 147842605.1125 bottom 96-well plates and a layer of 100μL of Mineral Oil carefully so as to not create any bubbles. Absorbance was recorded at 550nm for 24h. Dynamic Light Scattering analysis of silk compositions. Low Skid silk compositions were diluted to a concentration of 1 mg / mL and filtered with a 0.22 µm PES syringe filter. All measurements were performed with a Malvern Zetasizer Pro Red Label, detection angle of 173˚. The Red Label system operates with a 10 mW He-Ne laser (633 nm). The software used is ZS XPLORER version 3.2.1.11. All measurements were done with 4.2 mL polystyrol / polystyrene transparent cuvettes. samples were measured at 25˚C, with 120 sec of equilibration time. The intensity size distributions, autocorrelation, and Z-average were measured. Table 8: Z-average of AS82-AS89 calculated by Dynamic Light Scattering. The Z- average value of each silk / modified polypeptide composition was calculated by the Zetasizer Pro. Shown here are the Z-average values of each silk composition. Low Skid silk / modified polypeptide Z-average (d. composition nm) Table 9: Molecular weight (Mw) and Polydispersity (PDI) values of silk compositions AS82-AS89. Silk / modified polypeptide compositions AS82, AS83, AS84, AS85, AS86, AS87, AS88, and AS89 were analyzed by size exclusion chromatography (SEC) column with HPLC, and values of molecular weights (Mw) and Polydispersity (PDI) are indicated. Low Skid silk / modified polypeptide Mw PDI DB1 / 147842605.1126 AS86 23574 1.235 AS87 8668 1.425 arge, hydrophobicity levels, and size properties Described herein is a novel method to generate compositions of polypeptide that are derived from B. mori silkworm cocoons and comprise of natural and modified polypeptides. This novel composition is called Low Skid silk / modified polypeptide compositions. The novel production method involves removing sericin through several washing steps with an organic sodium carbonate salt with tightly controlled multi-stage temperature cycles and agitation as the first step in forming natural / modified polypeptide composition. Next the silk is dried to remove remaining water at controlled temperature to maintain polypeptide composition. The silk is then dissolved in high concentration of Lithium salt at 125˚C for 6 hours to achieve the compositions of Low Skid silk. The liquid solution is then filtered and purified to remove the Lithium salt leaving only the natural / modified silk compositions in solution with pure water. Low Skid silk / modified polypeptide compositions comprise of populations of silk / modified polypeptides with distinctive properties. Low Skid silk / modified polypeptide composition does not self-assemble at 5 mg / mL. Low Skid silk / modified polypeptide composition comprises of a variety of populations of silk / modified polypeptides; here it was sought to isolate distinct populations based on charge, hydrophobicity, and size, by fractionating Low Skid silk / modified polypeptides by anion exchange chromatography, followed by hydrophobic interaction chromatography and size exclusion chromatography. A high-resolution separation of ten distinct Low Skid silk / modified polypeptides compositions was achieved: five are negatively-charged silk compositions that display hydrophobicity characteristics as well – AS90, AS91, AS92, AS93, and AS94. These silk compositions differ from one another by their average size, when AS90 is the largest, and AS94 is the smallest. These silk compositions do not self-assemble under conditions that promote self-assembly at 5 mg / mL. DB1 / 147842605.1127 Additional five compositions are negatively charged silk compositions as well, that are less hydrophobic compared to AS90-AS94, and have relatively lower molecular weights (AS95, AS96, AS97, AS98, AS99, AS100). These silk compositions differ from one another by their average size, when AS95 is the largest, and AS100 is the smallest. These silk compositions may have the tendency to aggregate in solution, as can be demonstrated by dynamic light scattering and loss of material after filtration with 0.2 µm PES filter. The Low Skid silk / modified polypeptide compositions described in this invention are novel compositions of silk and modified polypeptides composed of a variety of silk polypeptide populations, generated by the exclusive treatment method of natural silk produced by B. mori. These silk compositions contain modified amino acid sequences that result from the silk processing method and scale. The tight controls over temperature, silk concentration, buffers and salt concentrations, physical agitation, and purification allow us to precisely develop silk compositions with a variety of performance criteria. Isolation of these populations by charge, hydrophobicity, and size reveals new characteristics, like high solubility and stability in solution over time in some populations, and the tendency to aggregate in others. the purification method allows us to isolate silk / modified polypeptide compositions that display biological activities and could be used for therapeutic purposes. Silk is a complex natural biomaterial that has the potential to be utilized in various applications such as the development of implantable medical devices, and the development of soluble polypeptide compositions of medical value. Additionally, it was demonstrated that silk peptides have anti-genotoxic effects However, silk, in its natural form, is not soluble, and silk polypeptide compositions, without the proper processing, display poor solubility in solution and tend to self-assemble and aggregate over time. The kinetics of thi...

