Multilayered products, methods of making same, and uses thereof

Abstract

Multilayer products and methods of making and using same. In various examples, a multilayer product is a graft, such as, for example, a tissue graft, a vascular graft, or the like, or a scaffold, or the like. In various examples, a product comprises an inner layer (e.g., a core or the like) and an outer layer (e.g., a sheath or the like) disposed on at least a portion of an outer surface of the inner layer. In various examples, an outer layer (e.g., an outer layer comprising one or more layer(s)) is formed by electrospinning or the like. In various examples, at least two of the layers of an outer layer are structurally and / or compositionally different) In various examples, a multilayer product is an arteriovenous graft, which may be a compliant arteriovenous graft, or the like. In various examples, an arteriovenous graft is used in a hemodialysis method.

Description

MULTILAYERED PRODUCTS, METHODS OF MAKING SAME, AND USES THEREOFCROSS REFERENCE TO RELATED APPLICATIONS[0001 | This application claims the benefit of U.S. Provisional Application No. 63 / 460,733, filed April 20, 2023; the contents of the above-identified application are hereby fully incorporated herein by reference in their entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0002] This invention was made with government support under grant number HL159427-01 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE DISCLOSURE

[0003] Vascular grafts started with Dacron® in the late 1950s. Studies on classic vascular grafts (Dacron® and ePTFE) suggest that patients would remodel synthetic grafts with their own cells. Most of the host cells in remodeled Dacron and ePTFE grafts are fibroblasts. Host remodeling is largely fibrotic with small amount of host tissue in the interstices of the Dacron graft and occasional partial endothelialization of the lumen. Therefore, existing synthetic vascular grafts are challenged by limited cell infiltration and fibrosis. This pathological remodeling does not improve its mechanical properties and contributes to thrombogenicity. The human body is in a dynamic steady state with constant production and degradation of molecules. Even the remarkably stable extracellular protein, elastin, can be degraded by matrix metalloproteases. The human body makes a few non-degradable tissues, but they grow outward, like hairs, fingernails, and toenails. When growing inwards, these non-degradable structure causes inflammation. Thus, philosophically, it is believed these non-degradable grafts result in a dysfunctional healing process rather than harnessing it.

[0004] A desirable application for vascular grafts is hemodialysis. Dialysis is the only treatment option for over 97% of the end-stage renal disease (ESRD) patients who cannot get a transplant. Approximately 90% of these patients are on hemodialysis. Hemodialysis requires a high flow filtration system. Therefore, hemocompatible material is desirable. When an implanted self-contained artificial kidney becomes a reality, then a relatively low flow system will be feasible. However, it will place even higher requirement on hemocompatibility and overallbiocompatibility. Until such a device is available, addressing critical deficiencies of hemodialysis will impact the care of ESRD patients.|0005| Vascular access for hemodialysis, using either an arteriovenous (AV) fistula or AV graft, is often regarded as the Achilles’s heel because both access strategies have inherent deficiencies. The AV fistula is the gold standard dialysis access and national guidelines on “fistula first” maximize the number of patients who can dialyze through AV fistulae. However, approximately 39% of AV fistulas fail to mature. For matured AV fistula, -40% need interventions to maintain sufficient intra-access blood flow and 29% are abandoned within a year. A fistula is an “abnormal connection between vessels or organs”. In the context of dialysis, connecting an artery directly to a vein induces a huge spike in pressure and turbulent flow, deforming the outflow vein and inflaming its cells. This mechanical overload drives the vein to thicken and adopt arterial like properties to satisfy the newly founded over-pressurized environment. This maturation process is very successful in the setting of a healthy vein. A significant limitation in AV fistula creation is the availability of suitable veins. Because patients with ESRD often have numerous comorbidities and are elderly, the arm veins of these patients are often scarred from numerous prior punctures for blood draws and intravenous catheters. While AV fistulae are superior dialysis accesses, a large fraction of the ESRD population suffer from poor venous anatomy. The placement of AV fistula in the setting of poor veins results in multiple reinterventions and abandoned accesses and this creates a huge financial and emotional burden on patients and increases costs for the healthcare system.

[0006] In the setting of poor veins, AV grafts are placed. The primary patency rate of grafts are 66% at one year, dropping to 40%, 27% and 18% after two, three and five years respectively. Current grafts are susceptible to stenosis, neointimal hyperplasia, rejection, and infection. AV grafts have two source materials: synthetic polymer and blood vessels derived from human or bovine sources. They face even more challenges than the fistula.

[0007] Most synthetic grafts used for AV access creation are made with expanded polytetrafluoroethylene (ePTFE). The elastic modulus of PTFE is approximately 500 MPa depending on preparation. The moduli of veins and arteries vary depending on pressure, but the general range is approximately 15 kPa to 3 MPa, 33,000 to 160 times softer than PTFE. The difference in stiffness between graft and vein is much larger than that between artery and vein. Moreover, synthetic AV grafts are thick and tough to handle repeated cannulation. On the otherhand, veins are thin and soft. The difference in thickness compounds the already stiff graft and further increases the compliance mismatch. Endothelial coverage on ePTFE is very limited. The three-fold challenge of huge compliance mismatch, thrombogenicity and turbulent flow leads to graft failure. In grafts derived from preserved human vessels or fixed decellularized animal vessels, the mismatch of mechanical properties of artery and vein persists: the graft can approximate one compliance or the other, but not both. Further limitations of allografts include poor long-term patency and allosensitization that can impact the patient’s ability to receive a renal transplant. This same immune response can also result in graft inflammation and scarring over time. The xenografts are decellularized and do not have the same immune sensitization but have been shown to have poor primary patency (30% at 1 year), worse than that seen with PTFE (43% at 1 year), and similar infection rates. It only outperforms PTFE in secondary patency.

[0008] When AV fistulae mature, their long-term patency is desirable. However, up to 25- 40% never mature due to poor venous anatomy or poor arterial flows and a significant number of patients are not candidates due to inadequate vein conduit. AV grafts have a lower immediate failure rate but long-term patency is inferior and require multiple interventions to maintain patency due predominantly to the thrombogenicity of the graft material and the compliance mismatch at the venous anastomoses.SUMMARY OF THE DISCLOSURE

[0009] The present disclosure provides, inter alia, products, such as, for example, multilayered grafts and the like. The present disclosure also provides systems for and methods of making products, such as, for example, multilayered grafts and the like.

[0010] In an aspect, the present disclosure provides methods of making products. In various examples, a method comprises electrowriting methods. In various examples, using one or more particular component s), condition(s), system configuration s), or the like, or any combination thereof the methods provide fibrous products having desirable fiber fusion and / or fiber stacking. In various examples, a method is carried out using a system described herein.

[0011] In various examples, a method of making product (such as, for example, a solution electrowritten fibrous product or the like) comprises: ejecting one or more fluid stream(s) of one or more fluid stock(s) from one or more nozzle(s) of a solution electrowriting system (e.g., a solution electrowriting system comprising: the one or more nozzle(s); a material supply system comprising one or more reservoir(s) fluidically coupled to the nozzle(s) and configured to supplyone or more fluid stock(s) to the nozzle(s) thereby ejecting one or more jet stream(s) of the fluid stock(s) from the nozzle(s); a collector system configured to collect one or more fiber(s) formed by the jet stream(s) ejected from the nozzle(s); and optionally, one or more power source(s) configured to provide one or more electric potential(s) to each of the nozzle(s) and, optionally, to the collector system, thereby providing one or more electric potential difference(s) between the collector system and each of the nozzle(s); where each fluid stock comprises a solution comprising at least one first solvent and, optionally, at least one second solvent, and one or more material(s) configured to form at least a portion of a fiber upon ejection of the jet stream(s) of the fluid stock(s) from the nozzle(s), wherein the material(s) is / are dissolvable in at least one of the solvent(s) to form a solution, or the like) to form a plurality of fiber(s); collecting the plurality of fiber with a collector system to form a fibrous product comprising the plurality of fiber arranged in a predetermined pattern disposed on at least a portion of the exterior surfaces of a layer comprising one or more porous elastomer(s); and releasing the fibrous product from the collector system. In various examples, a desired fiber fusion and / or a desired fiber stacking is observed in the fibrous product. In various examples, the ejecting and collecting are repeated a desired number of times to form two or more layers. In various example, a method further comprises one or more times during formation of the fiber(s) of each layer, independently, one or more or all of the following: altering the volume ratio of the at least one first solvent to the at least one second solvent in the fluid stock(s); adding at least a third solvent to the fluid stock(s); altering the concentration of a conducting agent in the fluid stock(s); and altering the electric potential(s) applied to the nozzle(s), if applied, altering spinneret translation, altering speed of collector rotation, or altering the winding angle and / or predetermined fiber pattern, or the like, where fiber fusion, fiber stacking, or a combination thereof is altered. In various examples, the method further comprises, after the collecting and / or the releasing, heating and / or drying the product. In various examples, the fluid stock(s) further comprise(s) a conductive agent (such as, for example, a salt, a conductive polymer, or any combination thereof.

[0012] In an aspect, the present disclosure provides products. In various examples, a product is a multilayered product. In various examples, a product comprises (or is) a hybrid structure (e.g., comprising at least two different layers comprising different materials). In various examples, a product is made using a system and / or by a method of the present disclosure. A product may be referred to, in the alternative, as a fibrous product.

[0013] In various examples, a product comprises a multilayer structure comprising an inner layer (such as, for example, a core of a tubular structure) comprising one or more porous elastomer(s); and one or more layer(s) of electrowritten fibers (e.g., an outer layer such as for example, a sheath), where at least one of the layer(s) or one or more layer(s) is / are disposed on (e g., on at least portion of) the inner layer (e.g., at least a portion of an exterior surface of the inner layer) comprising the one or more porous elastomer(s). In various examples, the fibers of an individual layer are, independently for each layer, arranged in a predetermined pattern, the average diameter of the fibers is from about 100 nm to about 500 microns, including all 0.1 nm values and ranges therebetween); or the product comprises a desired fiber fusion and / or fiber stacking; or any combination thereof. In various examples, the product comprises two or more structurally and / or compositionally different layers (e.g., two or more structurally and / or compositionally different electrowritten layers (e.g., outer layers or the like). In various examples, one or more of the layer(s) comprises a plurality of fusion points between respective portions of at least two intersected fibers, such that for each fusion point, a bottom surface of a first fiber is bonded to a top surface of a second fiber (such as, for example, the plurality of fusion points between adjacent intersected fibers is observed at an average frequency of about 5% to about 99%, including all 0.1% values and ranges therebetween). In various examples, the electrowritten fibers (e.g., of an individual layer) independently comprise at least one polymer (such as, for example, at least one biocompatible polymer and / or at least one biodegradable polymer). In various examples, the inner layer and / or electrowritten fibers (e.g., of an individual layer) independently comprise at least one chelation crosslinked polymer or the like. In various examples, the product is an implantable medical device or a scaffold of an artificial tissue, or the like. In various examples, a product is a vascular graft (such as, for example, a venous graft, an arterial graft, an arteriovenous graft, or the like). In various examples, the arteriovenous graft comprises a first orifice and a second orifice (e.g., where the first orifice comprises an inner linear dimension that is from about 10% to about 1000%, including all 0.1% values and ranges therebetween) larger than an inner linear dimension of the second orifice and / or the arteriovenous graft comprises a first end and a second end (e.g., the first end comprises an inner diameter and the second end comprises an inner diameter, and the ratio of first end inner diameter to second end inner diameter is from about 1.5: 1 to about 10:1, including all 0.1 ratio values and ranges therebetween and / or the ratio of first end wall thickness to second end wallthickness is from about 1 : 1 .25 to about 1 : 100, including all 0.1 ratio values and ranges therebetween). In various examples, a vascular graft (such as, for example, a venous graft, an arterial graft, an arteriovenous graft, or the like) exhibits desirable compliance (such as, for example, a radial compliance of about 1 to about 80% / 100 mmHg, including all 0.1% values and ranges therebetween.(0014] In various examples, an arteriovenous graft is used in a hemodialysis method. In various examples, a hemodialysis method comprises implanting an arteriovenous graft in an individual and subsequently carrying out hemodialysis on the individual. In various examples, the implanting comprises fluidly connecting (e.g., by suturing or the like) a first orifice (e.g., venous orifice) to a vein of an individual and / or fluidly connecting (e.g., by suturing or the like) a second orifice (e.g., arterial orifice) to an artery of the individual.|00l5( The present disclosure satisfies, inter alia, the need for improved grafts, scaffolds, etc. In particular, the present disclosure provides improved grafts, such as, for example, arteriovenous grafts that are useful in, inter alia, hemodialysis methods.BRIEF DESCRIPTION OF THE FIGURES

[0016] For a fuller understanding of the nature and objects of the disclosure, reference should be made to the following detailed description taken in conjunction with the accompanying figures.

[0017] FIG. 1 shows scanning electron microscopy images of multilayered grafts implanted into sheep common carotid arteries. The majority of the graft consists of porogen leached core consisting of the chelation crosslinked elastomer. The outer layer consists of electrowritten poly(caprolactone) (PCL) fibers as an enforcing sheath.

[0018] FIG. 2 shows ultrasound of grafts 17 days and 100 days after implantation in sheep. B-Mode images show patent grafts with clear lack of thrombus in graft lumen. Doppler Mode images show flow through the graft lumen.

[0019] FIG. 3 shows hematoxylin and Eosin staining (H&E) of native artery and 100 day graft explant shows robust cellular infiltration (dark cell nuclei) and extracellular matrix (grey) deposition throughout the graft. Coverage of remaining graft material (pale voids) suggests approximately 70-80% of graft foreign material had degraded by this time point.

[0020] FIG. 4 shows von Willebrand Factor staining (dark) of native artery and 100 day graft explant shows confluent endothelialization of graft lumen reminiscent of native artery.

[0021] FIG. 5 shows Verhoeff s Elastin staining of native artery and 100-day graft explant shows elastin fiber (black staining) formation in subluminal space. This result suggests elastic neo-artery formation. Elastin deposition in a regenerating artery in adults is a very exciting result that is not commonly observed in synthetic graft applications.

[0022] FIG. 6 shows a sheep Common Carotid Artery (CCA) Interposition model. The SEM image shows the electrowritten PCL sheath, and the cross section of the graft displaying Cu-PAS tubular core with a thin PCL sheath. Part of the electrowriting device is shown.[0023 [ FIG. 7 shows B mode ultrasound image showing the patent graft where lumen is clearly visible and color Doppler mode showing the blood flow at 17 days and 100 days, respectively.

[0024] FIG. 8 shows the gross appearance of sheep CCA explants with various degrees of dilation.

[0025] FIG. 9 shows (a) the graft before implant, (b) ultrasound of the graft including adjacent native artery, and (c) CT angiogram showing the graft with mild dilation.

[0026] FIG. 10 shows Multilayered Cu-PPIAS Graft. A - The inner lumen of the graft showing the fiber angle of Layer #1 - 45°. B - The outer ablumen of the graft showing the fiber angle of Layer #2 - 55°. C - Single loop suture retention test demonstrated a -24% increase in suture retention strength by changing the outer 10% of the graft to a differently patterned layer. D - Uniaxial tensile testing of the two grafts showed no significant difference in elastic modulus with modification to outer graft layer, but a significant change in ultimate tensile strength was observed, which is representative of the increased suture retention strength.DETAILED DESCRIPTION OF THE DISCLOSURE

[0027] Although claimed subject matter will be described in terms of certain examples, other examples, including examples that do not provide all of the benefits and features set forth herein, are also within the scope of this disclosure. Various structural, logical, and process step changes may be made without departing from the scope of the disclosure.

[0028] As used herein, unless otherwise stated, "about," "approximately," “substantially,” or the like, when used in connection with a measurable variable such as, for example, a parameter, an amount, a temporal duration, or the like, are meant to encompass variations of, for example, a specified value including, for example, those within experimental error (which can be determined by for example, a given data set, an art accepted standard, and / or with a givenconfidence interval (e.g. 90%, 95%, or more confidence interval from the mean), such as, for example, variations of -+7-10% or less, + / -5% or less, + / -1% or less, and + / -0.1% or less of and from the specified value), insofar such variations are appropriate to perform in the context of the disclosure. As used herein, unless otherwise stated, the terms “about,” “approximate,” “at or about,” and “substantially” can mean that the amount or value in question can be the exact value or a value that provides equivalent results or effects as recited in the sample claims or taught herein. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but may be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error, and the like, and other factors known to those of skill in the art such that, for example, equivalent results, effects, or the like are obtained. In some circumstances, the value that provides equivalent results or effects cannot be reasonably determined. In general, an amount, size, formulation, parameter or other quantity or characteristic is “about,” “approximate,” or “at or about” whether or not expressly stated to be such. It is understood that where “about,” “approximate,” or “at or about” is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise.|0029| Ranges of values are disclosed herein. The ranges set out a lower limit value and an upper limit value. Unless otherwise stated, the ranges include the lower limit value, the upper limit value, and all values between the lower limit value and the upper limit value, including, but not limited to, all values to the magnitude of the smallest value (either the lower limit value or the upper limit value) of a range. It is to be understood that such a range format is used for convenience and brevity, and thus, should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. To illustrate, a numerical range of “about 0.1% to 5%” should be interpreted to include not only the explicitly recited values of about 0.1% to about 5%, but also, unless otherwise stated, include individual values (e.g., about 1%, about 2%, about 3%, and about 4%) and the sub-ranges (e.g., about 0.5% to about 1.1%; about 0.5% to about 2.4%; about 0.5% to about 3.2%, and about 0.5% to about 4.4%, and other possible sub-ranges) within the indicated range. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the valueitself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about, it will be understood that the particular value forms a further disclosure. For example, if the value “about 10” is disclosed, then “10” is also disclosed.(0030] As used herein, unless otherwise stated, the term “biodegradable polymer” describes a polymer that can be cleaved either enzymatically and / or hydrolytically to break it down sufficiently so as to allow the body to absorb or clear it away. A biodegradable graft is a graft in which at least a significant portion (e.g., at least 50%) of the graft degrades within one year or less of implantation.(0031] As used herein, unless otherwise stated, the terms “coating”, “coatings”, “coated” and “coat” are forms of the same term defining material and process for making a material where a first substance or substrate surface is at least partially covered or associated with a second substance. Both the first and second substance are not required to be different. Further, when a surface is “coated” as used herein, unless otherwise stated, the coating can be effectuated by any chemical or mechanical bond or force, including linking agents. The “coating” need not be complete or cover the entire surface of the first substance to be “coated”. The “coating” may be complete as well (e.g., approximately covering the entire first substance). There can be multiple coatings and multiple substances within each coating. The coating may vary in thickness or the coating thickness may be substantially uniform. Coatings contemplated in accordance with the present disclosure include, but are not limited to, medicated coatings, drug-eluting coatings, drugs or other compounds, pharmaceutically acceptable carriers and any combination thereof, or any other organic, inorganic or organic / inorganic hybrid materials. In an example, the coating is a thromboresistant coating which has anticoagulant properties, such as, for example, heparin or the like, or any combination thereof.|0032| As used herein, unless otherwise stated, the term “scaffold” describes a structural support facilitating cell infiltration and attachment in order to guide vessel growth. In some examples, a scaffold is biodegradable, bioresorbable, or the like, or any combination thereof. In some examples, a scaffold is a biodegradable polymer (e.g., polyester) scaffold. In some examples, a scaffold is used to form a vascular graft.

[0033] As used herein, unless otherwise stated, the term “vascular graft” describes a tubular member which acts as an artificial vessel. A vascular graft can include a single material, a blend of materials, a weave, a laminate or a composite of two or more materials.

[0034] As used herein, unless otherwise stated, the term “aligned” or “aligned fibers” or “aligned nozzles” describes a set of elements (e.g., fibers, nozzles, or the like) which have a substantially parallel (e.g., parallel) arrangement along one or more axial directions.