Claims

CLAIMS:

1. A method of treatment or prevention of a disorder, disease, or condition in a subject in need thereof, the method comprising administering to the subject a composition comprising fibroin fragments, wherein the fibroin fragments comprise a plurality of modified fibroin fragments.

2. The method of claim 1, wherein the disease, disorder or condition is selected from Atopic Dermatitis (Eczema), Psoriasis (e.g., plaque psoriasis), Contact Dermatitis, rosacea, acne (e.g., cystic acne), Ichthyosis (e.g., ichthyosis vulgaris), inflammation, Netherton Syndrome (a genetic disorder that lead to chronic skin inflammation and increased susceptibility to an infection), Xerosis (Dry Skin), Aging Skin, impaired wound healing, Diabetic Dermopathy, Pruritus, Scleroderma, Multiple Sclerosis (MS), Bacterial and fungal Infection, abnormal scarring condition, melanoma, dysbiosis, autoimmune condition like lupus, Systemic Lupus Erythematosus, and rheumatoid arthritis.

3. The method of claim 1, wherein the disorder, disease, or condition is an inflammatory disease, disorder or condition selected from Rheumatoid Arthritis, Inflammatory Bowel Disease, Systemic Lupus Erythematosus, Multiple Sclerosis (MS), Psoriasis, Asthma, allergic rhinitis, asthma, food allergy, and another autoimmune condition.

4. The method of claim 1, wherein the disease, disorder or condition is selected from inflammatory bowel disease (IBD), Intestinal Permeability, Crohn's disease, ulcerative colitis, celiac disease, irritable bowel syndrome (IBS), NASH, cirrhosis, metabolic disorders, and another disease, a disorder or condition involving regulation of a gut epithelial cell.

5. The method of claim 1, wherein the disease, disorder or condition is a neurodegenerative condition selected from Alzheimer’s Disease (AD), Multiple Sclerosis (MS), Parkinson’s Disease (PD), and Amyotrophic Lateral Sclerosis (ALS). DB1 / 147842605.13526. The method of claim 1, wherein the disease, disorder or condition is a metabolic condition selected from obesity and type 2 Diabetes, and non-alcoholic fatty liver disease (NAFLD).

7. The method of claim 1, wherein the disease, disorder or condition is a cancer.

8. The method of claim 4, wherein the disease, disorder or condition is associated with dysregulation in a gut barrier and / or in a tight junction of the gut.

9. The method of any one of the preceding claims, wherein a fibroin fragment interacts with lipoteichoic acid, lipomannan, a TLR-2 receptor, or a protein kinase.

10. The method of claim 9, wherein the protein kinase is a Tyrosine-protein kinase.

11. The method of any one of the preceding claims, wherein a fibroin fragment binds to a protein disulfide isomerase (PDI), a CD44 receptor, Annexin A2, Keratin 5, Keratin 1, or Keratin 10.

12. The method of any one of the preceding claims, wherein a fibroin fragment binds to a CD44 receptor.

13. The method of any one of the preceding claims, wherein the disease, disorder, or condition is alleviated by decreasing the secretion of TNF-α and IL-6, and / or increasing secretion of IL-10.

14. The method of any one of the preceding claims, wherein the disease, disorder, or condition is alleviated by modulating Annexin A2’s role in tumor growth, immune function, neuronal protection, and / or metabolic processes.

15. The method of any one of the preceding claims, wherein the disorder, disease, or condition is alleviated by stimulating or modulating a skin barrier-specific protein in a subject in need thereof. DB1 / 147842605.135316. The method of claim 15, wherein the skin barrier-specific protein is differentially regulated.

17. The method of claim 15 or 16, wherein the skin barrier-specific protein comprises at least one of desmoplakin (DSP), cystatin A (CSTA), tumor-associated calcium signal transducer 2 (TACSTD2), biglycan (BGN), decorin (DCN) and / or epiplakin 1 (EPPK1).