[0035] As used herein, unless otherwise stated, the term “layer” describes a region of a continuous fiber or groups of continuous fibers traversing at least a portion (e.g., a desired portion), substantially all, or all of the perimeter of the fibrous product and at least a portion (e.g., a desired portion), substantially all, or all of the length of the fibrous product formed during a single pass or two or more passes of the spinneret of a solution electrowriting system along the length of the collector system. Alternately, the term “layer” can describe a region of continuous fiber or groups of continuous fibers in a fibrous product at a substantially constant distance from the inner wall of the fibrous product. As used herein, unless otherwise stated, a layer can be further defined by structural and / or compositional features including, but not limited to, fiber angle, degree of fiber fusion (which may also be referred to as level of fiber fusion), degree of fiber stacking, degree of porosity, average pore width, shape of pores, fiber diameter, conduit wall thickness, fiber material(s), fiber additive(s), or the like or any combination thereof. As used herein, unless otherwise stated, a static layer has substantially the same structural and / or compositional features along the length of the fibrous product. As used herein, unless otherwise stated, a dynamic layer has variable structural and / or compositional features along the length of the fibrous product. A dynamic layer may have two or more distinct regions along the length of the fibrous product, each having substantially different structural and / or compositional features. The two or more distinct regions may vary continuously along at least a portion (e g., a desired portion), substantially all, or all of the longitudinal axis of the fibrous product. In various examples, a layer comprises two or more individual layers.

[0036] As used herein, unless otherwise stated, the term “nozzle” is used interchangeably with “spinneret” (e.g., the needle of a syringe, or the like). As used herein, unless otherwise stated, an “array” of nozzles comprises a plurality of the nozzles each arranged in a selected and / or desired pattern and aligned with respect to one another in one or more axial dimension(s).

[0037] As used herein, unless otherwise stated, the term “power source” is used interchangeably with “high voltage power supply” and the term “electric potential” is used interchangeably with “voltage”.

[0038] As used herein, unless otherwise stated, the term “reservoir” is used interchangeably with a “container” (e.g., a syringe, a pump, a mixing chamber, a syringe pump, or the like). As used herein, unless otherwise stated, the term “fluid stock” can be a solution, a suspension, an emulsion, or the like.|0039| As used herein, unless otherwise stated, the term “polar solvents” are solvents having larger dipole moments (or partial charge) due to the larger electronegativity difference between the bonded atoms (such as, for example, between oxygen and nitrogen, or the like) and the shape and geometry of the molecule. As used herein, unless otherwise stated, the term “non-polar solvents” are solvents having smaller dipole moments (or partial charge) due to the smaller electronegativity difference between the bonded atoms (such as, for example, between carbon and hydrogen, or the like) and the shape and geometry of the molecule. Solvent polarity increases with increasing dipole moment. As used herein, unless otherwise stated, a non-polar solvent will have a dipole moment in the range of 0-1.5 Debye units (D), while a polar solvent will have a dipole moment in the range of 1.5-4.2 D. Solvent polarity can alternately be measured the dielectric constant (or permittivity) of a solvent, which similarly increases with solvent polarity.

[0040] As used herein, unless otherwise stated, the term “thermo-reactive” refers to materials which react (e.g., denature, degrade, crosslink, or otherwise change, or any combination thereof) at a specified temperature. Non-limiting examples of thermo-reactive materials include thermosetting materials, and thermo-degradable polymers (e.g., polymers which undergo thermal depolymerization, chain scission, removal of polymer side groups, polymer oxidation, or the like, or any combination thereof). Non-limiting examples of thermo-reactive materials include proteins, growth factors and cytokines: vascular endothelial growth factors (VEGF), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), epidermal growth factor (EGF), fibroblast growth factors (FGF), transforming growth factors (TGF-|31, TGF-02, TGF-03), interleukins (IL-1-17), ephrins, colony stimulating factors (CSF), bone morphogenic proteins (BMP), neurotrophin-3 (NT-3), platelet derived growth factor (PDGF), and the like, and any combination thereof. Non-limiting examples of thermo-reactive additives (e.g., thermo-degradable additives, or the like) include pharmaceutical compounds and temperature indicators. Non-limiting examples of thermo-reactive pharmaceutical compounds include rapamycin, tamoxifen, acetaminophen, ibuprofen, diclofenac, paclitaxel, amoxicillin, gentamicin, doxorubicin, cyclodextrin, naproxen, indomethacin, ketoprofen, metronidazole, ciprofloxacin, curcumin, insulin, lovastatin, and other drugs used as antimicrobials, anti-inflammatory agents, antineoplastics, statins, and the like, and any combination thereof. Non-limiting examples of thermo-reactive additives include indicators and the like, and any combination thereof. Nonlimiting examples of thermo-reactive indicators include fluorescein isothiocyanate (FITC), rhodamine b, and the like and any combination thereof.(0041 ] The present disclosure provides, inter alia, products, such as, for example, multilayered grafts and the like. The present disclosure also provides systems for and methods of making products, such as, for example, multilayered grafts and the like.

[0042] In an aspect, the present disclosure provides methods of making products. In various examples, a method comprises an electrowriting method or methods. In various examples, using particular components and / or conditions the methods provide fibrous products having desirable fiber fusion and / or fiber stacking. In various examples, a method is carried out using a system as described herein. Non-limiting examples of methods of making products are provided herein.

[0043] In various examples, a method of making a product (such as, for example an electrowritten product (e.g., a solution electrowritten product) comprises ejecting one or more fluid stream(s) of one or more fluid stock(s) from one or more nozzle(s) of an electrowriting system (e.g., an electrowriting system, such as, for example, a solution electrowriting system (e.g., of the present disclosure) to form a plurality of fiber(s); and collecting the plurality of fiber with a collector system to form a fibrous product comprising the plurality of fiber arranged in a predetermined pattern disposed on at least a portion of the exterior surfaces of a layer comprising one or more porous elastomer(s); and releasing the fibrous product from the collector system. In various examples, a desired fiber fusion and / or a desired fiber stacking is observed in the product.

[0044] In various examples, a method comprises providing an elastomer (e.g., a biodegradable elastomer or the like), which may be porous, inner layer (e.g., a core or the like) (which may comprise a single layer or a plurality of individual layers) (e.g., comprising one or more chelation crosslinked polymer(s)) (e.g., comprising porous poly (propanedi ol-co-(hydroxyphenylmethylene)amino-propanediol sebacate (PAS), a metal (such as, for example, copper or the like) crosslinked PAS, or the like); forming one or more fiber(s) by electrowriting (e.g., forming one or more fiber(s) from a jet stream, which is formed from one or more fluid stocks(s)) on at least a portion of or all of the exterior surfaces of the porous elastomer inner layer. In various examples, the forming one or more fiber(s) by electrowriting forms an outer layer (e.g., a sheath or the like) (which may comprise a single layer or a plurality of individual layers) disposed on the inner layer. In various examples, a product (such as, for example, a product comprising a hybrid structure or the like) is formed. In various examples, an inner layer comprises one or more elastomer(s) (e.g., a biodegradable elastomer or the like), which may be porous, or the like. In various examples, one or more or all of the elastomer(s) is / are metalloelastomer(s) (e.g., a porous metalloelastomer, which may be biodegradable) (e.g., one or more chelation crosslinked polymer(s) or the like) (e.g., an inner layer, a core or the like), or the like.[0045| Various inner layers (e.g., cores) can be used. In various examples, an inner layer (e.g., a core) is a porous inner layer (e.g., a porous core). In various examples, an inner layer (e g., a core) is a fibrous inner layer (e.g., a fibrous core), for example, comprising a plurality of fibers. In various examples, an inner layer (e.g., a core) is an electrowritten inner layer. In various examples, an inner layer (e.g., a core) is a non-fibrous inner layer (e.g., non-fibrous core).

[0046] In various examples, an inner layer is formed using a porous polymer template (such as, for example using one or more sacrificial porogen(s) (such as, for example, salt(s) (e.g., sodium chloride or the like), polymer(s), or the like (which may be in the form of particulates, beads, or the like, which may be appropriate size to provide a template comprising desired porosity) (e.g., sodium chloride particulates, poly (methyl methacrylate) (PMMA) beads), which may be partially fused to form a porous template). In various examples, substantially all or all of the porous template (or porogen(s)) is removed (such as, for example, by contacting the template with a solvent or mixture of solvents, thermal treatment, or the like).

[0047] In various examples, electrowriting of an outer layer (e.g., a sheath) comprises (or is) a method or methods and / or a material or materials as described in International Patent Application No. PCT / US2021 / 056351, fded October 22, 2021 and titled “SolutionElectrowriting”, the disclosure of which is incorporated herein by reference. In various examples, an outer layer is not formed by electrospinning.

[0048] In various examples, a method comprises providing and / or using an electrowriting system (such as, for example, a solution electrowriting system). In various examples, an electrowriting system (such as, for example, a solution electrowriting system) is used (e.g., in a method of the present disclosure or the like) to make a product (such as, for example, a multilayered graft or like of the present disclosure) (e.g., an inner layer or one or more layer(s) thereof and / or an outer layer or one or more layer(s) thereof. Non-limiting examples of solution electrowriting systems are described herein.

[0049] A system can have various combinations of components and / or configurations. In various examples, a system comprises: a plurality of nozzles; a material supply system comprising one or more reservoir(s) fluidically coupled to the nozzles and configured to supply one or more fluid stock(s) to the nozzles thereby ejecting one or more jet stream(s) of the fluid stock(s) from the nozzles; a collector system configured to collect one or more fiber(s) formed by the jet stream(s) ejected from the nozzles; and, optionally, one or more power source(s) configured to provide one or more electric potential(s) to each of the nozzles and, optionally, to the collector system, thereby providing one or more electric potential difference(s) between the collector system and each of the nozzles.

[0050] In various examples, a system comprises a two-dimensional (2D) (e.g., flat) collector system or a three-dimensional (3D) (e.g., cylindrical) collector system. A system can comprise various nozzle arrangements between each nozzle, between the nozzles and the collector system, or any combination thereof. In various examples, the tip of each nozzle is oriented toward a surface of the collector system. In various examples, the plurality of nozzles comprises at least three nozzles. In various examples, the plurality of nozzles comprises one or more array(s) of nozzles. In various examples, the one or more array(s) of nozzles comprise(s) a linear array of nozzles, a radial array of nozzles, or the like, or any combination thereof. In various examples, the linear array of nozzles is aligned along the longitudinal axis of and oriented toward a surface of the collector system. In various examples, the radial array of nozzles is positioned around and oriented toward a surface of the perimeter (e.g., the circumference) of the collector system. In various examples, the nozzles have a tip-to-tip separation distance of about 1 mm to about 300 mm, including all 0.1 mm values and ranges therebetween. In various examples, the same fluidstock is supplied to all nozzles. In various examples, different fluid stocks are supplied to all nozzles. In various examples, different fluid stocks are supplied to two or more nozzles. In various examples, different fluid stocks are supplied to two or more nozzles of one or more arrays of the nozzles (e.g., a linear array, a radial array, or the like, or any combination thereof).

[0051] In various examples, a collector system comprises a mandrel (such as, for example, a stainless-steel mandrel or the like) and a layer comprising one or more porous elastomer(s) (e.g., at least a portion or all of which may be porous biodegradable elastomer(s) or the like) (e.g., metalloelastomer(s), such as, for example, porous metalloelastomer(s), any one or all of which may be biodegradable, or the like) (e.g., porous elastomer(s) independently comprising one or more chelation crosslinked polymer(s)) (such as, for example, PAS or the like, or any combination thereof) disposed on the mandrel.|0052[ A collector system may include a water-soluble sacrificial layer. In various examples, the collection system comprises a water-soluble sacrificial layer on the surface upon which the fibers are collected. In such cases, the releasing may comprise dissolving the sacrificial layer in water. In various examples, the sacrificial layer comprises sodium hyaluronate (HA), polyvinyl alcohol, polyvinylpyrrolidone, gelatin, collagen, chitosan, glucose, sucrose, dextran, or the like, or any combination thereof.

[0053] In various examples, the plurality of nozzles comprise a first nozzle or a first array of nozzles configured to form a group of fibers aligned in a first direction, and a second nozzle or a second array of nozzles configured to form a group of fibers aligned in a second direction, where the first direction and the second direction form an angle with a degree of about 0° to about 90°, including all 0.1° values and ranges therebetween. In various examples, the first direction and the second direction form an angle with a degree of about 0° to about 90°, from about 15° to about 90°, from about 25° to about 80°, or more preferably from about 35° to about 75°, including all 0.1° values and ranges therebetween.

[0054] A system can comprise various material supply systems. In various examples, the material supply system is configured to deliver a single fluid stock or at least two fluid stocks from at least two reservoirs for at least one nozzle (such as, for example, delivering at least two fluid stocks into one nozzle or delivering different fluid stocks to different nozzles).|0055| A system may comprise a motorized stage. In various examples, the system further comprises a motorized stage configured to move one or more or all of the nozzles or one or morearray(s) of the nozzles parallel to the longitudinal axis of the collector system during the electrowriting; and / or where one or more or all of the nozzles or one or more array(s) of the nozzles is / are configured to move parallel to the longitudinal axis of the collector system during electrowriting. In various examples, the motorized stage moves at a speed of about 0.5 cm / s to about 20 cm / s or preferably from about 1 cm / 1 to about 15 cm / s, including all 0.01 cm / s values and ranges therebetween.|0056| A system may comprise a movable collector system. Non-limiting examples of a moving collector system include a rotating mandrel, a Modular Rotating Collector System, or a motorized stage configured to move the collector system. In various examples the movable collector system is a mandrel having a diameter of about 0.5 mm to about 30 mm. In various examples, the mandrel has a uniform diameter or a tapered diameter along the length of the mandrel. In various examples, the movable collector system is a rotating mandrel having a rotation speed (VR) selected from about 0.5 cm / s to about 20 cm / s including all 0.01 cm / s values and ranges therebetween or preferably from about 1 cm / s to about 10 cm / s including all 0.01 cm / s values and ranges therebetween.

[0057] A system can comprise various distances between the collector system and the nozzles. In various examples, the collector system is positioned at a distance from the nozzles of about 500 microns to about 50 mm, including all 1 micron values and ranges therebetween. In various examples, the collector system is positioned at a distance from the nozzles of less than about 50 mm, preferably in a range from about 500 microns to about 30 mm, including all 1 micron values and ranges therebetween or more preferably in a range from about 1 mm to about 20 mm, including all 1 micron values and ranges therebetween.

[0058] In various examples, this disclosure uses the same components as a standard electrospinning device: syringe pump, power supply, and a rotating fiber collection mandrel. In various examples, a motorized stage / platform is used to program motion of the electro-spinning spinneret and / or the collection mandrel.

[0059] In various examples, a fluid stock described herein for the electrowriting systems and / or methods is used in conventional electrospinning systems and / or methods to improve the fiber fusion and / or achieve desirable fiber alignments.

[0060] In various examples, a system is a modified standard extrusion-based 3D printer. In various examples, the conventional extrusion print head is replaced with a syringe pump andpower supply and the standard flat 3D printer sample deposition platform replaced with a rotating mandrel to create a device with very similar functionality. In various examples, a system is an extrusion-based 3D printer comprising a syringe pump, power supply, and a rotating mandrel.

[0061] In various examples, a method further comprises collecting the fiber(s) to form a fibrous product comprising one or more fiber(s) arranged in a predetermined pattern. In various examples, a method further comprises collecting the fiber(s) to form a fibrous product, where a desired fiber fusion and / or a desired fiber stacking is observed in the fibrous product. A fibrous product can have various predetermined patterns. In various examples, a predetermined pattern is a particular predetermined three-dimensional shape and / or a particular predetermined fiber orientation (e.g., fiber fusion, fiber stacking, winding angle, or any combination thereof).|0062| In various examples, a method comprises providing a solution electrowriting system comprising: one or more nozzle(s); a material supply system comprising one or more reservoir(s) fluidically coupled to the nozzle(s) and configured to supply one or more fluid stock(s) to the nozzle(s) thereby ejecting one or more jet stream(s) of the fluid stock(s) from the nozzle(s); a collector system configured to collect one or more fiber(s) formed by the jet stream(s) ejected from the nozzle(s); and, optionally, one or more power source(s) configured to provide one or more electric potential(s) to each of the nozzle(s) and, optionally, to the collector system, thereby providing one or more electric potential difference(s) between the collector system and each of the nozzle(s). In various examples, the method further comprises ejecting the fluid stream(s) of the fluid stock(s) from the nozzle(s) to form the fiber(s). In various examples, the method further comprises collecting the fiber(s) with the collector system to form a fibrous product comprising one or more fiber(s) arranged in a predetermined pattern. In various examples, the method further comprises releasing the fibrous product from collector system, where a desired fiber fusion and / or a desired fiber stacking is observed in the fibrous product.[0063| A method may also include heating and / or drying the fibrous product. A method may also include irradiating the fibrous product with electromagnetic radiation (e.g., UV radiation, or the like, or any combination thereof), ionizing radiation (e.g., electron beam (EB) radiation, or the like, or any combination thereof), or the like, or any combination thereof. In various examples, the fibrous product is cured, crosslinked, or the like, or any combination thereof, by the heating, the irradiating, or the like, or any combination thereof. In various examples, dryingcomprises thermal drying (e.g., heating), therm al -vacuum drying, freeze-vacuum drying, air drying, fan drying, desiccant drying, or the like, or any combination thereof.

[0064] In various examples, a method further comprises, after the collecting and / or the releasing, heating and / or drying the fibrous product. In various examples, the heating comprises heating the fibrous product at a temperature from about 50 °C to about 160 °C, from about 70 °C to about 150 °C, or from about 80 °C to about 110 °C, or at least about 60 °C, at least about 70 °C, at least about 80 °C, at least about 90 °C, or at least about 100 °C, or at most about 200 °C, at most about 170 °C, at most about 150 °C, or at most about 120 °C.

[0065] A method can use a system comprising various fluid stock(s). In various examples, each fluid stock comprises a solution comprising at least one first solvent and, optionally, at least one second solvent, and one or more material(s) configured to form at least a portion of a fiber upon ejection of the jet stream(s) of the fluid stock(s) from the nozzle(s). In various examples, the material(s) is / are dissolvable in at least one of the solvent(s) to form a solution.

[0066] A method can achieve a desired degree of fiber fusion using various fluid stock(s) comprising at least one first solvent and at least one second solvent having various boiling point(s). In various examples, the fluid stock(s) comprise at least one first solvent having a boiling point of less than about 80 °C, and at least one second solvent having a boiling point of at least about 80 °C or greater. In various examples, the at least one first solvent has a boiling point of less than about 80 °C (or less than about 90 °C, or less than about 75 °C, or less than about 70 °C, or less than about 65 °C, or less than about 60 °C, or less than about 55 °C, or less than about 50 °C, or less than about 45 °C); and the at least one second solvent has a lower volatility than the first solvent, wherein the at least one second solvent has a boiling point of at least about 80 °C, at least about 90 °C, at least about 100 °C, at least about 110 °C, at least about 120 °C, at least about 130 °C, at least about 140 °C, or at least about 150 °C.

[0067] A fluid stock may include at least one first solvent and at least one second solvent. In various examples, the fluid stock(s) comprise(s) at least one first solvent and at least one second solvent, where the boiling point of the at least one second solvent is from about 10 °C to about 200 °C, including all 0.1 °C values and ranges therebetween, higher than the boiling point of the at least one first solvent. In various examples, the at least one first solvent has a high volatility, wherein the at least one second solvent has a lower volatility than the first solvent (e.g., the second solvent has a boiling point of at least about 10 °C higher (or at least about 20 °C higher,or at least about 30 °C higher, or at least about 40 °C higher, or at least about 50 °C higher, or at least about 60 °C higher, or at least about 70 °C higher, or at least about 80 °C higher, or at least about 90 °C higher, or at least about 100 °C higher, or at least about 110 °C higher) than the first solvent).

[0068] In various examples, the at least one first solvent is chosen from diethyl ether, di chloromethane (DCM), acetone, 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), chloroform, methanol, tetrahydrofuran (THF), trifluoroethanol (TFE), ethanol, acetonitrile, cyclohexane, benzene, ethyl acetate, hexane, trifluoroacetic acid, isopropanol, and the like, and any combination thereof. In various examples, the at least one second solvent is chosen from water, dioxane, toluene, pyridine, N,N-dimethylformamide (DMF), anisole, dimethyl sulfoxide (DMSO), 1,2-di chloroethane, tri ethylamine, heptane, butanol, acetic acid, xylene, diglyme (diethylene glycol diethyl ether), and the like, and any combination thereof. In various examples, the volume ratio of the at least one first solvent to the at least one second solvent is from about 1 :99 to about 99: 1, including all integer volume ratio values and ranges therebetween. In various examples, the fibers comprise a plurality of fusion points between two intersected fibers, such that for each fusion point, a bottom surface of a first fiber is bonded to a top surface of a second fiber. In various examples, the plurality of fusion points between two intersected fibers is observed at an average frequency of about 5% to about 99%, including all 0.1% values and ranges therebetween.