18. The method of any one of claims 15 to 17, wherein at least one of desmoplakin (DSP), cystatin A (CSTA) and / or tumor-associated calcium signal transducer 2 (TACSTD2) is upregulated post-administration.

19. The method of any one of claims 15 to 17, wherein at least one of biglycan (BGN), decorin (DCN) and / or epiplakin 1 (EPPK1) is downregulated post- administration.

20. The method of claim 15 or 16, wherein at least one of the skin barrier-specific protein is a tight junction protein.

21. The method of claim 20, wherein a fibroin fragment binds to a skin epithelial cell and / or induces upregulation of the tight junction protein.

22. The method of claim 20 or 21, wherein the tight junction protein is Claudin-1, occludin, or Zo1.

23. The method of any one of claims 20-22, wherein the tight junction protein is Claudin-1 expressing in a human epidermal keratinocyte.

24. The method of claim 22 or 23, wherein a claudin-1 level is promoted, increased, or restored post-administration in the epidermal keratinocyte.

25. The method of claim 23, or 24, the epidermal keratinocyte is an h-TERT immortalized keratinocyte. DB1 / 147842605.135426. The method of claim 25, wherein the epidermal keratinocyte is a primary human keratinocyte.

27. The method of any one of claims 1-26, wherein a fibroin fragment promotes a growth of a normal skin microbiome and a probiotic bacteria by interacting with a receptor on a probiotic bacteria surface.

28. The method of claim 27, wherein the probiotic bacteria is selected from Micrococcus luteus, Lactiplantibacillus plantarum, and Lacticaseibacillus rhamnosus.

29. The method of any one of the preceding claims, wherein administering the composition improves the function of a skin keratinocyte and a fibroblast.

30. The method of any one of the preceding claims, wherein administering the composition promotes skin barrier function, regulates immune responses, and / or confers pathogen bacteria colonization resistance.

31. The method of any one of the preceding claims, wherein the fibroin fragment penetrates an intact skin barrier and binds to a dermal fibroblast.

32. The method of any one of the preceding claims, wherein administering the composition induces de novo collagen synthesis, secretion and / or increases extracellular matrix deposition.

33. The method of any one of the preceding claims, wherein administering the composition induces secretion of pro-Col1A1, Col3A, and / or ɑ-SMA.

34. The method of any one of the preceding claims, wherein the fibroin fragment accelerates skin barrier regeneration by promoting expression of the tight junction protein. DB1 / 147842605.135535. The method of any one of the preceding claims, the fibroin fragment is a keratinocyte differentiation factor (KDF) polypeptide.

36. The method of claim 35, wherein the KDF polypeptide enhances keratinocyte differentiation and / or Filaggrin maturation.

37. The method of claim 35, wherein the KDF polypeptide increases expression and maturation of Involucrin and / or Filaggrin A.

38. The method of claim 35, wherein the tight junction protein is selected from Claudin-1 and Occludin.

39. The method of claim 35, wherein the KDF polypeptide binds to a corneal keratin selected from Keratin 1 and Keratin 10.

40. The method of claim 35, wherein the KDF polypeptide induces a switch from a basally-expressed keratin (e.g. K5, K14) to a suprabasally-expressed keratin (e.g. K1, K10).

41. The method of claim 35, wherein the KDF polypeptide enters the skin and binds selectively to the CD44 receptor on a stratum basale cell.

42. The method of claim 35, wherein the KDF polypeptide binds to an undifferentiated keratinocyte in the skin and accelerates keratinocyte differentiation to accelerate skin barrier regeneration.

43. The method of claim 35, wherein the composition maintains skin extracellular matrix (ECM) homeostasis.

44. The method of any one of the preceding claims, wherein the subject in need experiences reduced erythema post-administration, decreased transepidermal water loss post-administration, a reduced eczema lesion count post-administration, reduced edema post-administration, reduced rhytids post-administration, increased skin DB1 / 147842605.1356hydration post-administration, increased skin firmness post-administration, a reduced sign of skin inflammation post-administration, and / or a reduced sign of aging skin post-administration.

45. The method of any one of the preceding claims, wherein the composition is administered in combination with vitamin C.

46. The method of any one of the preceding claims, wherein administering the composition in combination with vitamin C synergistically increases pro-Col1A1 secretion.

47. The method of any one of the preceding claims, wherein the composition is administered parenterally.

48. The method of any one of the preceding claims, wherein the composition is formulated as a topical composition.

49. The method of any one of the preceding claims, wherein the composition comprises a population of neutral fibroin fragments, a population of positively charged fibroin fragments, or a population of negatively charged fibroin fragments.

50. The method of any one of the preceding claims, wherein the silk fibroin fragments have a weight average molecular weight from about 1 kDa to about 250 kDa.

51. The method of any one of the preceding claims, wherein the composition comprises a fibroin fragment subpopulation having a weight average molecular weight selected from between about 5 kDa to about 10 kDa, between about 10 kDa to about 40 kDa, between about 40 kDa to about 70 kDa, between about 70 kDa to about 100 kDa, between about 100 kDa to about 130 kDa, between about 130 kDa to about 150 kDa, between about 150 kDa to about 180 kDa, between about 180 kDa to about 210 kDa, or between about 210 kDa to about 240 kDa. DB1 / 147842605.135752. The method of any one of claims 1-50, wherein the composition comprises a fibroin fragment subpopulation having a weight average molecular weight selected from between about 20 kDa to about 50 kDa, between about 50 kDa to about 80 kDa, between about 80 kDa to about 110 kDa, between about 110 kDa to about 140 kDa, between about 140 kDa to about 170 kDa, between about 170 kDa to about 200 kDa, between about 200 kDa to about 230 kDa, or between about 230 kDa to about 250 kDa.

53. The method of any one of the preceding claims, wherein the composition comprises a fibroin fragment subpopulation having a polydispersity selected from between 1 to about 3.

54. The method of any one of the preceding claims, wherein the composition comprises a fibroin fragment subpopulation having an isoelectric point selected from between about 4.4 to about 9.

6.

55. The method of any one of claims 1 to 54, wherein the composition comprises a fibroin fragment subpopulation having a self assembly rate factor selected from between 0 to about 5.

56. The method of any one of claims 1 to 55, wherein the composition comprises a fibroin fragment subpopulation having a self assembly rate factor selected from between about 0.6 to about 4.

57. The method of any one of claims 1 to 56, wherein the composition comprises a fibroin fragment subpopulation each having a self assembly factor selected from between about 0.5 to about 0.

9.

58. The method of any one of claims 1 to 54, wherein the composition comprises a fibroin fragment subpopulation having a self assembly rate factor selected from between about 5 to about 11. DB1 / 147842605.135859. The method of any one of the preceding claims, wherein the composition comprises a fibroin fragment subpopulation having an Amaxselected from between 0 to about 0.

7.

60. The method of any one of the preceding claims, wherein the composition comprises a fibroin fragment subpopulation having an Amaxselected from between about 0.5 to about 0.

8.

61. The method of any one of the preceding claims, wherein the composition comprises a fibroin fragment subpopulation having a t0.5(min) selected from between 0 to about 1500.

62. The method of any one of the preceding claims, wherein the composition comprises a fibroin fragment subpopulation having a t0.5(min) selected from between 0 to about 1000.

63. The method of any one of the preceding claims, wherein the modified fibroin fragments comprise one or more amino acid residue modifications selected from an asparagine to aspartic acid modification, a glutamine to glutamic acid modification, and a methionine to methionine oxide modification.

64. The method of claim 63, wherein a plurality of modified fibroin fragments comprise one modification.

65. The method of claim 63, wherein a plurality of modified fibroin fragments comprise two modifications.

66. The method of claim 63, wherein a plurality of modified fibroin fragments comprise three modifications.

67. The method of any one of claims 63 to 66, wherein the asparagine to aspartic acid modification is at one or more positions selected from N23, N28, N108, N118, DB1 / 147842605.1359N136, N186, N200, N204, N240, N248, N68, N70, N77, N5262, N93, N132, N149, N172, N174, N202, N105, N4191.

68. The method of any one of claims 63 to 66, wherein the glutamine to glutamic acid modification is at one or more positions selected from Q24, Q149, Q202, Q58, Q139, Q275, Q5216, Q255, and Q125.

69. The method of any one of claims 63 to 66, wherein the methionine to methionine oxide modification is at the M64 position.

70. The method of any one of claims 63 to 69, wherein a % modification is defined as (number of modified fibroin fragments having a modification at a specific position divided by the total number of fibroin fragments which includes the specific position, modified or unmodified) x 100.