[0069] A method can form various products. Non-limiting examples of products include grafts (such as, for example, tissue grafts, vascular grafts (e.g., venous grafts, arterial grafts, arteriovenous grafts and the like), and the like), scaffolds, and the like). In various examples, a method provides a product described herein.

[0070] A method can achieve a desired degree of fiber fusion using various fluid stock(s) comprising at least one first solvent having various boiling point(s). In various examples, the fluid stock(s) comprise(s) at least one first solvent having a boiling point of about 70 °C to about 120 °C, including all 0.1 °C values and ranges therebetween. In various examples, the at least one first solvent is chosen from trifluoroethanol (TFE), ethanol, acetonitrile, cyclohexane, benzene, ethyl acetate, hexane, trifluoroacetic acid, isopropanol, water, dioxane, toluene, pyridine, and the like, and any combination thereof. In various examples, the fibers comprise a plurality of fusion points between two intersected fibers, such that, for example, for each fusion point, a firstsurface (e.g., a bottom surface) of a first fiber is bonded to a second surface (e.g., a top surface), which may be proximate to the first surface of the first fiber, of a second fiber. In various examples, for at least one or more or all fusion points, the overlapped distance of the first fiber and the second fiber is less than about 15%, less than about 10%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about 1% of the diameter of the first fiber and / or second fiber.

[0071] In various examples, the plurality of fusion points between two intersected fibers is observed at an average frequency of about 5% to about 99%, including all 0.1% values and ranges therebetween. In various examples, the fibers comprise an average frequency of fusion points of about 5% to about 99%, or from about 5% to about 90%, or from about 10% to about 60%, or at least about 5%, or at least about 7%, or at least about 10% , or at least about 15 %, or at least about 20%, or at least about 30%, or at most about 99 %, or at most about 90 %, or at most about 80%, or at most about 70 %, or at most about 60 %, or at most about 50%, including all 1% values and ranges therebetween.[0072J A method can achieve a desired degree of fiber stacking using various fluid stock(s) comprising at least one first solvent and at least one second solvent having various dipole moment(s). In various examples, the fluid stock(s) comprise(s) at least one first solvent and at least one second solvent, where the at least one first solvent has a dipole moment of about 1.5 D to about 4.2 D, including all 0.1 D values and ranges therebetween, and the at least one second solvent has a dipole moment of about 0 D to less than about 1.5 D, including all 0.1 D values and ranges therebetween. In various examples, the fluid stock(s) comprise(s) at least one first solvent and at least one second solvent, and where the dipole moment of the at least one first solvent is about 20 % or more greater than the dipole moment of the at least one second solvent. In various examples, the at least one first solvent is chosen from dichloromethane, tetrahydrofuran (THF), pyridine, trifluoroethanol, acetone, ethanol, methanol, N,N-Dimethylformamide, dimethyl sulfoxide (DMSO), isopropanol, water, ethyl acetate, trifluoroacetic acid, 1, 1,1, 3,3,3- hexafluoroisopropanol, 1-butanol, 1,2-dichloroethane, acetic acid, diglyme, acetonitrile, and the like, and any combination thereof. In various examples, the at least one second solvent is chosen from cyclohexane, hexane, benzene, toluene, dioxane, diethyl ether, chloroform, anisole, triethylamine, heptane, xylene, and the like, and any combination thereof. In various examples, the volume ratio of the at least one first solvent to the at least one second solvent is from about1 :99 to about 99: 1 , including all integer volume ratio values and ranges therebetween. In various examples, for each axial direction of the fibrous product, adjacent fibers of different layers are aligned over one the other and are vertically stacked.

[0073] The method can achieve a desired degree of fiber stacking using various fluid stock(s) comprising at least one first solvent having various dipole moment(s). In various examples, the fluid stock(s) comprise(s) at least one first solvent having a dipole moment of about 1.5 D to about 4.2 D, including all 0.1 D values and ranges therebetween. In various examples, the at least one first solvent is chosen from dichloromethane, tetrahydrofuran (THF), pyridine, trifluoroethanol, acetone, ethanol, methanol, N,N-Dimethylformamide, dimethyl sulfoxide (DMSO), isopropanol, water, ethyl acetate, trifluoroacetic acid, 1, 1,1, 3,3,3- hexafluoroisopropanol, 1-butanol, 1,2-dichloroethane, acetic acid, diglyme, acetonitrile, and the like, and any combination thereof. In various examples, for each axial direction of the fibrous product, adjacent fibers of different layers are aligned over one the other and are vertically stacked.(0074] The method can achieve a desired degree of fiber stacking using various fluid stock(s) comprising at least one first solvent and optionally, at least one second solvent and can have various conductivit(ies). In various examples, the fluid stock(s) further comprise(s) a conductive agent. In various examples, the conductive agent is chosen from a salt, a conductive polymer, and the like, and any combination thereof.(0075] Various salts can be used. Combinations of salts may be used. In various examples, the salt is chosen from potassium iodide, potassium bromide, potassium chloride, sodium iodide, sodium bromide, sodium chloride, potassium fluoride, sodium fluoride, lithium iodide, lithium bromide, lithium chloride, lithium oxide, sodium hydride, lithium hydride, and the like, and any combination thereof. In various examples, the conductive polymer is chosen from polypyrroles, polycarbazoles, polyindoles, polyazepines, polyanilines, polyfluorenes, polyphenylenes, polypyrenes, polyazulenes, polynapthalenes, polythiophenes, polyacetylenes, and the like, and any combination thereof.

[0076] In various examples, the salt is present in the fluid stock(s) at from about 0.01 weight % to about 10 weight %, including all 0.1 weight % values and ranges therebetween, based on the total weight of the material(s), or where the conductive polymer is present in the fluid stock(s) at from about 0.1 weight % to about 100 weight %, including all 0.1 weight % valuesand ranges therebetween, based on the total weight of the material(s). In various examples, for each axial direction of the fibrous product, adjacent fibers of different layers are aligned over one the other and are vertically stacked.

[0077] The method can achieve a desired degree of fiber fusion using various fluid stock(s) comprising at least one first solvent and optionally, at least one second solvent and by applying various electric potentials can be applied to the nozzle(s). In various examples, the electric potential applied to the nozzle(s) is from about 50V to about 8kV, including all O.lkV values and ranges therebetween. In various examples, the electric potential applied to the nozzle(s) is selected from a range of about 100V to about 8kV, preferably a range of about 100V to about 5000V, or more preferably a range of about 1000V to about 5000V, or at least about 100 V, at least about 200 V, at least about 500 V, at least about IkV, or less than about lOkV, less than about 8 kV, less than about 5 kV, less than about 4kV, or less than about 3kV, including all 0. IkV values and ranges therebetween. In various examples, for each axial direction of the fibrous product, adjacent fibers of different layers are aligned over one the other and are vertically stacked.

[0078] The method can form a fibrous product comprising one or more fiber(s) arranged in various predetermined patterns. In various examples, the fibrous product comprises one or more layer(s) and each layer (or individual layers comprising a layer) comprises one or more group(s) of fibers independently and optionally aligned in one or more axial direction(s) of the fibrous product within and / or between the layer(s). In various examples, the group(s) of fibers is / are uniaxially, biaxially, or multi-axially oriented within and / or between the layer(s). In various examples, each group of fibers in a layer (or an individual layer of a layer) has a substantially constant winding angle, relative to the longitudinal axis of the fibrous product. In various examples, the substantially constant winding angle is from about 1° to about 89°, including all 0.1° values and ranges therebetween, relative to the longitudinal axis of the fibrous product. In various examples, the fibrous product comprises two groups of aligned fibers aligned in two directions with a substantially constant winding angle from about 15° to about 90°, from about 25° to about 80° or more preferably from about 35° to about 75°, including all 0.1° values and ranges therebetween, relative to the longitudinal axis of the product. In various examples, two adjacent individual layers or two or more pairs of adjacent individual layers (e.g., of an outer layer or sheath) comprise different winding angles.

[0079] The method may use a power source providing various electrical potential(s) to the nozzle(s). In various examples, the electric potential is from about 50V to about 8kV, including all 0.1 kV values and ranges therebetween. In various examples, the electric potential applied to the nozzle(s) is selected from a range of about 100V to about 8kV, preferably a range of about 100V to about 5000V, or more preferably a range of about 1000V to about 5000V, or at least about 100 V, at least about 200 V, at least about 500 V, at least about IkV, or less than about lOkV, less than about 8 kV, less than about 5 kV, less than about 4kV, or less than about 3kV, including all O.lkV values and ranges therebetween.

[0080] The method can use various fluid stock(s). In various examples, the volume ratio of the at least one first solvent to the at least one second solvent is from about 1:99 to about 100:0, including all integer volume ratio values and ranges therebetween. In various examples, the volume ratio of the at least one first solvent to the at least one second solvent is 100:0 or is from about 1 :99 to about 99: 1, from about 1:9 to about 9: 1, from about 1 :4 to about 4: 1, or from about 1 :3 to about 3 : 1, or is from at least about 1 :99, about 1 :9, about 1 :8, about 1 :7, about 1 :6, about 1 :5, about 1 :4, about 1 :3, about 1 :2, or is about 1 : 1, or is at most about 99: 1, about 9: 1, about 8: 1, about 7:1, about 6:1, about 5: 1, about 4: 1, about 3: 1, about 2: 1, or about 1 : 1, including all integer volume ratio values and ranges therebetween.

[0081] In various examples, the at least one first solvent is from about 10% to about 100%, including all 1% values and ranges therebetween, based on the volume of the total solvent, or from about 20% to about 80%, including all 1% values and ranges therebetween, based on the volume of the total solvent, or preferably from about 25% to about 75%, including all 1% values and ranges therebetween, based on the volume of the total. In various examples, the temperature of the fluid stock(s) is less than about 80 °C, less than about 70 °C, less than about 60 °C, less than about 50 °C, less than about 40 °C, less than about 30 °C before, during and / or after the fluid stock(s) is / are ejected from the nozzle(s).[00821 The fluid stock(s) can comprise various material(s). In various examples, the one or more material(s) comprise at least one polymer. In various examples, the at least one polymer comprises at least one biocompatible polymer, at least one biodegradable polymer, or the like, or any combination thereof. In various examples, the at least one polymer is thermo-reactive at a temperature of at least about 60 °C. In various examples, the at least one polymer is thermo- reactive at a temperature of at least 60 °C, at least 100 °C, at least 150 °C, at least 166 °C, at least170 °C, at least 180 °C, at least 190 °C, at least 200 °C, at least 210 °C, at least 220 °C, at least 230 °C, at least 240 °C, at least 250 °C, at least 260 °C, at least 270 °C, at least 280 °C, at least 290 °C, or at least 300 °C.

[0083] A fluid stock can comprise various polymers or combinations of polymers. In various examples, the at least one polymer comprises at least one prepolymer (e.g., a polymer precursor, or the like, or any combination thereof) comprising at least one reactive polymer and, optionally, at least one unreacted monomer, at least one polymerization catalyst, at least one crosslinking agent, or the like, or any combination thereof. In various examples, the at least one prepolymer is curable (e.g., polymerizable, crosslinkable, or the like, or any combination thereof) by heating, electromagnetic radiation curing (e.g., UV curing, or the like, or any combination thereof), ionizing radiation curing (e.g., electron beam (EB) curing), or the like, or any combination thereof), or the like, or any combination thereof. In various examples, the at least one polymer comprises a crosslinked polymer, hydrogel, or the like, or any combination thereof. In various examples, the at least one polymer does not comprise a crosslinked polymer, hydrogel, or the like, or any combination thereof.

[0084] In various examples, the at least one polymer, is a synthetic organic polymer, a natural organic polymer, or an inorganic polymer. In various examples, the at least one polymer is chosen from a polyester, polyurethane, polyether, polyketal, polyamide, polyimide, polycarbonate, polyacrylate, polysaccharide, and the like, and any combination thereof. In various examples, the at least one polymer is chosen from polyglycolide or a polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone (PCL), polyhydroxyalkanoate (PHA), polyhydroxybutyrate (PHB), polyethylene adipate (PEA), polybutylene succinate (PBS), poly(3- hydroxybutyrate-co-3 -hydroxy valerate) (PHBV), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyethylene glycol (PEG), polytrimethylene terephthalate(PTT), polyethylene naphthalate (PEN), poly(glycerol-sebacate) (PGS), palmitate functionalized poly(glycerol sebacate (PGSP), poly(epsilon caprolactone) (PCL), polymethyl methacrylate (PMMA), chitosan, gelatin, cellulose, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), polydioxanone, derivatives thereof, and the like, and any combination thereof. In various examples, the at least one polymer is chosen from silk, gelatin, and a polysaccharide, such as, for example, cellulose, chitin, chitosan, hyaluronic acid, dextran, and alginate, and the like, and any combination thereof. In various examples, the at least one polymeris chosen from polysilanes, poly siloxanes, polysulfides, polysilazanes, polyphosphazenes, and the like, and any combination thereof. In various examples, a polymer is or polymers are not a polymer or polymers than can melt electrospun (e.g., electrospun to provide a product).

[0085] In various examples, the materials comprise at least one first polymer and at least one second polymer. In various examples, the at least one first polymer is PGSP and / or the at least one second polymer PET.

[0086] In various examples, the at least one polymer has a concentration in the fluid stock(s) of about 5% to about 90% w / V, including all 0.1% w / V values and ranges therebetween. In various examples, the at least one polymer has a concentration in the fluid stock(s) of about 5% to 50% w / V, preferably from about 15% to about 40% w / V, or more preferably from about 20% to about 30% w / V, including all 0.1% w / V values and ranges therebetween.

[0087] The fluid stock(s) can be used to form fiber(s) comprising various material(s). In various examples, the material supply system is configured to deliver a single fluid stock or at least two fluid stocks from at least two reservoirs for at least one nozzle (such as, for example, delivering at least two fluid stocks into one nozzle or delivering different fluid stocks to different nozzles). In various examples, the fluid stock(s) comprising the at least one polymer is / are ejected from the nozzle(s) to form one or more fiber(s) comprising the at least one polymer. In various examples, at least one fluid stock comprises at least one first polymer and at least one second polymer, and / or where at least a first fluid stock comprises at least one first polymer and at least one second fluid stock comprises at least a second polymer. In various examples, the fluid stock(s) comprising the at least one first polymer and the at least one second polymer are ejected from the same or different nozzle(s) to form one or more fiber(s) comprising the at least one first polymer and / or the at least one second polymer.(0088] The fluid stock(s) can comprise various additive(s). In various examples, the fluid stock(s) further comprise(s) at least one additive. In various examples, the at least one additive is chosen from therapeutic agents, dyes, indicator agents, drugs, salts, and the like, and any combination thereof. In various examples, the at least one additive is dissolved in or dispersed as particles in the fluid stock(s).]0089] Fibrous product length is tunable with the instant methods and is considered to be only limited by the range of the motorized stage translating the spinneret. Fibrous product inner diameter and wall thickness are also tunable with this technique and can be varied along thelength of the conduit using mandrels of non-uniform diameters. Fiber thickness, fiber fusion, fiber stacking, and winding angle are also tunable and can be controlled by varying flow rate, applied voltage, spinneret translational speed mandrel rotation speed, or any combination thereof, along the length of the conduit and / or between translations of the spinnerets along the length of the conduit.(0090] The method can form a fibrous product comprising various morphological and / or structural feature(s). In various examples, the fibrous product has an inner diameter of about 0.5 mm to about 300 mm, including all 0.01 mm values and ranges therebetween, and / or an outer diameter of about 0.51 mm to about 300 mm, including all 0.01 mm values and ranges therebetween. In various examples, the average diameter of the fibers is from about 100 nm to about 500 microns including all 1 nm values and ranges therebetween.|0091| A method may be a static method. In various examples, the features of a static method (e.g., steps, components, conditions, parameters, or the like, any combination thereof) are substantially constant (or constant) during substantially all (or all) of the method (or method steps). A static method may be used to fabricate a fibrous product comprising one or more static layer(s). A method may be a dynamic method. In various examples, in a dynamic method, at least one of the features (e.g., step(s), component s), condition(s), parameter(s), or the like, any combination thereof) are altered during the method (e.g., during one or more or all of the steps). A dynamic method may be used to fabricate a fibrous product comprising one or more dynamic layer(s).

[0092] In various examples, the method further comprises one or more time(s) during formation of the fiber(s) one or more or all of the following: adding at least a third solvent to the fluid stock(s); altering the concentration of a conducting agent in the fluid stock(s); and, optionally, altering the electric potential(s) applied to the nozzle(s), where fiber fusion, fiber stacking, or a combination thereof is altered.

[0093] In various examples, the method further comprises one or more time(s) during formation of the fiber(s) one or more or all of the following: altering the translational speed of the nozzle(s); altering the flow rate per nozzle of the fluid stock through the nozzles; and altering the fiber collection speed of the collector system, where the winding angle and / or the diameter of the fiber(s) is altered. In various examples, the method further comprises one or more times during formation of the fiber(s) one or more or all of the following: altering the concentration ofone or more of the material(s) in the fluid stock(s); altering the concentration of one or more additive(s) in the fluid stock(s); and adding or removing fluid stock(s), where the composition of the fiber(s) is altered. In various example, a method further comprises one or more times during formation of the fiber(s) of each layer, independently, one or more or all of the following: altering the volume ratio of the at least one first solvent to the at least one second solvent in the fluid stock(s); adding at least a third solvent to the fluid stock(s); altering the concentration of a conducting agent in the fluid stock(s); and altering the electric potential(s) applied to the nozzle(s), if applied, altering spinneret translation, altering speed of collector rotation, or altering the winding angle and / or predetermined fiber pattern, or the like, where fiber fusion, fiber stacking, or a combination thereof is altered.

[0094] A method can be used to tune one or more propert(ies), such as, for example, compliance or the like, of a product, such as, for example, an arteriovenous graft or the like. In various examples, a method is a means to provide a product (such as, for example, an arteriovenous graft or the like) that exhibits desirable compliance. By selecting the material composition and / or one or more structural feature(s) of one or more or all the individual layers of a product (e.g., in the case of electrowritten layers, changing fiber composition (e.g., as described herein), winding angle (e.g., as described herein), average frequency of fusion points (e.g., as described herein), one or more system configurations(s) (such as, for example, altering the electric potential(s) applied to the nozzle(s), if applied, altering spinneret translation, altering speed of collector rotation, or the like, or any combination thereof), or the like, or any combination thereof) the compliance of a graft can be tuned (e.g., to a compliance of about 1 to about 80% / l 00 mmHg, including all 0. 1 % / l 00 mmHg values and ranges therebetween (e.g., about 5 % / 100 mmHg, about 10 % / l 00 mmHg, about 15% / l 00 mmHg, about 20% / 100 mmHg, about 25% / l 00 mmHg, about 30% / 100 mmHg, about 35% / l 00 mmHg, about 40 % / l 00 mmHg, about 45% / l 00 mmHg, about 50% / 100 mmHg, about 55% / l 00 mmHg, about 60% / 100 mmHg, about 65% / l 00 mmHg, about 70% / 100 mmHg, about 75% / l 00 mmHg, about 80% / 100 mmHg, or about 1 to about 20% / 100 mmHg). In various examples, a method provides a compliant product as described herein.

[0095] In an aspect, the present disclosure provides products. In various examples, a product is a multilayered product. In various examples, a product comprises (or is) a hybrid structure (e.g., comprising at least two different layers comprising different, such as, for example,structurally and / or compositionally different) materials). In various examples, a product is made using a system and / or by a method of the present disclosure. A product may be referred to, in the alternative, as a fibrous product. Non-limiting examples of products are provided herein.

[0096] A product can have various forms. Non-limiting examples of products include grafts (such as, for example, tissue grafts, vascular grafts (e.g., venous grafts, arterial grafts, arteriovenous grafts and the like), and the like), scaffolds, and the like).