71. The method of any one of claims 63 to 70, wherein each modification is independently ranging in the composition between about 1% to about 99%.

72. The method of any one of the preceding claims, wherein the composition further comprises a pharmaceutically acceptable carrier.

73. The method of claim 72, wherein the pharmaceutically acceptable carrier comprises or is formulated as one or more of a cosmeceutical, a suspension, an emulsion, a powder, a solution, a dispersion, or an elixir.

74. The method of claim 72, wherein the pharmaceutically acceptable carrier comprises or is formulated as one or more of a gel, a jelly, a cream, a lotion, a foam, a slurry, an ointment, an oil, a paste, a suppository, a spray, a semisolid composition, a solid composition, a stick, or a mousse.

75. The method of claim 72, wherein the pharmaceutically acceptable carrier comprises one or more of aliphatic oil, a fatty alcohol, a fatty acid, a glyceride, an acylglycerol, and a phospholipid. DB1 / 147842605.136076. The method of claim 72, wherein the pharmaceutically acceptable carrier comprises one or more of a monoglyceride, a diglyceride, or a triglyceride.

77. The method of claim 72, wherein the pharmaceutically acceptable carrier comprises an aqueous phase.

78. The method of claim 72, wherein the pharmaceutically acceptable carrier comprises an oil-in-water emulsion or a water-in-oil emulsion.

79. The method of claim 72, wherein the pharmaceutically acceptable carrier comprises one or more of a hydrocarbon oil, a fatty acid, a fatty oil, a fatty acid ester, or a cationic quaternary ammonium salt.

80. A dual syringe kit comprising: a first syringe including the composition of any one of claims 1-79 comprising fibroin fragments; and a second syringe including a silk-hyaluronic acid hydrogel.

81. The dual syringe kit of claim 80, wherein the first syringe comprises about 0.1 mL, about 0.2 mL, about 0.3 mL, about 0.4 mL, or about 0.5 mL of the composition.

82. The dual syringe kit of claim 80 or claim 81, wherein the firoin fragments are formulated in an aqueous solution.

83. The dual syringe kit of claim 80 or claim 81, wherein the firoin fragments are formulated in a gel composition.

84. The dual syringe kit of any one of claims 80-83, wherein the second syringe comprises about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, about 1.0 mL, about 1.2 mL, about 1.3 mL, about 1.4 mL, or about 6.5 mL of the silk- hyaluronic acid hydrogel. DB1 / 147842605.136185. The dual syringe kit of any one of claims 80-84, wherein the silk-hyaluronic acid hydrogel is crosslinked.

86. The dual syringe kit of any one of claims 80-85, wherein the composition and the silk-hyaluronic acid hydrogel are mixed together to form an admixture before being applied to a skin of the subject.

87. The dual syringe kit of claim 86, wherein the admixture is applied to the skin of the subject using a derma roller.

88. The dual syringe kit of claim 86, wherein the admixture is applied to the skin of the subject using a microchanneling technique.

89. The dual syringe kit of claim 86, wherein the admixture is applied to the skin of the subject using fractional microneedle radiofrequency (RF).

90. The dual syringe kit of claim 86, wherein the admixture is applied to the subject using platelet-rich plasma (PRP) therapy.

91. The method of claim 1, comprising administering the composition in the admixture of any one of claims 86 to 90 to the subject.

92. The method of claim 91, wherein the subject in need experiences increased stimulation of collagen production post-administration, improved skin hydration post- administration, improved skin texture and elasticity post-administration, a reduction in skin redness post-administration, and / or a reduction in inflammation post- administration.

93. A method for identifying a protein, comprising employing Far Western Blot, SDS-polyacrylamide gel electrophoresis (SDS-PAGE), and / or LC / MS analysis, wherein the fibroin fragment of any one of claims 1-92 binds to the protein. DB1 / 147842605.136294. The method of claim 93, wherein the fibroin fragment is a polypeptide composition derived from B. mori silk.

95. The method of claim 92 or 93, wherein the protein is in a human tissue.

96. The method of claim 94, wherein the human tissue is skin.

97. The method of any one of claims 93-96, wherein the protein in the human tissue is Keratin Type II Cytoskeletal 1 (KRT1), or Keratin type I cytoskeletal 10 (KRT10). DB1 / 147842605.1363

Images