[0097] In various examples, a product comprises a multilayer (e.g., hybrid structure) comprises a layer (e.g., an inner layer or core) comprising one or more porous elastomer(s) (e.g., at least a portion or all of which are porous biodegradable elastomer(s) or the like) (e.g., porous metalloelastomer(s), such as, for example, porous elastomer(s) independently comprise(s) one or more chelation crosslinked polymer(s), any one or all of which may be biodegradable, or the like) (e.g., an inner layer, a core or the like); and one or more layer(s) of fibers (e.g., electrowritten fibers, electrospun fibers, or the like, or any combination thereof) (e.g., an outer layer, a sheath or the like), where at least one of the layer(s) or one or more layer(s) are disposed on the layer comprising one or more porous elastomer(s) (e.g., at least a portion or all of which may be porous biodegradable elastomer(s) or the like) (e g., porous metalloelastomer(s), such as, for example, porous elastomer(s) independently comprise(s) one or more chelation crosslinked polymer(s), any one or all of which may be biodegradable, or the like) (e.g., an inner layer, a core or the like). In various examples, the fibers are arranged in a predetermined pattern; the average diameter of the fibers is from about 100 nm to about 500 microns; or the product comprises a desired fiber fusion and / or fiber stacking; or any combination thereof.

[0098] In various examples, product (e.g., a multilayer (e.g., hybrid structure)) comprises (or is) one or more electrowritten layer(s) (or electrospun layer(s)) (comprising a material or polymer(s) described herein) (e.g., an outer layer or sheath) or the like) and one or more layer(s) (e.g., an inner layer or core) formed using a conventional method (such as, for example, an electrospinning method, a templating method, or the like). In various examples, at least a portion or all of the one or more electro written layer(s) (or electrospun layer(s) or the like) (which may be referred to as a sheath) independently is / are at least partially or completely disposed (e.g., certain electrowritten layer(s) or electrospun layer(s) is / are in physical contact with or the like) on a layer or layers formed using a conventional method (which may be referred to as a core). Inthese examples, the independent electrowritten layer(s) (or electrospun layer(s) or the like) may be an exterior layer (such as, for example, a sheath or the like).|0099| A product may comprise a core and a sheath. In various examples, a core is a layer formed by a conventional method or system (such as, for example, an electrospinning method or system or the like) and a sheath, which may at least partially, substantially, or completely surround the core. In various examples, a sheath comprises one or more layer(s). In various examples, the sheath is a microfibrous sheath or a nanofibrous sheath. In various examples, a product (e.g., a graft (such as, for example, a tissue graft, a venous graft (e.g., an arteriovenous graft or the like), or the like), a scaffold, or the like) comprises a biodegradable core. In various examples, a product comprises a tubular core (which may be a biodegradable polyester tubular core), such as, for example, for a vascular graft or the like. It is contemplated that a disclosed product may include PGS or any biodegradable and / or biocompatible substance with similar degradation rates and elasticity of PGS. In some examples, a product further comprises a sheath (which may comprise one or more individual layer(s)) which surrounds the core (which may be an electrowritten (or electrospun or the like) biodegradable polyester tubular core, (which may comprise one or more individual layer(s))). In some examples, the sheath is a biodegradable polyester electrowritten (or electrospun) sheath which surrounds the tubular core to prevent, inhibit or reduce bleeding from such graft. In some examples, an electrowritten (or electrospun or the like) sheath (e.g., a biodegradable polyester sheath or the like) electrospun sheath comprises PCL or a PCL like substance which is capable of forming a less leaky (compared to a product without a sheath) or substantially nonleaky (or nonleaky) sheath, which may be hydrophobic, around the biodegradable polyester electrospun sheath. In some examples, the sheath includes a hemostatic material such as, for example, gelatin or the like, or any combination thereof, which is capable of inducing hemostasis shortly after implantation.

[0100] Without intending to be bound by any particular theory, it is considered that it can be desirable the inner layer (e.g., a porous elastomer or the like) degrades (e.g., biodegrades or the like) at faster (e.g., substantially faster) rate than the outer layer. In various examples, an inner layer (e.g., a porous elastomer or the like) degrades (e.g., biodegrades or the like) at a faster (e.g., substantially faster) rate than the outer layer.

[0101] A product (e.g., a multilayer (e.g., hybrid structure) product comprising an inner layer or core and / or an outer layer or sheath) can comprise various elelctrowritten layer(s) comprisingfibers. In various examples, the product comprises one or more layer(s) of fibers. A layer can comprise various fibers. In various examples, all of the layers in a product are the same. In various examples, at least one portion of a layer and / or at least one layer comprises fibers that have at least one feature (e.g., structural feature, geometrical feature, compositional feature, or the like) that is different than the fibers of the other portion(s) of the fibers in a layer or other fibers in a layer.

[0102] In various examples, a fiber is a microfiber or a nanofiber. In various examples, a product comprises two or more, or three or more layer(s), etc. of fibers. In various examples, the fibers are arranged in a predetermined pattern; the average diameter of the fibers is from about 100 nm to about 500 microns, including all 1 nm values and ranges therebetween; and the product comprises a desired fiber fusion and / or fiber stacking. In various examples, the average diameter of the fibers is from about 200 microns to at least 500 microns.[01031 The product can comprise various types and degrees of desired fiber fusion and / or fiber stacking. In various examples, the fibers (e.g., the fibers of a layer or individual layer) comprise a plurality of fusion points between two intersected fibers, such that for each fusion point, a bottom surface of a first fiber is bonded to a top surface of a second fiber. In various examples, for at least one or more or all fusion points, the overlapped distance of the first fiber and the second fiber is less than about 15%, less than about 10%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, or less than about 1% of the diameter of the first fiber and / or second fiber.

[0104] In various examples, the fibers (e.g., the fibers of a layer or individual layer) comprise an average frequency of fusion points from about 5% to about 99%, including all 1% values and ranges therebetween. In various examples, the fibers comprise an average frequency of fusion points of about 5% to about 99%, or from about 5% to about 90%, or from about 10% to about 60%, or at least about 5%, or at least about 7%, or at least about 10% , or at least about 15 %, or at least about 20%, or at least about 30%, or at most about 99 %, or at most about 90 %, or at most about 80%, or at most about 70 %, or at most about 60 %, or at most about 50%, including all 1% values and ranges therebetween.

[0105] In various examples, for each axial direction of the product, the adjacent fibers in different layers are aligned one over the other and are vertically stacked or vertically staggered.In various examples, the fibers have an average stacking height of at least about 10 microns, or atleast about 20 microns, or at least about 30 microns, or at least about 40 microns, or at least about 50 microns, or at least about 60 microns, or at least about 70 microns, or at least about 80 microns, or at least about 90 microns, or at least about 100 microns, or at least about 150 microns, or at least about 200 microns, or at least about 250 microns.

[0106] The product can comprise various predetermined patterns. In various examples, each layer (or individual layer of a layer comprising two or more individual layers) comprises one or more group(s) of fibers individually and optionally aligned in one or more axial direction(s) of the product within and / or between the layer(s). In various examples, the group(s) of fibers is / are independently uniaxially, biaxially, or multi-axially oriented within and / or between the layer(s). In various examples, each group of fibers has a substantially constant winding angle. In various examples, the winding angle is from about 1° to about 89°, including all 0.1° values and ranges therebetween. In various examples, the product comprises two groups of aligned fibers aligned in two directions with a substantially constant winding angle from about 15° to about 90°, from about 25° to about 80° or more preferably from about 35° to about 75°, including all 0.1° values and ranges therebetween, relative to the longitudinal axis of the product.

[0107] In various examples, two adjacent individual layers or two or more pairs of adjacent individual layers (e.g., of an outer layer or sheath) comprise different winding angles. In various examples, the difference between two adjacent individual layers or two or more pairs of adjacent individual layers (e.g., of an outer layer or sheath) is at least about 5% or more, at least about 10% or more, at least about 20% more, at least about 30% or more, or at least about 40% or more, at least about 50% or more (based on the larger winding angle). In various examples, the difference between two adjacent individual layers or two or more pairs of adjacent individual layers (e.g., of an outer layer or sheath) is about 5° to about 60 °, including all 0.1 ° values and ranges therebetween (e.g., about 10° or about 5° to about 20 °).

[0108] In various examples, the product comprises a plurality of pores. In various examples, the pores are defined by a plurality of fibers. In various examples, the pores are defined by a plurality of stacked fibers, a plurality of distributed fibers, or the like, or any combination thereof. For instance, a pore may be defined by a fiber of a first layer, spaced apart by a first predetermined space or pitch from the same fiber, or another fiber, on the first layer, and the fiber of a second layer, spaced apart by a second predetermined space or pitch, which may be equal to or different than the first predetermined space or pitch, with same fiber, or another fiber,on the second layer, with the fiber(s) of the first layer and the fiber(s) of the second layer being arranged at an angle relative to one another between 0° to 90°. In another example, a pore may be defined by fiber(s) of a first plurality of layers, spaced apart by a first predetermined space or pitch (which could comprise a varying space or pitch across the first plurality of layers) from the same fiber(s), or other fiber(s), comprising the first plurality of layers, and the fiber(s) of a second plurality of layers, spaced apart by a second predetermined space or pitch, which may be equal to or different than the first predetermined space or pitch (which could comprise a varying space or pitch across the second plurality of layers), with same fiber, or another fiber, on the second plurality of layers, with the fiber(s) of the first plurality of layers and the fiber(s) of the second plurality of layers being arranged at an angle relative to one another between 0° to 90°. (0109] In some examples, one or more pores are formed, by arrangement of fiber(s) across a thickness of the product, to extend through the product (e g., from an outer diameter to an inner diameter of a cylindrical product) or to extend only partially through a thickness of the product. In a substantially cylindrical product, for example, an axis of a pore may be described as extending from a first position (pi, (pi, zi) in a cylindrical coordinate system for the product to a second position (p2, cp2, Z2) in the cylindrical coordinate system wherein pi, epi and / or zi may be equal to, or different than, p2, q>2, Z2. Accordingly, in some examples, pores extend radially outwardly relative to a longitudinal axis of a substantially cylindrical product, whereas in some examples pores extend both outwardly relative to a longitudinal axis of a substantially cylindrical product and along the longitudinal axis and / or circumferentially.

[0110] In various examples, the average width of the pores is at least about 1 micron. In various examples, the average width of the pores is at least about 1 micron, at least about 5 microns, at least about 10 microns, at least about 20 microns, at least about 30 microns, at least about 40 microns, or at least about 50 microns. In various examples, the pores have a cube shape, a cuboid shape, a rhombohedron shape, a rhomboid shape, or the like.|01H| As used herein, the term “porosity” refers to the % by volume of pores based on the total volume of product. In various examples, the porosity of a product is 50% or greater, 55% or greater, 60% or greater, or 65% or greater. In various examples, the porosity of product is 50% or greater, 55% or greater, 60% or greater, 65% or greater, 70% or greater, 75% or greater, 80% or greater, 85% or greater, 90% or greater. In various examples, the porosity is an open pore structure. In various examples, the porosity is a closed pore structure. In various examples, theporosity is a continuous pore structure. In various examples, the pores are uniformly distributed. In various examples, the pores are non-uniformly distributed.I Oi l 21 A product can comprise fiber(s) comprising various material(s). In various examples, a product, such as, for example, a graft, which may be a venous graft, an arteriovenous graft, or the like, or the like, comprises an inner layer (or individual layers of an inner layer), such as, for example, a core, and / or an outer layer (or individual layers of an outer layer), such as, for example, a sheath) comprising fiber(s) comprising various material(s).

[0113] In various examples, at least a portion of the fibers or each fiber (e.g., of a layer or an individual layer) comprises one or more material(s) which is / are thermo-reactive at a temperature of at least 60 °C. In various examples, the one or more material(s) is / are thermo-reactive at a temperature of at least 60 °C, at least 100 °C, at least 150 °C, at least 166 °C, at least 170 °C, at least 180 °C, at least 190 °C, at least 200 °C, at least 210 °C, at least 220 °C, at least 230 °C, at least 240 °C, at least 250 °C, at least 260 °C, at least 270 °C, at least 280 °C, at least 290 °C, or at least 300 °C.(0114] In various examples, the one or more material(s) comprise(s) at least one polymer. In various examples, the one or more material(s) comprise at least two polymers. In various examples, the weight ratio of the two polymers is from about 1 :9 to about 9:1, from about 1 :5 to 5: 1, from about 1 :4 to about 4: 1, from about 1:3 to about 3: 1, from about 1 :2 to about 2:1, at least about 1 :99, about 1 :9, about 1 :8, about 1:7, about 1 :6, about 1 :5, about 1 :4, about 1 :3, about 1 :2, or about 1 : 1, or at most about 99: 1, at most about 9: 1, about 8: 1, about 7: 1, about 6: 1, about 5: 1, about 4: 1, about 3:1, about 2: 1, or about 1 : 1, including all integer weight ratio values and ranges therebetween.

[0115] In various examples, the at least one polymer comprises a cured (e.g., thermally cured, electromagnetic radiation cured, accelerated particle cured, or the like, or any combination thereof) polymer, or the like, or any combination thereof. In various examples, the at least one polymer does not comprise a cured (e.g., thermally cured, electromagnetic radiation cured, accelerated particle cured, or the like, or any combination thereof) polymer, or the like, or any combination thereof.

[0116] In various examples, the at least one polymer comprises a crosslinked (e.g., thermally crosslinked, electromagnetic radiation crosslinked, accelerated particle crosslinked, or the like, or any combination thereof) polymer, hydrogel, or the like, or any combination thereof. In variousexamples, the at least one polymer does not comprise a crosslinked (e.g., thermally crosslinked, electromagnetic radiation crosslinked, accelerated particle crosslinked, or the like, or any combination thereof) polymer, hydrogel, or the like, or any combination thereof.

[0117] In various examples, the at least one polymer comprises at least one biocompatible polymer, at least one biodegradable polymer, or the like, or any combination thereof. In various examples, the product comprises at least two biodegradable polymers, wherein a first biodegradable polymer has a degradation rate of at least 50% of the polymer degraded in less than about one year, less than about 9 months, less than about 6 months, less than about 3 months in a physiological environment or a biological environment; and a second biodegradable polymer has a degradation rate of at most about 50% of the polymer degraded in more than about one year, more than about 1.5 years, more than about 2 years, more than about 2.5 years, or more than about 3 years in a physiological environment or a biological environment.

[0118] In various examples, the at least one polymer is thermo-reactive at a temperature of at least about 60 °C. In various examples, the at least one polymer is thermo-reactive at a temperature of at least 60 °C, at least 100 °C, at least 150 °C, at least 166 °C, at least 170 °C, at least 180 °C, at least 190 °C, at least 200 °C, at least 210 °C, at least 220 °C, at least 230 °C, at least 240 °C, at least 250 °C, at least 260 °C, at least 270 °C, at least 280 °C, at least 290 °C, or at least 300 °C.

[0119] In various examples, the at least one polymer, is a synthetic organic polymer, a natural organic polymer, or an inorganic polymer. In various examples, the at least one polymer is chosen from a polyester, polyurethane, polyether, polyketal, polyamide, polyimide, polycarbonate, polyacrylate, polysaccharide, and any combination thereof. In various examples, the at least one polymer is chosen from polyglycolide or a polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone (PCL), polyhydroxyalkanoate (PHA), polyhydroxybutyrate (PHB), polyethylene adipate (PEA), polybutylene succinate (PBS), poly(3-hydroxybutyrate-co-3- hydroxy valerate) (PHBV), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyethylene glycol (PEG), polytrimethylene terephthalate(PTT), polyethylene naphthalate (PEN), poly(glycerol-sebacate) (PGS), palmitate functionalized poly(glycerol sebacate (PGSP), poly(epsilon caprolactone) (PCL), polymethyl methacrylate (PMMA), chitosan, gelatin, cellulose, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), polydioxanone, derivatives thereof, and the like, and any combination thereof. In various examples, the at least one polymeris chosen from silk, gelatin, and a polysaccharide, such as, for example, cellulose, chitin, chitosan, hyaluronic acid, dextran, and alginate, and the like, and any combination thereof. In various examples, the at least one polymer is chosen from polysilanes, polysiloxanes, polysulfides, polysilazanes, polyphosphazenes, and the like, and any combination thereof. In various examples, at least one fiber comprises at least one first polymer and at least one second polymer, and / or where at least one first fiber comprises at least one first polymer and at least second fiber comprises at least one second polymer. In various examples, the at least one first polymer is PGSP and / or the at least one second polymer is polyethylene terephthalate (PET).

[0120] In various examples, a layer or layers (e.g., a core, a sheath, or the like, individual layer(s) thereof, or at least a portion or all the individual fibers thereof, or a combination thereof) comprises one or more porous elastomer(s) (e.g., at least a portion or all of which may be porous biodegradable elastomer(s) or the like). In various examples, a layer or layers (e.g., a core) comprise(s) one or more porous chelation crosslinked polymer(s) or the like. In various examples, the sheath comprises PCL fibers. In various examples, the core comprises porous elastomer (e.g., a porous biodegradable elastomer or the like) and the sheath comprises PCL fibers.[0121| In various examples, a layer or layers (e.g., a core, a sheath, or the like, individual layer(s) thereof, or at least a portion or all the individual fibers thereof, or a combination thereof) comprise one or more chelation crosslinked polymer(s) and / or one or more polymer(s) suitable for chelation crosslinking (e.g., suitable for formation of chelation crosslinked polymer(s)), or the like, which may be porous, or any combination thereof.

[0122] In various examples, a layer or layers comprise one or more chelation crosslinked polymer(s) and / or one or more polymer(s) suitable for chelation crosslinking (e.g., suitable for formation of chelation crosslinked polymer(s)), or the like, or any combination thereof.

[0123] A chelation crosslinked polymer can comprise various structures. In various examples, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) is a chelation crosslinked oligomer, a chelation crosslinked prepolymer, a chelation crosslinked homopolymer, a chelation crosslinked copolymer, or the like, or a combination thereof. In various examples, a chelation crosslinked polymer is a chelation crosslinked polyester. In various examples, a chelation crosslinked polyester is a chelation crosslinked polyester oligomer, achelation crosslinked polyester prepolymer, a chelation crosslinked polyester homopolymer, a chelation crosslinked polyester copolymer, or the like, or a combination thereof.

[0124] In various examples, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) comprises a polymer backbone (e.g., a polyester backbone or the like) containing one or more repeat group(s) (e.g., ester group(s) or the like). In various examples, a chelation crosslinked polyester comprises a polyester backbone containing one or more ester group(s). In various examples, a polymer backbone (e.g., a polyester backbone or the like) comprises one or more chelation crosslinking group(s) within and / or pendant from the polymer backbone (e.g., the polyester backbone or the like). In various examples, a polyester backbone comprises one or more chelation crosslinking group(s) within and / or pendant from the polyester backbone.

[0125] In various examples, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) further comprises one or more cation(s). In various examples, a chelation crosslinked polyester further comprises one or more cation(s). In various examples, at least a portion of cation(s) is / are bonded to at least a portion of chelation crosslinking group(s). In various examples, said bonding thereby crosslinks the polymer backbone (e.g., a polyester backbone or the like). In various examples, said bonding thereby crosslinks a polyester backbone.

[0126] In various examples, a chelation crosslinked polyester comprises a polyester backbone comprising one or more ester group(s), wherein the polyester backbone comprises one or more chelation crosslinking group(s) within and / or pendant from the polyester backbone; and one or more cation(s), wherein at least a portion of the cation(s) is / are bonded to at least a portion of the chelation crosslinking group(s) via one or more chelation crosslinking bond(s), thereby crosslinking the polyester backbone. In various examples, 0.01 mol % to 50 mol % of the ester group(s) comprise a chelation crosslinking group.

[0127] In various examples, one or more (or all) chelation crosslinking group(s) is / are pendant from a polymer backbone (e.g., a polyester backbone or the like). In various examples, at least one or more or all of the chelation crosslinking group(s) is / are pendant from the polyester backbone.

[0128] In various examples, one or more repeat unit(s) (e.g., ester group(s) or the like) comprise(s) one or more chelation crosslinking group(s). In various examples, one or more estergroup(s) comprise(s) one or more chelation crosslinking group(s). Various mole ratios of chelation crosslinking group(s) to ester group(s) can be used. In various examples, 0.01 mol % to 100 mol % (e.g., 0.01 mol % to 50 mol %) of repeat group(s) (e.g., ester group(s) or the like), including all 0.01 mol % values and ranges therebetween, comprise a chelation crosslinking group. In various examples, 0.01 mol % to 100 mol % (e.g., 0.01 mol % to 50 mol %) of the ester group(s), including all 0.01 mol % values and ranges therebetween, comprise a chelation crosslinking group. In various examples, 0.01 mol % to 50 mol % of the ester group(s) comprise a chelation crosslinking group.

[0129] In various examples, the polymer backbone (e.g., a polyester backbone or the like) is an aliphatic polymer backbone (e.g., an aliphatic polyester backbone or the like) and one or more (or all) repeat group(s) (e.g., ester group(s) or the like) are aliphatic repeat group(s) (e g., aliphatic ester group(s) or the like). In various examples, the aliphatic repeat group(s) (e.g., ester group(s) or the like) of an aliphatic polymer backbone (e.g., an aliphatic polyester backbone or the like), comprise(s) one or more Ci to C20 alkyl group(s) (e.g., Ci, C2, C3, C4, Cs, Ce, C7, Cs, C9, C10, C11, C12, C13, C14, C15, Ci6, C17, Cis, C19, or C20 alkyl group(s), or the like, or combinations thereof). In various examples, the polyester backbone is an aliphatic polyester backbone, and wherein one or more or all of the ester group(s) is / are aliphatic ester group(s). In various examples, the aliphatic ester group(s) of an aliphatic polyester backbone comprise(s) one or more Ci to C20 alkyl group(s) (e.g., Ci, C2, C3, C4, C5, Ce, C7, Cs, C9, C10, C11, C12, C13, C14, C15, Cie, C17, Cis, C19, or C20 group(s), or the like, or combinations thereof).

[0130] A chelation crosslinked polymer can comprise various types of bonding between chelation crosslinking group(s) and cation(s). In various examples, at least a portion of (or all) cation(s) is / are bonded to at least a portion of (or all) chelation crosslinking group(s) via bonds chosen from ionic bonds, coordinate covalent bonds, and the like, and combinations thereof. In various examples, individual cation(s) is / are bonded to two or more chelation crosslinking group(s). In various examples, crosslinking is reversible. Various mole ratios of chelation crosslinking group(s) to cation(s) can be used. In various examples, the mole ratio of the chelation crosslinking group(s) to the cation(s) is 1 : 1 to 6: 1.

[0131] A chelation crosslinked polymer can comprise various other functional group(s). In various examples, a polymer backbone (e.g., a polyester backbone or the like) further comprises one or more other functional group(s) enabling one or more inter- and / or other intra-chainbond(s) other than chelation crosslinking bond(s). In various examples, a polyester backbone further comprises one or more functional group(s) enabling one or more inter- and / or intra-chain bond(s) other than chelation crosslinking bond(s). In various examples, functional group(s) are chosen from amide groups, carboxylate groups, hydroxyl groups, other hydrogen bonding functional groups (e.g., nucleic acid bases or the like), and functional group(s) capable of hostguest chemistry (e.g., cyclodextrin, adamantane or the like), and the like, and combinations thereof.

[0132] A chelation crosslinked polymer can comprise various other types of bonds other than chelation crosslinking bonds. In various examples, said inter- and / or other intra-chain bond(s) are chosen from hydrogen bonds, non-polar interactions, salt bridges, pi-pi bonds, and the like, and combinations thereof. In various examples, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) is crosslinked by said inter- and / or intra-chain bond(s)). In various examples, a chelation crosslinked polyester is crosslinked by said inter- and / or intra- chain bond(s). In various examples, said crosslinking is reversible. In various examples, one or more (or all) chelation crosslinking bond(s) and / or one or more (or all) other bond(s) is / are reversible. In various examples, one or more (or all) chelation crosslinking bond(s) and / or one or more (or all) other bond(s) is / are nonreversible.

[0133] In various examples, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) comprises a copolymer backbone (e.g., a polyester copolymer backbone or the like). In various examples, a chelation crosslinked polyester comprises a polyester copolymer backbone. Various copolymers backbones can be used. In various examples, a copolymer backbone is a block copolymer backbone comprising one or more other block(s) (other block(s) are block(s) other than polymer backbone blocks(s) (e.g., a polyester backbone block(s) or the like) chosen from one or more other hydrophilic block(s), one or more other hydrophobic block(s), and the like, and combinations thereof. In various examples, a polyester copolymer backbone comprises one or more other block(s) (other block(s) are block(s) other than polyester backbone block(s)) chosen from one or more other hydrophilic block(s), one or more other hydrophobic block(s), and the like, and combinations thereof.

[0134] In various examples, other hydrophilic block(s) is / are chosen from polyethylene glycol (PEG) blocks, polylactic acid (PLA) blocks, poly(acrylic acid) (PAA) blocks, and the like, and combinations thereof; and / or the hydrophobic block(s) is / are chosen from polyethyleneterephthalate (PET) blocks, poly(caprolactone) (PCL) blocks, poly(methyl methacrylate) (PMMA) blocks, and the like, and combinations thereof.|0135| A chelation crosslinked polymer can comprise various polymer backbones (e.g., polyester backbone(s) or the like) or copolymer backbone(s) (e.g., polyester copolymer backbone(s) or the like) structures. In various examples, a polymer backbone is a polyester backbone having the following homopolymer or copolymer structure:wherein R is a pendant chelation crosslinking group, m is 0.01 to 100 and n is 0 to 99.99. In various examples, all R groups are structurally the same. In various examples, one or more (or all) R groups are structurally different from one or more (or all) other R groups. In various examples, m is 0.01 to 100 (e.g., 0.01 to 50), including all 0.01 values and ranges therebetween, and n is 0 to 99.99 (e.g., 50 to 99.99), including all 0.01 values and ranges therebetween.

[0136] A chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) can comprise various chelation crosslinking group(s). In various examples, chelation crosslinking group(s) is / are chosen from polydentate chelation crosslinking groups, and the like, and combinations thereof. In various examples, chelation crosslinking group(s) is / are chosen from bidentate, tridentate, tetradendate, and pentadentate chelation crosslinking groups, and the like, and combinations thereof.

[0137] In various examples, a chelation crosslinking group comprises or a plurality of or all the chelation crosslinking groups each comprise one or more nitrogen donor group(s), one or more oxygen donor group(s), or the like, or a combination thereof. In various examples, chelation crosslinking group(s) is / are chosen from imine groups, carboxylate groups, aromatic heterocycle groups, amine groups, hydroxyl groups, ether groups, polyether groups, and crown ether groups, and the like, and combinations thereof. In various examples, chelation crosslinking group(s) is / are chosen from salicylaldimine groups, 2-vanillin groups, 2,3- dihydroxybenzaldehyde groups, 2,4-pyridinedicarbonyl dichloride groups, 2-[[3,4- bis[(triethylsilyl)oxy]phenyl]methyl]-oxirane groups, and [2,2'-Bipyridine]-5,5'-dicarbonyl dichloride groups, and the like, and combinations thereof.

[0138] A chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) may comprise one or more histidine group(s). In various examples, a histidine group is derived from (or formed from) a histidine amino acid.

[0139] A chelation crosslinked polymer can comprise various cation types and charges. In various examples, cation(s) is / are chosen from Group(II) cations, transition metals, and the like, and combinations thereof. In various examples, transition metals are chosen from first row transition metals, and the like, and combinations thereof. In various examples, cation(s) is / are present at 0.01% to 100% (e.g., 0.01% to 50%) by weight, including all 0.01 values and ranges therebetween, based on the total weight of a polymer backbone (e.g., a polyester backbone or the like) and cation(s).

[0140] A chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) can exhibit various properties. In various examples, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) exhibits one or more (or all) of the following: biocompatibility; biodegradability; a porosity of 60% or greater; a hysteresis of 100% or less; a contact angle of 53° to 83°; a strain of break of from 130% to 520%; a Young’s modulus of from 0.5 MPa to 4 MPa; an ultimate tensile strength (UTS) of from 1485 kPa to 2300 kPa; a water content of 0% to 50% by weight, based on the total weight of a polymer (e.g., a polyester or the like) and water. In various examples, a chelation crosslinked polyester exhibits one or more (or all) of the following: biocompatibility; biodegradability; a porosity of 60% or greater; a hysteresis of 100% or less; a contact angle of 53° to 83°; a strain of break of from 130% to 520%; a Young’s modulus of from 0.5 MPa to 4 MPa; an ultimate tensile strength (UTS) of from 1485 kPa to 2300 kPa; a water content of 0% to 50% by weight, based on the total weight of a polyester and water.

[0141] In various examples, a chelation polymer (e.g., a chelation polyester or the like) comprises a polymer backbone (e.g., a polyester backbone or the like) of the present disclosure but not one or more cation(s) of the present disclosure, thus crosslinking does not occur. In various examples, a chelation polymer comprises a polymer backbone (e.g., a polyester backbone or the like) and one or more cation(s) of the present disclosure, but the cation(s) is / are not bonded to the chelation crosslinking group(s), thus crosslinking does not occur.

[0142] In various examples, a chelation crosslinking polymer is a chelation crosslinking elastomer or the like. Non-limiting examples a chelation crosslinking elastomers includepoly(propanediol-co-(hydroxyphenylmethylene)aminopropanediol sebacate) (PAS), poly(l ,3- propanediol-co-(E)-N-(l,3-dihydroxypropan-2-yl)-3-(lH-imidazol-4 yl)acrylamide sebacate) (PPIAS), and the like, and any combination thereof.

[0143] In various examples, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) is not covalently crosslinked (e.g., does not comprise one or more covalent crosslinking bond(s)). In various examples, a chelation crosslinked polyester is not covalently crosslinked (e.g., does not comprise one or more covalent crosslinking bond(s)).

[0144] A polymer backbone (e g., a polyester backbone or the like) can exhibit various properties. In various examples, a polymer backbone (e.g., a polyester backbone or the like) exhibits a glass transition temperature (Tg) below room temperature. In various examples, a polymer backbone (e.g., a polyester backbone or the like) is semicrystalline. In various examples, a polyester backbone exhibits a glass transition temperature (Tg) below room temperature. In various examples, a polyester backbone is semicrystalline.[0145| A polymer backbone (e.g., a polyester backbone or the like) can comprise various molecular weight and / or poly dispersity index values. In various examples, a polymer backbone (e.g., a polyester backbone or the like) has a molecular weight (Mw and / or Mn) of 1,000 to 10,000,000 g / mol, including all 1 g / mol values and ranges therebetween, and / or a poly dispersity index of 1 to 5, including all 0.1 values and ranges therebetween. In various examples, a polyester backbone has a molecular weight (Mwand / or Mn) of 1,000 to 10,000,000 g / mol, including all 1 g / mol values and ranges therebetween, and / or a poly dispersity index of 1 to 5, including all 0.1 values and ranges therebetween.

[0146] In various examples, a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like) may comprise one or more functional group(s) (e.g., hydroxyl group(s), carboxylic acid group(s), or the like, or a combination thereof) located, e.g., in end group(s), chelation crosslinking group(s), polymer backbone group(s), or the like, which can provide sites to which molecules may be attached to modify the bulk or surface properties of the polymer (Jayachandran, K. N., et al., Synthesis of Dense Brush Polymers with Cleavable Grafts. Eur. Polym. J. 36: 743-749, 2000; Laschewsky, A., et al, Tailoring of Stimuli-responsive Water Soluble Acrylamide and Methacrylamide Polymers. Macromol. Chem. Phys. 202: 276-286, 2001).

[0147] For example, tert-butyl, benzyl, or other hydrophobic groups may be added to a a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like) to reduce the degradation rate of the polymer. Polar organic groups such as, for example, methoxy groups and the like, may also facilitate adjustment of both the degradation rate and hydrophilicity. In contrast, addition of hydrophilic groups, for example, sugars and the like, at these sites may increase the degradation rate. Acid groups may also be added to a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like), to modify one or more propert(ies) of the polymer. For example, molecules with carboxylic or phosphoric acid groups or acidic sugars or the like may be added. Charged groups such as, for example, sulfates, amines, and the like may also be attached to a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like). Groups that are added to a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like)may be added via linkage to a functional group (e.g., a carboxylate groups or a carboxylic acid group or a hydroxyl group (substituting for hydrogen) or the like), linked directly to the backbone of a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like), incorporated into an organic group which is linked to a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like), or the like. For example, a charged amino acid such as, for example, arginine, histidine, or the like may be attached to modify the degradation rate.

[0148] Attachment of such non-protein organic or inorganic groups modifies the hydrophilicity and the degradation rate and mechanism of a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like). Protecting group chemistry may also be used to modify the hydrophilicity of a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like). One skilled in the art will recognize that a wide variety of non-protein organic and inorganic groups may be added to or substituted for the functional groups in a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like) to modify its properties. Exemplary functional groups are also described in March, Advanced Organic Chemistry. Fifth edition, John Wiley & Sons, Inc., New York, 1995, thecontents of which with regard to functional groups and related chemistry are incorporated by reference herein.|0149| To further control or regulate interaction of a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like) with cells, biomolecules, small molecules, bioactive agents, or the like may be coupled to the functional groups or otherwise integrated into the polymer backbone or chelation crosslinking group(s) of a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) (Barrera, D., et al., Synthesis and RGD Peptide Modification of a New Biodegradable Copolymer: Poly(lactic acid-co-lysine). J. Am. Chem. Soc. 115: 11010-11, 1993; West, J. L., et al., Polymeric Biomaterials with Degradation Sites for Proteases Involved in Cell Migration. Macromolecules 32: 241-244, 1999; Mann, B. K., Smooth Muscle Cell Growth in Photopolymerized Hydrogels with Cell Adhesive and Proteolytically Degradable Domains: Synthetic ECM Analogs for Tissue Engineering. Biomaterials 22, 3045-3051; 2001).Biomolecules, small molecules, bioactive agents, or the like, or a combination thereof which are encapsulated within a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like), perhaps linked to it using non-covalent interactions, but not attached to the a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like) may diffuse out of a polymer prior to degradation of a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like). In contrast, attachment of biomolecules, small molecules, bioactive agents, or the like to a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like) may result in a slower release rate because biomolecules, small molecules, or bioactive agents may not be released from the material until it degrades.

[0150] In various examples, biomolecules, such as, for example, growth factors may be exploited to recruit cells to a wound site or promote specific metabolic or proliferative behavior in cells that are at the site or seeded within the matrix. Exemplary growth factors include, but are not limited to, TGF-P, acidic fibroblast growth factor, basic fibroblast growth factor, epidermal growth factor, IGF-I and II, vascular endothelial-derived growth factor, bone morphogenetic proteins, platelet-derived growth factor, heparin-binding growth factor, hematopoetic growth factor, peptide growth factor, and the like. Integrins and cell adhesion sequences (e.g., the RGDsequence and the like) may be attached to the chelation crosslinked polymers (e.g., chelation crosslinked polyesters, or the like) to facilitate cell adhesion. Integrins are part of a large family of cell adhesion receptors that are involved in cell-extracellular matrix and cell-cell interactions. The RGD sequence, present in proteins such as, for example, fibronectin and the like, has been shown to be active in promoting cell adhesion and proliferation (Massia, et al., J. Cell. Biol. 114: 1089, 1991). Extracellular matrix components, e.g., collagen, fibronectin, laminin, elastin, etc., may be combined with a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) to manipulate cell recruitment, migration, metabolism, or the like or a combination thereof and / or the degradation properties, mechanical properties or the like, or a combination thereof of the material. Proteoglycans and glycosaminoglycans may also be covalently or non-covalently attached to a polymer (such as, for example, a chelation crosslinked polymer (e.g., a chelation crosslinked polyester or the like) or the like).[01511 In various examples, at least one fiber further comprises at least one additive. In various examples, the additive is uniformly distributed in at least one fiber and / or encapsulated by or attached to the polymer(s) in at least one fiber. In various examples, the at least one additive is chosen from a therapeutic agent, a dye, an indicator agent, a drug, and the like, and any combination thereof. In various examples, the additive is a therapeutic agent or a drug, configured to gradually deliver to a physiological environment after implanting the product into the physiological environment.[0152[ A layer or layers (e.g., of an inner layer or core) formed using conventional methods are known in the art. In various examples, a layer or layers formed using conventional methods is / are a layer or layers comprising a material described in, a layer or layers described in, or a layer or layers made by a method described in, or any combination thereof, International Patent Application No. PCT / US2021 / 044230, fded August 2, 2021 and titled “Chelation Crosslinked Polymers, Methods of Making Same, and Uses Thereof’, the disclosure of which with regard to material (such as, for example, chelation crosslinked polymers and the like) and methods of making same and uses of same are incorporated herein by reference.[0153) The product can comprise various morphological and / or structural feature(s). In various examples, the product has an inner diameter of about 0.5 mm to about 300 mm, including all 0.01 mm values and ranges therebetween, and / or an outer diameter of about 0.51 mm to about 300 mm, including all 0.01 mm values and ranges therebetween. In variousexamples, the product is a conduit, a web, a patch, a mat, a cuff, or the like. In various examples, the product comprises a shape of at least a portion of an organ, a vessel, a body part, or the like. In various examples, the product is a conduit, a web, a patch, a mat, or a cuff, comprising a shape of at least a portion of an organ, a vessel, a body part, or the like.

[0154] A product may be asymmetric. In various examples, a product is asymmetric in terms of one or more dimension(s), one or more mechanical propert(ies), fiber composition, or fiber structure (e.g., fiber fusion, fiber stacking, pore shape, pore size, or the like), or any combination thereof. In various examples, product asymmetry is in terms of fiber alignment, fiber orientation, winding angle, or the like. As an illustrative example, one or more of the aforementioned features of a product (such as, for example, a conduit or the like) is altered from an end (e.g., an orifice) to another end (e.g., another orifice). In various examples, an asymmetric product is a scaffold or graft, which may be used as an artificial trachea, artificial bronchia, a vascular graft (such as, for example, a venous graft, an arterial graft, an arteriovenous graft, or the like) or the like.

[0155] A vascular graft (such as, for example, a venous graft, an arterial graft, or an arteriovenous graft, or the like) may be asymmetric. In various examples, an arteriovenous graft is asymmetric in terms of orifice or end size (e.g., linear inner dimension, such as, for example, a diameter or the like), orifice or end wall thickness, or the like. In various examples, an arteriovenous graft accommodates the size “mismatch” between arteries and veins (arteries are typically smaller in diameter but with thicker wall) for both conduit diameter and wall thickness. In various examples, an arteriovenous graft comprises a first end (which may be a venous end) that is wider (e.g., has a larger inner diameter) and / or is thinner (e.g., has a smaller wall thickness) than a second end (which may be an arterial end) and or a second end (which may be an arterial end) that is narrower (e.g., has a smaller inner diameter) and / or is thicker (e.g., has a larger wall thickness) than a first end (which may be an venous end).|0156| A vascular graft (such as, for example, a venous graft, an arterial graft, or an arteriovenous graft, or the like) may exhibit desired compliance (such as, for example, axial compliance and / or radial compliance) and / or suture retention. In various examples, compliance is the ability of a product, such as, for example, a vascular graft (e.g., a venous graft, an arterial graft, or an arteriovenous graft, or the like), to change its dimension or diameter in the case of a tube, in response to the pressure it is subjected to (such as, for example, the blood pressure in anindividual or the like). Without intending to be bound by any particular theory, it is considered a vascular graft (such as, for example, a venous graft, an arterial graft, or an arteriovenous graft, or the like) may be a compliant vascular graft (such as, for example, a compliant venous graft, a compliant arterial graft, or a compliant arteriovenous graft, or the like). In various examples, at least a portion, substantially all, or all of vascular graft (such as, for example, a venous graft, an arterial graft, or an arteriovenous graft, or the like) or the like exhibits a radial compliance of about 1 to about 80% / 100 mmHg, including all 0.1 % / l 00 mmHg values and ranges therebetween (e.g., 5 % / 100 mmHg, 10 % / 100 mmHg, 15% / 100 mmHg, 20% / 100 mmHg, 25% / l 00 mmHg, 30% / l 00 mmHg, 35% / l 00 mmHg, 40 % / 100 mmHg, 45% / l 00 mmHg, 50% / 100 mmHg, 55% / l 00 mmHg, 60% / 100 mmHg, 65% / l 00 mmHg, 70% / 100 mmHg, 75% / 100 mmHg, or 80% / 100 mmHg). In various examples, a first portion of a vascular graft (such as, for example, a venous graft, an arterial graft, or an arteriovenous graft, or the like) or a portion thereof exhibits radial compliance (such as, for example, arterial radial compliance or the like) of about 3 to about 15% / 100mmHg, including all 0.1% / 100mmHg values and ranges therebetween (e.g., about 5 to about 15% / lOOmmHg) and / or a second portion of a vascular graft (such as, for example, a venous graft, an arterial graft, or an arteriovenous graft, or the like) exhibits radial compliance (such as, for example, venous compliance) of about 45 to about 60% / 100mmHg, including all 0.1% / 100mmHg values and ranges therebetween (e.g., 50 to about 60% / 100mmHg). In various examples, an arteriovenous graft (e.g., at least a portion of an arteriovenous graft comprising a second end (which may be an arterial end)) exhibits arterial radial compliance (such as, for example, arterial radial compliance) of about 3 to about 15% / 100mmHg, including all 0.1% / 100mmHg values and ranges therebetween (e.g., about 5 to about 15% / lOOmmHg) and / or an arteriovenous graft (e.g., at least a portion of an arteriovenous graft comprising a first end (which may be a venous end)) exhibits venous radial compliance (such as, for example, venous compliance) of about 45 to about 60% / 100mmHg, including all 0.1% / lOOmmHg values and ranges therebetween (e.g., 50 to about 60% / 100mmHg).

[0157] In various examples, a product (such as, for example, a vascular graft (e.g., a venous graft, an arterial graft, or an arteriovenous graft, or the like) exhibits varying compliance along a longest linear axis (such, as, for example, a longitudinal axis or the like) of the product. In various examples, compliance varies linearly or non-linearly and / or continuously or discontinuously along a longest linear axis (such, as, for example, a longitudinal axis or the like)of the product. In various examples, compliance is greater at a second end or proximate to a second end of a vascular graft (such as, for example, a venous end of an arteriovenous graft or the like) relative to the compliance at or proximate to a first end of a vascular graft (such as, for example, an arterial end of the arteriovenous graft or the like). In various examples, compliance is at least about 4 times, at least about 5 times, at least about 6 times, at least about 7 times, at least about 8 times greater or about 4 times to about 8 times, including all 0.1 times values and ranges therebetween, greater at a second end or proximate to a second end (which may be a venous end) of an arteriovenous graft relative to the compliance at or proximate to a first end (which may be an arterial end) of the arteriovenous graft. In various examples, compliance is about 45 to about 60% / 100mmHg, including all 0.1% / 100mmHg values and ranges therebetween (e.g., about 50 to about 60% / 100mmHg) at a second end or proximate to a second end of a vascular graft (such as, for example, a venous end of an arteriovenous graft or the like) and / or about 3 to about 15% / 100mmHg, including all 0.1% / 100mmHg values and ranges therebetween (e.g., about 5 to about % / 100mmHg) at a first end or proximate to a first end of a venous graft (such as, for example, an arterial end of the arteriovenous graft or the like).

[0158] In various examples, a product (such as, for example, a vascular graft (e.g., a venous graft, an arterial graft, or an arteriovenous graft, or the like) (which may be a compliant product) comprises one or more layer(s) of fibers (such as, for example, layer(s) independently comprising electrowritten fibers (which may be an outer layer, a sheath, or the like). In various examples, the electrowritten fibers of an individual layer comprise one or more polymer(s) (e.g., as described herein), a winding angle (e.g., as described herein), degree of fiber fusion (e.g., as described herein), or the like, or any combination thereof. In various examples, a product (such as, for example, a vascular graft (e.g., a venous graft, an arterial graft, or an arteriovenous graft, or the like) (which may be a compliant product) exhibits a compliance as described herein.

[0159] In various examples, a product (such as, for example, a vascular graft (e.g., a venous graft, an arterial graft, or an arteriovenous graft, or the like) (which may be a compliant product) comprises one or more layer(s) of fibers (such as, for example, layer(s) independently comprising electrowritten fibers (which may be an outer layer, a sheath, or the like) that make up about 1% to about 50%, including all 0.1% values and ranges therebetween (e.g., about 1 to about 5%, about 1 to about 10%, about 11 to about 20%, about 21 to about 30%, about 31 to about 40%, about 41 to about 50%) of the total amount of the arteriovenous graft material (byweight). In various examples, the layer(s) independently comprise fibers with a winding angle of about 10to about 89°, including all 0.1° values and ranges therebetween (e.g., about 55° to about 89°) and / or average frequency of fusion points about 5 to about 99% (e.g., about 10%, about 15%, about 20%, about 25%, about 30%, about 40%, about 50%>, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%). In various examples, an arteriovenous graft (which may be a compliant arteriovenous graft) exhibits a compliance as described herein.|0160| In various examples, a product is an autologous and / or hemocompatible vascular conduit or the like. In various examples, a product is an autologous and / or hemocompatible vascular graft or the like. Non-limiting examples of autologous and / or hemocompatible vascular grafts include autologous and / or hemocompatible venous grafts, autologous and / or hemocompatible arterial grafts, and autologous and / or hemocompatible arteriovenous grafts, and the like, and any combination thereof.

[0161] The product can have various medical applications, pharmaceutical applications, industrial applications, or the like, or any combination thereof. In various examples, the product can be used for thermal insulation, for gas or liquid filtration, as a membrane, as a fabric, as a composite material, or the like.

[0162] The product can be used for various medical applications. In various examples, the product is an implantable medical device, a scaffold of an artificial tissue, or the like. In various examples, a product is a sheet, tube, mesh, pseudo 3-dimensional construct, or the like.

[0163] The shape of a product may also be manipulated for specific tissue engineering applications. Exemplary shapes include, but are not limited to, particles, tubes, spheres, strands, coiled strands, films, sheets, fibers, meshes, foams, and the like, and any combination thereof. In various examples, a product has high porosity, low porosity, or a combination of different porosities. In some examples, the constructs are vascularized (micro-channeled) fibrous sheets, random meshes, aligned sheets, cylindrical tubes, or pseudo 3 -dimensional constructs, such as, for example, shapes to mimic organs or the like. These structures are particularly useful for applications in soft and elastomeric tissues.

[0014] In various examples, a product, which may be a solution electrowritten product or the like, is a graft (such as, for example, a tissue graft, a vascular graft (e.g., a venous graft, an arterial graft, an arteriovenous graft, or the like), or the like), a scaffold (such as, for example, atissue engineering scaffold or the like), or the like. In various examples, a graft or a scaffold (e g., prior to use, such as, for example, implantation or the like) is substantially cell-free or cell free.

[0165] In various examples, a product is used for the replacement and / or repair of damaged native tissues. In various examples, a scaffold is used in in situ tissue engineering applications, including, but not limited to, vascular grafts, bone, intestine, liver, lung, or any tissue with sufficient progenitor / stem cells. In various examples, a product is useful for regenerating tissues that are subject to repeated tensile, hydrostatic, or other stresses, such as, for example, lung, blood vessels, heart valve, bladder, cartilage, muscle, and the like. For example, a product is contemplated to be implantable for tensile load bearing applications, such as, for example, tubular networks with a finite number of inlets and outlets, tubes configured to act as artery interpositional grafts, and the like.

[0166] A product may be contacted (e g., seeded or the like) with cells or implanted directly and relying on the host to serve as cell source and "bioreactor". These structures can be implanted as artificial organs and the inlets and outlets will be connected to host tissues, vasculature, or the like. In some examples, the vasculature itself is valuable without parenchymal cells. For example, in treating ischemic diseases. The microvascular mimetics can be connected directly to a host vessel and perfuse an ischemic area of the body. In some examples, a product, such as, for example, a vascular graft (e.g., a venous graft, an arterial graft, or the like) or the like, is cell-free, in which it does not include any living cells, such as, for example, smooth muscle cells, endothelial cells, or the like, or any combination thereof.

[0167] Without intending to be bound by any particular theory, it is considered that a product can guide host tissue remodeling in many different tissues, including any tissue that has progenitor cells. For example, a biodegradable scaffold is used to facilitate tissue regeneration in vivo by providing a structural frame for which tissue regeneration can occur. In some examples, a product allows and facilitates infdtration of host cells, including progenitor cells and the like. In some examples, a product allows and facilitates host remodeling of the biodegradable structure, so that the polymeric structure is replaced by the desirable host tissue. It is contemplated that the methods of fabrication and / or systems disclosed herein can be modified as desired by one of ordinary skill in the art to fabricate a product with the appropriate dimensions and features depending upon tissue which is to be replaced.

[0168] The various dimensions of a product can vary according to the desired use. In principle, the dimensions will be similar to those of the host tissue in which the scaffold / graft is being used to replace. For example, in the case of a vascular graft, a vascular graft has an inner diameter which matches that of the host vessel to be replaced. However, it is contemplated the graft wall can be fabricated with a thicker or thinner wall than that which is being replaced, if desired. Typically, the wall thickness of a disclosed scaffold or vascular graft is designed to match that of the host tissue or vessel to be replaced.

[0169] In various examples, a product (e.g., a tissue graft) is a soft tissue graft or the like. In various examples, a tissue graft is a soft tissue graft (such as, for example, blood vessel grafts, muscle grafts, skin grafts, ligament grafts, internal organs (such as, for example, lungs, kidneys, hearts or the like), nervous system tissue grafts or the like), or the like. In various examples, a soft tissue graft is a vascular graft or the like. In various examples, a vascular graft is a venous graft, an arterial graft, an arteriovenous graft, or the like. In various examples, an arterial graft comprises a lumen diameter of about 6 mm or less.

[0170] In some examples, a vascular graft is used to form a blood vessel in vivo. For example, a vascular graft can be implanted into an individual in need of vascular graft at the desired location to form a conduit in which blood can initial flow and ultimately form a blood vessel. In various examples, a vascular graft is used as a coronary or a peripheral arterial graft, venous grafts, lymphatic vessels, or the like. In some examples, a vascular graft is used as an arteriovenous shunt for dialysis access (e g., where “maturation” of 2-3 months is common). [0.1.71] In various examples, a product is biodegradable and / or biocompatible. In some examples, a disclosed scaffold includes PGS and / or one or more of the following polymers: polylactides (PLAs), poly(lactide-co-glycolides) (PLGAs), poly(dioxanone), polyphosphazenes, polyphosphoesters (such as, poly[l,4-bis(hydroxyethyl)terephthalate-alt-ethyloxyphosphate]; poly[l,4-bis(hydroxyethyl)terephthalate-alt-ethyloxyphosphate]-co-l,4- bis(hydroxyethyl)terephthalate-co-terephthalate; poly[(lactide-co-ethylene glycol)-co- ethyloxyphosphate]); polycaprolactone; poly(urethanes), polyglycolides (PGA) polyanhydrides, and polyorthoesters or any other similar synthetic polymers that may be developed that are biologically compatible.

[0172] The term “biologically compatible, synthetic polymers” includes copolymers and blends, and any other combinations of the forgoing either together or with other polymersgenerally. The use of these polymers will depend on given applications and specifications required. A more detailed discussion of these polymers and types of polymers is set forth in Brannon-Peppas, Lisa, “Polymers in Controlled Drug Delivery,” Medical Plastics and Biomaterials, November 1997, the disclosure of which with regard to biologically compatible and / or synthetic polymers is incorporated by reference.(0173] In some examples, a product comprises pores to facilitate cell infiltration, but pores are not necessarily required. In some examples, the pores are uniformly distributed. In some examples, the pores are non-uniformly distributed.

[0174] In some examples, a product comprises uniformly distributed pores. In some examples, a product comprises non-uniformly distributed pores. In some examples, product does not include any pores. In some examples, a porous product comprises at least 75% pore interconnectivity, such as, for example, about 80% to about 90%, about 90% to about 98%, including about 75%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 99.5%, or about 99.99% interconnectivity.|0175| At least a portion or all of a product may degrade after implantation in an individual. In some examples, at least 50%, such as, for example, about 55% to about 70%, about 80% to about 90%, about 90% to about 98%, including about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, about 99.5%, or about 99.99% of a scaffold or tissue graft (e.g., a vascular graft) degrades within one year, such as, for example, within about 1 to about 10 months, including within 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, or about 12 months of implantation.|0176] In some examples, a product is coated with a biocompatible and / or biodegradable material. It is contemplated that one of ordinary skill in the art can determine with but limitedexperimentation, which substrates are suitable for a particular application. In some examples, the inner luminal surface of the product is coated with a biocompatible and / or biodegradable material. It is contemplated that such coating may be complete or partial. In some examples, the inner luminal surface of a product is coated completely with a thromboresistant agent, such as, for example, heparin and / or other compounds known to one of skill in the art to have similar anti-coagulant properties as heparin, to prevent, inhibit or reduce clotting within the inner lumen of the vascular graft.

[0177] In some examples, a product is impregnated with any of a variety of agents, such as, for example, suitable growth factors, stem cell factor (SCF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), cartilage growth factor (CGF), nerve growth factor (NGF), hepatocyte growth factor (HGF), stromal cell derived factor (SDF), platelet derived growth factor (PDGF), keratinocyte growth factor (KGF), skeletal growth factor (SGF), osteoblast-derived growth factor (BDGF), insulin-like growth factor (IGF), cytokine growth factor (CGF), stem cell factor (SCF), colony stimulating factor (CSF), growth differentiation factor (GDF), integrin modulating factor (IMF), calmodulin (CaM), thymidine kinase (TK), tumor necrosis factor (TNF), growth hormone (GH), bone morphogenic proteins (BMP), interferon, interleukins, cytokines, integrin, collagen, elastin, fibrillins, fibronectin, laminin, glycosaminoglycans, heparan sulfate, chondrotin sulfate (CS), hyaluronic acid (HA), vitronectin, proteoglycans, transferrin, cytotactin, tenascin, and lymphokines.[0.1.78] In some particular examples, a product comprising a solution electrospun biodegradable polyester core and an electrospun biodegradable polyester electrospun outer sheath surrounding the biodegradable polyester core with or without a thromboresistant agent coating the biodegradable scaffold is used to facilitate tissue regeneration in vivo by providing a structural frame for which tissue regeneration can occur.

[0179] In some examples, a product comprises one or more natural polymer(s) including, but are not limited to amino acids, peptides, denatured peptides such as, for example, a gelatin from denatured collagen, polypeptides, proteins, carbohydrates, lipids, nucleic acids, glycoproteins, minerals, lipoproteins, glycolipids, glycosaminoglycans, proteoglycans, and the like, and any combination thereof. In certain examples, collagen is included. In certain examples, collagen is excluded. In certain cases, non-living macromolecular structures derived from biological tissuesincluding, but are not limited to skins, vessels, intestines, internal organs, can be used alone or in combination with synthetic polymers named above.|0180| A vascular graft may be an arteriovenous graft. In various examples, an arteriovenous graft is used to connect a vein and an artery. In various examples, an arteriovenous graft is used for hemodialysis access. An arteriovenous graft may be symmetric or asymmetric.

[0181] An arterio-venous (AV) graft can have various regions. In various examples, an AV graft comprises a venous zone, a transition zone, and an arterial zone. In various examples, the AV graft comprises a first end (e.g., a venous end) or a first orifice (e.g., a venous orifice) in the venous zone. In various examples, the AV graft comprises a second end (e.g., arterial end) or a second orifice (e.g., an arterial orifice) in the arterial zone. In various examples, an AV graft comprises a transition zone between the first and second ends or orifices. In various examples, an AV graft comprises gradually decreasing diameter accompanied by increasing wall thickness moving along the transition zone from the first to the second end or orifice.

[0182] In various examples, an arteriovenous graft comprises an inner diameter of about 3 to about 20 mm, including all 0.01 mm values and ranges therebetween, at an end (which may be a first end, venous end or wide end) to about 2 to about 10 mm, including all 0.01 mm values and ranges therebetween, at the other end (which may a second end, opposite end, arterial end, or a narrow end) of the graft. In various examples, an arteriovenous graft includes two orifices. In various examples, an arteriovenous graft includes a first orifice (e.g., a venous orifice) and a second orifice (e g., an arterial orifice). In various examples, the wall thickness of the first orifice (e.g., venous orifice) is from about 0.05 to about 4 mm (e.g., from about 0.05 to about 3 mm), including all 0.01 mm values and ranges therebetween, and / or the wall thickness of the second orifice (e.g., arterial orifice) is from about 0.2 to about 5 mm, including all 0.01 mm values and ranges therebetween. The first orifice (e.g., venous orifice) may be configured to be fluidly connected with a vein of an individual. The second orifice (e.g., arterial orifice) may be configured to be fluidly connected with an artery of an individual.

[0183] In various examples, an arteriovenous graft is asymmetric in terms of orifice or end size (e.g., linear inner dimension, such as, for example, a diameter or the like), orifice or end wall thickness, or the like. In various examples, an arteriovenous graft accommodates the size “mismatch” between arteries and veins (arteries are typically smaller in diameter but with a thicker wall) for both conduit diameter and wall thickness. In various examples, an arteriovenousgraft comprises a first end (which may be a venous end) that is wider (e.g., has a larger inner diameter) and / or is thinner (e.g., has a thinner wall thickness) than a second end (which may be an arterial end). Without intending to be bound by any particular theory, it is considered that the difference in hardness and / or stiffness results from the first end (which may be a venous end) being wider and / or thinner than the second end (which may be an arterial end). Arteries and veins also have different composition and organization, further contributing to the difference in biomechanics. Non-limiting examples of arteriovenous grafts are described herein. In various examples, an arteriovenous graft comprises a tapered inner diameter.

[0184] In various examples, the ratio of a first end (e.g., venous end) inner diameter to a second end (e.g., arterial end) inner diameter is from about 1.5: 1 to about 10:1 (e.g., from about 1.5: 1 to about 8: 1), including all 0.1 values and ranges therebetween, and / or the ratio of first end (e.g., venous end) wall thickness to second end wall thickness is from about 1 : 1.25 to about 1 : 100 (e.g., from about 1 :4 to about 1 : 10), including all 0.1 values and ranges therebetween. In various examples, the second end (which may be an arterial end) of the arteriovenous graft is harder and / or stiffer than the first end (which may be a venous end).

[0185] In various examples, an inner linear dimension of the first orifice (e.g., venous orifice), which may be an inner diameter of the first orifice, is from about 10% to about 1000% larger (e.g., from about 10% to about 200% larger), including all 0.1 % values and ranges therebetween) than an inner linear dimension of the second orifice (e.g., arterial orifice), which may be an inner diameter of the second orifice. In various examples, a linear dimension of the first orifice (e.g., venous orifice), which may be a wall thickness of the first orifice, is from about 5% to about 10,000% smaller, including all 0.1 % values and ranges therebetween, than a linear dimension of the second orifice (e.g., arterial orifice), which may be a wall thickness of the second orifice.

[0186] An arteriovenous graft can be used in a hemodialysis method. In various examples, a hemodialysis method comprises implanting an arteriovenous graft in an individual and subsequently carrying out hemodialysis on the individual. In various examples, the implanting comprises fluidly connecting (e.g., by suturing or the like) a first orifice (e.g., venous orifice) to a vein of an individual and / or fluidly connecting (e.g., by suturing or the like) a second orifice (e.g., arterial orifice) to an artery of the individual.

[0187] An individual may be a human or non-human mammal or other animal. Non-limiting examples of non-human animals or mammals include cows, pigs, goats, mice, rats, rabbits, cats, dogs, or other agricultural mammals, pet, or service animals, and the like.

[0188] The following Statements describe various examples of systems, methods, and products of the present disclosure and are not intended to be in any way limiting:Statement 1. A solution electrowriting system comprising: one or more nozzle(s) (e.g., one spinneret or a plurality of spinnerets); a material supply system comprising one or more contained s) / reservoir(s) (e.g., Syringe, Pump, mixing chamber, or syringe pump) fluidically coupled to the one or more nozzles and configured to supply one or more fluid stock(s) (e.g., a solution, or at least two solutions from at least two pumps for at least one nozzle (such as, for example, mixing solutions into one nozzle, or different solutions for different nozzles); a collector system (e.g., a collecting substrate, a collector, collector system, or mandrel, Modular Rotating Collector System) configured to collecting fiber(s) emanating / injecting from the one or more nozzle(s); and, optionally, one or more power source(s) (e.g., a High Voltage Power Supply) configured to provide one or more electric potential(s) (e.g., one or more voltage) to / between the collector and (each of) the nozzle(s) (e.g., spinneret(s)); where the fluid stock is / comprises a solution comprising at least one solvent (e.g., a first solvent) or at least two solvents (e.g., a first solvent and a second solvent), and at least one material (e.g., at least one polymer) configured to form at least a portion of a fiber / product by the system, where the material is dissolvable in at least one of the solvent(s) to form a solution and / or the material is solid or reactive to be solid in less than 50 °C (e.g., a room temperature, 25 °C ); where the first solvent having a high volatility with a boiling point of less than 80 °C (or less than 90 °C, or less than 75 °C, or less than 70 °C, or less than 65 °C, or less than 60 °C, or less than 55 °C, or less than 50 °C, or less than 45 °C) and; the second solvent having a lower volatility than the first solvent; where the second solvent having a boiling point of at least 10 °C higher (or at least 20 °C higher, or at least 30 °C higher, or at least 40 °C higher, or at least 50 °C higher, or at least 60 °C higher, or at least 70 °C higher, or at least 80 °C higher, or at least 90 °C higher, or at least 100 °C higher, or at least 110 °C higher) than the first solvent, or the second solvent having a boiling point of at least 80 °C, at least 90 °C, at least 100 °C, at least 110 °C, at least 120 °C, at least 130 °C, at least 140 °C, or at least 150 °C.Statement 2. A system according to Statement 1, where the collector or collector system is positioned in a distance from the nozzle(s) / spinneret(s) of less than about 50 mm, preferably in a range from about 500 microns to 30 mm, or more preferably in a range from 1 mm to 20 mm. Statement 3. A system according to Statement 1, where the electric potential is selected from a range of 100V-8kV, preferably a range of 100V-5000V, or more preferably a range of 1000V- 5000V, or at least 100 V, at least 200 V, at least 500 V, at least IkV, or less than lOkV, less than 8 kV, less than 5 kV, less than 4kV, less than 3kV, or any subranges therein.Statement 4. A system according to Statement 1, further comprising a motorized stage configured to move the nozzle(s) / spinneret(s) during the electrowriting, or where the nozzle(s) or spinneret(s) comprising moving nozzle(s) or spinneret(s)Statement 5. A system according to Statement 1, where the collector comprises a moving collector (e.g., a rotating mandrel, or a (second) motorized stage configured to move the collector).A system can choose either moving nozzle(s) or moving collector, or the combination thereof. Statement 6. A system according to Statement 1, where at least a portion of the fluid stock further comprises one or more additive(s) selected from a conductive agent, a therapeutic agent, a dye, an indicator agent, a drug, or any combination thereof.Statement 7. A system according to Statement 1, where the temperature of the fluid stock (solution) is less than 80 °C, less than 70 °C, less than 60 °C, less than 50 °C, less than 40 °C, less than 30 °C before, during and / or after the fluid stock coming (or spinning) out of the nozzle(s).Statement 8. A system according to Statement 1, where the material in the fluid stock comprising a polymer having a melting temperature of at least 60 °C, at least 100 °C, at least 150 °C, at least166 °C, at least 170 °C, at least 180 °C, at least 190 °C, at least 200 °C, at least 210 °C, at least220 °C, at least 230 °C, at least 240 °C, at least 250 °C, at least 260 °C, at least 270 °C, at least280 °C, at least 290 °C, or at least 300 °C.Statement 9. A system according to Statement 1, where the fluid stock is a solution comprising two polymers and / or at least two solvents.Statement 10. A system according to Statement 1, where the fluid stock comprising a first polymer having a degradation rate of at least 50% of the polymer degraded in less than one year, less than 9 month, less than 6 month, less than 3 month in a physiological environment or a biological environment; and a second polymer having a degradation rate of at most 50% of thepolymer degraded in more than one year, more than 1 .5 year, more than 2 year, more than 2.5 year, or more than 3 year in a physiological environment or a biological environment.Statement 11. A system according to Statement 5, where the rotating mandrel rotates with a rotation speed (VR) selected from a range of 0.5-20 cm / s or preferably 1-10 cm / s.Statement 12. A system according to Statement 1, where the first solvent is 10%-100% of the total solvent, or 20%-80% of the total solvent, or preferably 25%-75% of the total solvent. Statement 13. A system according to Statement 1, where the second solvent is l%-90% of the total solvent, or 10%-80% of the total solvent, or preferably 25%-75% of the total solvent. Statement 14. A system according to Statement 1, where the ratio of first solvent to the second solvent is selected from a range of 1 :99 - 99: 1, or 1 :9 to 9: 1, or 1 :4 to 4:1, or 1 :3 to 3: 1, at least 1 :99, 1 : 9, 1 :8, 1 :7, 1 : 6, 1:5, 1 :4, 1 : 3, 1 :2, or 1 : 1, or at most 99: 1, at most 9: 1, 8: 1, 7:1, 6: 1, 5: 1, 4: 1, 3: 1, 2: 1, or 1 : 1, or any combination thereof.Statement 15. A system according to Statement 1, where the first solvent is selected from HFIP, Dichloromethane, acetone, Chloroform, Methanol, Tetrahydrofuran or any combination thereof. Statement 16. A system according to Statement 1, where the second solvent is selected from Anisole, N,N-Dimethylformamide, Dioxane, Dimethyl Sulfoxide (DMSO) or any combination thereof.Statement 17. A system according to Statement 1, where the fluid stock has a polymer concentration selected from a range of 5% to 50% W / V, preferably 15% to 40% W / V, or more preferably 20% to 30% W / V.Statement 18. A system according to Statement 1, comprising a plurality of nozzles, or at least three nozzles, or an array of nozzles or two array of nozzles.Statement 19. A system according to Statement 1, comprising a first nozzle or first array of nozzles configured to form a group of filaments uniformly aligned in a first direction, and a second nozzle or second array of nozzles configured to form a group of filaments uniformly aligned in a second direction; and optionally the first direction and the second direction forms an angle with a degree selected from a range of 15° to 90°, or a range of 25° to 80° or more preferably from 35° to 75°.Statement 20. A method of controlling a fiber stacking for solution electrowriting, comprising providing a system according to Statement 1, increasing the ratio of the first solvent to the second solvent to increase the fiber stacking height for the same layers of stacking fibers withsubstantially the same diameter of fibers; and / or decreasing the ratio of the first solvent to the second solvent to decrease the fiber staking height for the same layers of stacking fibers with substantially the same diameter of fibers.Statement 21. A method of controlling a fiber fusion for solution electrowriting, comprising providing a system according to Statement 1, increasing the ratio of the first solvent to the second solvent to decrease the fiber fusion in the intersection(s) of fibers (e.g., fiber crossing points), and / or decreasing the ratio of the first solvent to the second solvent to increase the fiber fusion in the intersection of fibers.Statement 22. A product made by the system according to Statement 1, comprising at least three layers of (uniaxially, or biaxially, or multi-axially, oriented) fibers, where for each axis / orientation / direction, the adjacent fibers in different layers are vertically stacked and aligned one over another; and the adjacent fibers in the same layer are horizontally separated in a substantially constant distance (or space apart).Statement 23. A product made by the system according to Statement 1, comprising at least three layers of (uniaxially, or biaxially, or multi-axially, oriented) fibers, where for each axis / orientation / direction, the adjacent fibers in different layers are vertically staggered and aligning one over another; and the adjacent fibers in the same layer are horizontally separated in a distance.Statement 24. A product made by the system according to Statement 1, comprising two groups of aligned fibers (biaxially aligned fibers) aligned in two directions with a substantially constant winding angle, where the winding angle is selected from a range of 15° to 90°, a range of 25° to 80° or more preferably from 35° to 75°.Statement 25. A method of making a biocompatible scaffold, comprising providing a fluid stock comprising at least one biocompatible polymer and at least two solvents, where a first solvent having high volatility with a boiling temperature of less than 80 °C (or less than 90 °C, or less than 75 °C, or less than 70 °C, or less than 65 °C, or less than 60 °C, or less than 55 °C, or less than 50 °C, or less than 45 °C) and; a second solvent having a lower volatility than the first solvent; where the second solvent having a boiling temperature of at least 10 °C higher ( or at least 20 °C higher, or at least 30 °C higher, or at least 40 °C higher, or al least 50 °C higher, or at least 60 °C higher, or at least 70 °C higher, or at least 80 °C higher, or at least 90 °C higher, or at least 100 °C higher, or at least 110 °C higher)than the first solvent, or the second solvent having a boiling temperature of at least 80 °C, at least 90 °C, at least 100 °C, at least 110 °C, at least 120 °C, at least 130 °C, at least 140 °C, or at least 150 °C; injecting / electrospinning / electrowriting the fluid stock (at a temperature of less than 80 °C, or less than 70 °C, or less than 60 °C, or less than 50 °C, or less than 40 °C, or less than 37 °C) to make one or a plurality of fibers by using an electrospinning device or an electrowriting device (in an ambient environment) to form a predetermined structure of the biocompatible scaffold; heating the scaffold (in a temperature selected from 50 °C -160 °C, or 70 °C -150 °C, or 80 °C - 110 °C, or at least 60 °C, or at least 70 °C, or at least 80 °C, or at least 90 °C, or at least 100 °C, or at most 200 °C, or at most 170 °C, or at most 150 °C or at most 120 °C or any combination thereof) to remove residual solvent (e.g., second solvent).Statement 26. A method of making a biocompatible scaffold by using the system according to Statement 1.Statement 27. A product / scaffold comprising at least three layers of fibers, each fiber comprising at least one polymer or at least two polymers; and optionally an additive distributed in at least one fiber or at least one polymer; where the adjacent fibers in adjacent layers are staggered or vertically aligned one over another, and the adjacent fibers in the same layer are spaced from each other, optionally where the additive could be uniformly distributed in at least one fiber and / or encapsulated by the polymer(s) in at least one fiber. (In some examples, the polymer(s) comprise biocompatible polymer(s) and / or biodegradable polymer(s) and / or biocompatible biodegradable polymer(s).)Statement 28. A product / scaffold according to Statement 27, where the additive is uniformly distributed in the fiber material or the polymer (in a constant concentration), or bind / attach to at least one polymer(s); and / or the additive could be dissolved in solution, or dispersed as particles in solution of claim 6.Statement 29 A product / scaffold according to Statement 27, where the additive is a therapeutic agent or a drug, configured to gradually deliver to a physiological environment after implanting the product into the physiological environment.Statement 30. A product / scaffold according to Statement 27, where the product comprising at least two (biocompatible) polymers, where a first polymer having a degradation rate of at least 50% of the polymer degraded in less than one year, less than 9 month, less than 6 month, lessthan 3 month in a physiological environment or a biological environment; and a second polymer having a degradation rate of at most 50% of the polymer degraded in more than one year, more than 1.5 year, more than 2 year, more than 2.5 year, or more than 3 year in a physiological environment or a biological environment.Statement 31. A product / scaffold according to Statement 27, where the product is an implantable medical device or a scaffold of an artificial tissue.Statement 32. A product / scaffold according to Statement 27, where the two (biocompatible) polymers are mixed to form the same / single fiber or are injected / emanated / electrospun / electrowritten from the same nozzle.Statement 33. A product / scaffold according to Statement 27, where the two (biocompatible) polymers forms separate / different fibers and / or arranged in a predetermined pattern (e.g., one fiber of a first polymer is next to another fiber of a second polymer), or injected / emanated / electrospun / electrowritten from different nozzles (e.g., a first nozzle for a first polymer and an adjacent second nozzle for a second polymer).Statement 34. A product / scaffold according to Statement 27, where the at least one polymer or at least two polymers is / are selected from Polyglycolide or Polyglycolic acid (PGA), Polylactic acid (PLA), Polycaprolactone (PCL), Polyhydroxyalkanoate (PHA), Polyhydroxybutyrate (PHB), Polyethylene adipate (PEA), Polybutylene succinate (PBS), Poly (3-hydroxybutyrate-co- 3 -hydroxy valerate) (PHBV), Polyethylene terephthalate (PET), Polybutylene terephthalate (PBT), polyethylene glycol (PEG), Polytrimethylene terephthalate (PTT), Polyethylene naphthalate (PEN), Poly(glycerol-sebacate) (PGS), Palmitate Functionalized poly(glycerol sebacate (PGSP), and / or poly(epsilon caprolactone) (PCL), or the derivatives of these polymers. Statement 35. A product / scaffold according to Statement 27, where the first polymer is selected from PGSP and / or the second polymer is selected from Polyethylene terephthalate (PET). Statement 36. A product / scaffold according to Statement 27, made by the method of claim 30 using the system according to claim 1.Statement 37. A product / scaffold according to Statement 27, where the fibers are biaxially oriented and aligned in two directions.Statement 38. A product / scaffold according to Statement 27, comprising at least three layers of biaxially oriented fibers, where for each axis / orientation / direction, the adjacent fibers in different layers are vertically staggered / stacked and aligned one over another; and the adjacentfibers in the same layer are horizontally separated in a distance to form a plurality of pores / holes / cavities in the scaffold.Statement 39. A product / scaffold according to Statement 27, where the average size of the pores / holes / cavities is larger than a size of a cell (e.g., at least 1 micron, at least 5 microns, at least 10 microns, at least 20 microns, at least 30 microns, at least 40 microns, at least 50 microns, etc.).Statement 40. A product / scaffold according to Statement 27, where the average diameter of the fibers is selected from 1 nm - 20 microns, at least 5 nm, at least 10 nm, at least 20 nm, at least 50 nm, at least 100 microns, at least 200 microns, at least 500 microns, at least 1 micron, at least 5 microns, at least 10 microns, at least 20 microns, at least 30 microns, or at least 50 microns. Statement 41. A product / scaffold according to Statement 27, where the scaffold is a conduit, a web, a shape of at least a portion of an organ.Statement 42. A product / scaffold according to Statement 27, where fibers in the scaffold have a plurality of fusion points between two intersected fibers at an average frequency selected from a range of 5% to 99%, or 5 % to 90%, or 10% to 60%, or at least 5%, or at least 7%, or at least 10% , or at least 15 %, or at least 20%, or at least 30%, or at most 99 %, or at most 90 %, or at most 80%, or at most 70 %, or at most 60 %, or at most 50%.Statement 43. A product / scaffold according to Statement 27, where the fibers in the scaffold have a stacking height or thickness of at least 10 microns, or at least 20 microns, or at least 30 microns, or at least 40 microns, or at least 50 microns, or at least 60 microns, or at least 70 microns, or at least 80 microns, or at least 90 microns, or at least 100 microns, or at least 150 microns, or at least 200 microns, or at least 250 microns.Statement 44. A product / scaffold according to Statement 27, where the ratio of the two polymers are selected from a range of 1:9 to 9:1, 1: 5 to 5: 1, 1 :4 to 4: 1, 1 :3 to 3: 1, 1 :2 to 2: 1, at least 1 :99, 1 : 9, 1 :8, 1 :7, 1 : 6, 1:5, 1 :4, 1 : 3, 1 :2, or 1 : 1, or at most 99: 1, at most 9: 1, 8: 1, 7: 1, 6: 1, 5: 1, 4: 1, 3 : 1, 2: 1, or 1 : 1, or any combination thereof.Statement 45. A product / scaffold according to Statement 27, further comprising a water-soluble sacrificial layer on the bottom surface of the product / scaffold configured to be dissolvable in water to facilitate scaffold removal from the collector.Statement 46. A product / scaffold according to Statement 27, where the sacrificial layer comprises a sodium hyaluronate (HA).Statement 47. A method according to Statement 26, where a rotation speed of the rotating mandrel (VR) is selected from a range of 0.5-20 cm / s or preferably 1-10 cm / s, a speed of the motorized stage speeds is selected from a range of 0.5-20 cm / s or preferably 1-15 cm / s. Statement 48. A system according to Statement 1, where the collector system comprises a mandrel, such as for example, a mandrel comprising a diameter of 0.5 mm to 30 mm, including all 0.005 mm values and ranges therebetween.Statement 49. A product / scaffold according to Statement 27, where fibers in the scaffold have a plurality of fusion points between two intersected fibers such that for each fusion point (or late least one fusion point) a bottom surface of a first fiber sticks to a top surface of a second fiber with an overlapped distance of less than 10% (or less than 15%, less than 5%, less than 4%, less than 3%, less than 2%, or less than 1%) of the diameter of the first fiber and / or second fiber. Statement 50. A product / scaffold according to Statement 27, where the pores / holes / cavities having a shape selected from cube or cuboid.Statement 51. A system according to Statement 6, where the conductive agent is selected from a salt, or a (biocompatible) conductive polymer, or a material configured to increase the electrical conductivity of the solution.Statement 52. A method of making a solution electrowritten fibrous product, the method comprising: providing a solution electrowriting system comprising: one or more nozzle(s); a material supply system comprising one or more reservoir(s) fluidically coupled to the nozzle(s) and configured to supply one or more fluid stock(s) to the nozzle(s) thereby ejecting one or more jet stream(s) of the fluid stock(s) from the nozzle(s); a collector system configured to collect one or more fiber(s) formed by the jet stream(s) ejected from the nozzle(s); and, optionally, one or more power source(s) configured to provide one or more electric potential(s) to each of the nozzle(s) and, optionally, to the collector system, thereby providing one or more electric potential difference(s) between the collector system and each of the nozzle(s); where each fluid stock comprises a solution comprising at least one first solvent and, optionally, at least one second solvent, and one or more material(s) configured to form at least a portion of a fiber upon ejection of the jet stream(s) of the fluid stock(s) from the nozzle(s), where the material(s) is / are dissolvable in at least one of the solvent(s) to form a solution; ejecting the fluid stream(s) of the fluid stock(s) from the nozzle(s) to form the fiber(s); collecting the fiber(s) with the collector system to form a fibrous product comprising one or more fiber(s) arranged in a predeterminedpattern disposed on (e g., forming an outer layer, sheath, or the like) at least a portion of the exterior surfaces of a layer comprising one or more porous elastomer(s) (at least a portion of or all of which may be porous biodegradable elastomer(s) or the like) (e.g., a porous elastomer layer or layers independently comprising one or more chelation crosslinked polymer(s)) (such as, for example, PAS or the like, or any combination thereof) (e.g., an inner layer, a core, or the like); and releasing the fibrous product (e.g., a product comprising a hybrid structure or the like) from collector system, where a desired fiber fusion and / or a desired fiber stacking is observed in the fibrous product, or ejecting one or more fluid stream(s) of one or more fluid stock(s) from one or more nozzle(s) of a solution electrowriting system comprising: the one or more nozzle(s); a material supply system comprising one or more reservoir(s) fluidically coupled to the nozzle(s) and configured to supply one or more fluid stock(s) to the nozzle(s) thereby ejecting one or more jet stream(s) of the fluid stock(s) from the nozzle(s); a collector system configured to collect one or more fiber(s) formed by the jet stream(s) ejected from the nozzle(s); and, optionally, one or more power source(s) configured to provide one or more electric potential(s) to each of the nozzle(s) and, optionally, to the collector system, thereby providing one or more electric potential difference(s) between the collector system and each of the nozzle(s); where each fluid stock comprises a solution comprising at least one first solvent and, optionally, at least one second solvent, and one or more material(s) configured to form at least a portion of a fiber upon ejection of the jet stream(s) of the fluid stock(s) from the nozzle(s), where the material(s) is / are dissolvable in at least one of the solvent(s) to form a solution, to form a plurality of fiber(s); collecting the plurality of fiber with a collector system to form a fibrous product comprising the plurality of fiber arranged in a predetermined pattern disposed on at least a portion of the exterior surfaces of a layer comprising one or more porous elastomer(s); and releasing the fibrous product from the collector system, where a desired fiber fusion and / or a desired fiber stacking is observed in the fibrous product. Statement 53. A method according to Statement 52, further comprising, after the collecting and / or the releasing, heating and / or drying the fibrous product.Statement 54. A method according to Statement 52, where the fluid stock(s) comprise(s) at least one first solvent and at least one second solvent, and where the at least one first solvent has aboiling point of less than about 80 °C, and where the at least one second solvent has a boiling point of at least about 80 °C or greater.Statement 55. A method according to Statement 52, where the fluid stock(s) comprise(s) at least one first solvent and at least one second solvent, and where the boiling point of the at least one second solvent is from about 10 °C to about 200 °C higher than the boiling point of the at least one first solvent.Statement 56. A method according to Statement 54, where the at least one first solvent is chosen from diethyl ether, dichloromethane (DCM), acetone, 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), chloroform, methanol, tetrahydrofuran (THF), trifluoroethanol (TFE), ethanol, acetonitrile, cyclohexane, benzene, ethyl acetate, hexane, trifluoroacetic acid, isopropanol, and any combination thereof; and / or where the at least one second solvent is chosen from water, dioxane, toluene, pyridine, N,N-dimethylformamide (DMF), anisole, dimethyl sulfoxide (DMSO), 1,2- di chloroethane, triethylamine, heptane, butanol, acetic acid, xylene, diglyme (diethylene glycol diethyl ether), and any combination thereof.Statement 57. A method according to Statement 54, where the volume ratio of the at least one first solvent to the at least one second solvent is from about 1.99 to about 99: 1.Statement 58. A method according to Statement 52 or 54, where the fibrous product comprises a plurality of fusion points between respective portions of at least two adjacent intersected fibers, such that for each fusion point, a bottom surface of a first fiber is bonded to a top surface of a second fiber.Statement 59. A method according to Statement 58, where the plurality of fusion points between adjacent intersected fibers is observed at an average frequency of about 5% to about 99%.Statement 60. A method according to Statement 52, where the fluid stock(s) comprise(s) at least one first solvent having a boiling point of about 70 °C to about 120 °C.Statement 61. A method according to Statement 60, where the at least one first solvent is chosen from trifluoroethanol (TFE), ethanol, acetonitrile, cyclohexane, benzene, ethyl acetate, hexane, trifluoroacetic acid, isopropanol, water, dioxane, toluene, pyridine, and any combination thereof. Statement 62. A method according to Statement 60, where the fibers comprise a plurality of fusion points between respective portions of at least two adjacent intersected fibers, such that for each fusion point, a bottom surface of a first fiber is bonded to a top surface of a second fiber.Statement 63. A method according to Statement 62, where the plurality of fusion points between adjacent intersected fibers is observed at an average frequency of about 5% to about 99%.Statement 64. A method according to Statement 52, where the fluid stock(s) comprise(s) at least one first solvent and at least one second solvent, and where the at least one first solvent has a dipole moment of about 1.5 D to about 4.2 D and the at least one second solvent has a dipole moment of about 0 D to less than about 1.5 D.Statement 65. A method according to Statement 52, where the fluid stock(s) comprise(s) at least one first solvent and at least one second solvent, and where the dipole moment of the at least one first solvent is about 20 % or more greater than the dipole moment of the at least one second solvent.Statement 66. A method according to Statement 65, where the at least one first solvent is chosen from dichloromethane, tetrahydrofuran (THF), pyridine, trifluoroethanol, acetone, ethanol, methanol, N,N-Dimethylformamide, dimethyl sulfoxide (DMSO), isopropanol, water, ethyl acetate, trifluoroacetic acid, 1, 1,1,3,3,3-hexafluoroisopropanol, 1-butanol, 1,2-di chloroethane, acetic acid, diglyme, acetonitrile, and any combination thereof; and / or the at least one second solvent is chosen from cyclohexane, hexane, benzene, toluene, dioxane, diethyl ether, chloroform, anisole, triethylamine, heptane, xylene, and any combination thereof.Statement 67. A method according to Statement 66, where the volume ratio of the at least one first solvent to the at least one second solvent is from about 1 :99 to about 99: 1.Statement 68. A method according to Statement 66, where for each axial direction of the fibrous product, adjacent fibers of different layers are aligned and are vertically stacked.Statement 69. A method according to Statement 52, where the fluid stock(s) comprise(s) at least one first solvent having a dipole moment of about 1.5 D to about 4.2 D.Statement 70. A method according to Statement 52, where the at least one first solvent is chosen from dichloromethane, tetrahydrofuran (THF), pyridine, trifluoroethanol, acetone, ethanol, methanol, N,N-Dimethylformamide, dimethyl sulfoxide (DMSO), isopropanol, water, ethyl acetate, trifluoroacetic acid, 1,1,1,3,3,3-hexafluoroisopropanol, 1-butanol, 1,2-dichloroethane, acetic acid, diglyme, acetonitrile, and any combination thereof.Statement 71. A method according to Statement 69, where for each axial direction of the fibrous product, adjacent fibers of different layers are aligned and are vertically stacked.Statement 72. A method according to Statement 52, where the fluid stock(s) further comprise(s) a conductive agent.Statement 73. A method according to Statement 72, where the conductive agent is chosen from a salt, a conductive polymer, and any combination thereof.Statement 74. A method according to Statement 73, where the salt is present in the fluid stock(s) at from about 0.01 weight % to about 10 weight %, based on the total weight of the material(s), or where the conductive polymer is present in the fluid stock(s) at from about 0.1 weight % to about 100 weight %, based on the total weight of the material(s).Statement 75. A method according to Statement 72, where for each axial direction of the fibrous product, adjacent fibers of different layers are aligned and are vertically stacked.Statement 76. A method according to Statement 52, where the electric potential applied to the nozzle(s) is from about 50V to about 8kV.Statement 77. A method according to Statement 76, where for each axial direction of the fibrous product, adjacent fibers of different layers are aligned and are vertically stacked.Statement 78. A method according to Statement 52, where the fibrous product comprises one or more layer(s) each comprising one or more group(s) of fibers optionally aligned in one or more axial directions of the fibrous product within and / or between the layer(s).Statement 79. A method according to Statement 78, where the group(s) of fibers is / are uniaxially, biaxially, or multi-axially oriented within and / or between the layer(s).Statement 80. A method according to Statement 78, where each group of fibers has a substantially constant winding angle, relative to the longitudinal axis of the fibrous product. Statement 81. A method according to Statement 80, where the substantially constant winding angle is or comprises an angle from or between about 1° to about 89°, relative to the longitudinal axis of the fibrous product.Statement 82. A method according to Statement 52, where the electric potential is from about 50V to about 8kV.Statement 83. A method according to Statement 52, where the volume ratio of the at least one first solvent to the at least one second solvent is from about 1 :99 to about 99: 1.Statement 84. A method according to Statement 52, where the one or more material(s) comprise(s) or each fiber of the plurality of one or more material(s) independently comprises comprise at least one polymer.Statement 85. A method according to Statement 84, where the at least one polymer comprises at least one biocompatible polymer (such as, for example, at least one chelation crosslinked polymer or the like) and / or at least one biodegradable polymer (such as, for example, at least one chelation crosslinked polymer or the like).Statement 86. A method according to Statement 84, where the at least one polymer is thermo- reactive at a temperature of at least about 60 °C.Statement 87. A method according to Statement 84, where the at least one polymer is chosen from a polyester, polyurethane, polyether, polyketal, polyimide, polyamide, polycarbonate, polyacrylate, polysaccharide, and any combination thereof.Statement 88. A method according to Statement 84, where the at least one polymer is chosen from polyglycolide or a polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone (PCL), polyhydroxyalkanoate (PHA), polyhydroxybutyrate (PHB), polyethylene adipate (PEA), polybutylene succinate (PBS), poly(3-hydroxybutyrate-co-3 -hydroxy valerate) (PHBV), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyethylene glycol (PEG), polytrimethylene terephthalate(PTT), polyethylene naphthalate (PEN), poly(glycerol-sebacate) (PGS), palmitate functionalized poly(glycerol sebacate (PGSP), poly(epsilon caprolactone) (PCL), polymethyl methacrylate (PMMA), chitosan, gelatin, cellulose, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), polydioxanone, derivatives thereof, and any combination thereof. Statement 89. A method according to Statement 84, where the at least one polymer has a concentration in the fluid stock(s) of about 5% to about 90% w / V.Statement 90. A method according to Statement 84, where the fluid stock(s) comprising the at least one polymer is / are ejected from the nozzle(s) to form one or more fiber(s) comprising the at least one polymer.Statement 91. A method according to Statement 84, where at least one fluid stock comprises at least one first polymer and at least one second polymer, and / or where at least a first fluid stock comprises at least one first polymer and at least one second fluid stock comprises at least a second polymer.Statement 92. A method according to Statement 84, where the fluid stock(s) comprising the at least one first polymer and the at least one second polymer are ejected from the same or different nozzle(s) to form one or more fiber(s) comprising the at least one first polymer and / or the at least one second polymer.Statement 93. A method according to Statement 52, where the fluid stock(s) further comprise(s) at least one additive.Statement 94. A method according to Statement 93, where the at least one additive is chosen from a therapeutic agent, a dye, an indicator agent, a drug, and any combination thereof. Statement 95. A method according to Statement 93, where the at least one additive is dissolved in or dispersed as particles in the fluid stock(s).Statement 96. A method according to Statement 52, where the fibrous product has an inner diameter of about 0.5 mm to about 300 mm and / or an outer diameter of about 0.51 mm to about 300 mm.Statement 97. A method according to Statement 52, where the average diameter of the fibers is from about 100 nm to about 500 microns.Statement 98. A method according to Statement 52, further comprising one or more times during formation of the fiber(s) one or more or all of the following: altering the volume ratio of the at least one first solvent to the at least one second solvent in the fluid stock(s); adding at least a third solvent to the fluid stock(s); altering the concentration of a conducting agent in the fluid stock(s); and altering the electric potential(s) applied to the nozzle(s), if applied, altering spinneret translation, altering speed of collector rotation, or altering the winding angle and / or predetermined fiber pattern, where fiber fusion, fiber stacking, or a combination thereof is altered.Statement 99. A product comprising a multilayer or hybrid structure comprising a layer comprising one or more porous elastomer(s) (e.g., at least a portion or all of which are porous biodegradable elastomer(s) or the like) (e.g., porous elastomer(s) independently comprise(s) one or more chelation crosslinked polymer(s) (e.g., metalloelastomer(s), such as, for example, porous metalloelastomer(s), any one or all of which may be biodegradable, or the like) (e.g., an inner layer, a core or the like); and one or more layer(s) of fibers (e.g., electrowritten fibers, electrospun fibers, or the like, or any combination thereof) (e.g., an outer layer, a sheath or the like), where the fibers are arranged in a predetermined pattern; the average diameter of the fibers is from about 100 nm to about 500 microns; or the product comprises a desired fiber fusion and / or fiber stacking; or any combination thereof, and at least one of the layer(s) or one or more layer(s) are disposed on the layer comprising one or more porous elastomer(s) (e.g., at least aportion or all of which may be porous biodegradable elastomer(s) or the like) (e.g., porous elastomer(s) independently comprise(s) one or more chelation crosslinked polymer(s)), or an inner layer comprising one or more porous elastomer(s); and one or more layer(s) of electrowritten fibers, where the fibers are arranged in a predetermined pattern; the average diameter of the fibers is from about 100 nm to about 500 microns; or the product comprises a desired fiber fusion and / or fiber stacking; or any combination thereof, and at least one of the layer(s) or one or more layer(s) are disposed on the inner layer comprising one or more porous elastomer(s).Statement 100. A product according to Statement 99, where at least a portion of the fiber(s) or each fiber comprises one or more material(s) which is / are thermo-reactive at a temperature of at least 60 °C.Statement 101. A product according to Statement 99, where the product comprises a plurality of fusion points between respective portions of at least two intersected fibers, such that for each fusion point, a bottom surface of a first fiber is bonded to a top surface of a second fiber. Statement 102. A product according to Statement 101, where the plurality of fusion points between adjacent intersected fibers is observed at an average frequency of about 5% to about 99%.Statement 103. A product according to Statement 99, where for each axial direction of the product, the adjacent fibers in different layers are aligned one over the other and are vertically stacked or vertically staggered.Statement 104. A product according to Statement 99, where each layer comprises one or more group(s) of fibers optionally aligned in one or more axial directions of the product within and / or between the layer(s).Statement 105. A product according to Statement 104, where the group(s) of fibers is / are uniaxially, biaxially, or multi-axially oriented within and / or between the layer(s).Statement 106. A product according to Statement 104, where each group of fibers has a substantially constant winding angle.Statement 107. A product according to Statement 106, where the winding angle comprises or is an angle from or between about 1° to about 89°.Statement 108. A product according to Statement 99, where the predetermined pattern of fibers defines in the product a plurality of pores extending at least partially through the product. Statement 109. A product according to Statement 108, where the average width of the pores is at least 1 micron.Statement 110. A product according to Statement 108, where the pores are characterized by a cross-sectional shape in the form of a cube, a cuboid, a rhombohedron, or a rhomboid.Statement 111. A product according to Statement 99, where the one or more material(s) comprise(s) or the electrowritten fibers independently comprise at least one polymer at least one polymer.Statement 112. A product according to Statement 111, where the at least one polymer comprises at least one biocompatible polymer (such as, for example, at least one chelation crosslinked polymer or the like) and / or at least one biodegradable polymer (such as, for example, at least one chelation crosslinked polymer or the like).Statement 113. A product according to Statement 111, where the at least one polymer is thermo- reactive at a temperature of at least about 60 °C.Statement 114. A product according to Statement 111, where the at least one polymer is chosen from a polyester, polyurethane, polyether, polyketal, polyamide, polyimide, polycarbonate, polyacrylate, polysaccharide, and any combination thereof.Statement 115. A product according to Statement 114, where the at least one polymer is chosen from polyglycolide or a polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone (PCL), polyhydroxyalkanoate (PHA), polyhydroxybutyrate (PHB), polyethylene adipate (PEA), polybutylene succinate (PBS), poly(3-hydroxybutyrate-co-3 -hydroxy valerate) (PHBV), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyethylene glycol (PEG), polytrimethylene terephthalate(PTT), polyethylene naphthalate (PEN), poly(glycerol-sebacate) (PGS), palmitate functionalized poly(glycerol sebacate (PGSP), poly(epsilon caprolactone) (PCL), polymethyl methacrylate (PMMA), chitosan, gelatin, cellulose, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), polydioxanone, derivatives thereof, and any combination thereof. Statement 116. A product according to Statement 108, where at least one fiber comprises at least one first polymer and at least one second polymer, and / or where at least one first fiber comprises at least one first polymer and at least second fiber comprises at least one second polymer.Statement 117. A product according to Statement 99, where at least one fiber further comprises at least one additive.Statement 118. A product according to Statement 117, where the at least one additive is chosen from a therapeutic agent, a dye, an indicator agent, a drug, and any combination thereof.Statement 119. A product according to Statement 99, where the product has an inner diameter of about 0.5 mm to about 300 mm and / or an outer diameter of about 0.51 mm to about 600 mm.Statement 120. A product according to Statement 99, where the product is a conduit, a web, a patch, a mat, or a cuff.Statement 121. A product according to Statement 99, where the product comprises a shape of at least a portion of an organ, a vessel, or a body part.Statement 122. A product according to Statement 99, where the product is an implantable medical device or a scaffold of an artificial tissue.Statement 123. A product according to Statement 99, where the product is an arteriovenous graft. Statement 124. A product according to Statement 123, where the arteriovenous graft comprises a first orifice and a second orifice.Statement 125. A product according to Statement 124, where the first orifice comprises an inner linear dimension that is from about 10% to about 1000% larger than an inner linear dimension of the second orifice.Statement 126. A product according to Statement 123, where the arteriovenous graft comprises a first end and a second end.Statement 127. A product according to Statement 126, where the first end comprises an inner diameter and the second end comprises an inner diameter, and the ratio of first end inner diameter to second end inner diameter is from about 1.5: 1 to about 10: 1 and / or the ratio of first end wall thickness to second end wall thickness is from about 1 : 1.25 to about 1 : 100.

[0189] The steps of the methods described in the various examples disclosed herein are sufficient to carry out a method of the present disclosure. Thus, in various examples, a method consists essentially of a combination of the steps of the methods disclosed herein. In various other examples, a method consists of such steps.

[0190] The following examples are presented to illustrate the present disclosure. They are not intended to be limiting in any manner.EXAMPLE 1(0191 ] This example provides examples of products of the present disclosure, and methods of making and using same.101921 Electrowriting multilayered vascular grafts. Bilayer Graft Fabrication. The core of the graft was fabricated via porogen leaching of poly(methyl methacrylate) (PMMA) beads.

[0013] First, a custom cylindrical mold with a central stainless-steel mandrel was filled with spherical PMMA beads (38-45 pm (pm = micron(s)) diameter). The beads were tightly packed by sonicating the filled mold for 30 minutes. The mold was then heated at 175°C (°C = degree(s) Celsius) for 24 hr (hr = hour(s)) so that the surfaces of the beads partially fuse together. The fused PMMA bead template was then removed from the mold and loaded with a 30% m / V solution of PAS polymer, then dried in a vacuum to remove organic solvents. The PAS loaded PMMA template was then heated at 150°C for 12 hours to thermally crosslink the PAS polymer. After this step, the crosslinked PAS was no longer soluble, so the entire PAS / PMMA tube was submerged in a wash basin filled with acetone and dichloromethane to solubilize the PMMA beads. This PMMA leaching step leaves behind uniform, interconnected, spherical pores, as seen in FIG. 1. This concludes the core fabrication procedures, and at this point the core was placed on a stainless-steel mandrel so that the fibrous PCL sheath can be fabricated on the outside of the PAS core.

[0194] Electrowriting was used to form the PCL sheath. The PCL sheath can be modified to be “stronger” or more resistant to deformation by altering the angle of PCL fiber in the sheath, or by increasing the amount of fibers in the sheath. In the initial batch of sheep implants graft dilation was observed over time, so for the most recent batch of implants the amount of PCL fibers in the sheath was increased by 50%. Dilation was still observed in the grafts as they remodel, however, the dilation was decreased and stabilized rather than worsening as it did with the initial implants.|0195] The grafts were fabricated using a multilayered approach. The inner layer (core) of the graft was made by porogen leaching the chelation crosslinked elastomer PAS, and the outer fibrous layer of the graft (sheath) was made of electrowritten PCL fibers (FIG. 1). Grafts were implanted in sheep for as long as 100 days. The data in FIGS. 1-5 come from grafts implanted in sheep.

[0196] Ultrasound was used throughout the study to check in on the implanted grafts and ensure that there is blood flowing through the grafts (known as patency). Graft patency was demonstrated 100 days post-implant (FIG. 2).

[0197] Three sheep were euthanized 100 days after implant to perform histological analysis on explanted grafts. The images in FIGS. 3-5, and 9 were all obtained from a 100-day graft explant. The images in FIG. 7 were all obtained at or prior to implant. The images in FIG. 8 were all obtained from a 17-day and 100-day graft explant.EXAMPLE 2|0198| This example provides examples of products of the present disclosure, and methods of making and using same.

[0199] A tubular graft was fabricated using solution electrowriting with two distinct layers - as described in EXAMPLE 1. In this graft, Layer #1 (90% of the total graft) comprises a biodegradable elastomer PPIAS (a chelation crosslinking elastomer) electro written to create a pattern of fibers with a winding angle of 45°. FIG. 10A shows inner “lumen” of graft with 45° fibers. The remaining 10% of the graft, Layer #2, consists of PPIAS electrowritten to create a pattern of fibers with a winding angle of 55°. FIG. 10B shows outer “ablumen” of graft with 55° fibers.

[0200] This multi-layer graft was fabricated because a single layer graft consisting of 100% Layer #1 had a suture retention value that was suboptimal for implantation. By changing only 10% of the graft to comprise a second layer with a different pattern - albeit with an identical polymer composition - the suture retention of the graft (FIG. 10C) increased by 23.7% from 131.6±15.4 to 162.8±17.4 gram-force, a value that exceeds the suture retention force of human internal mammary artery (-140 gram-force). This suture retention test was done using a single suture loop and pulling until either the suture snapped, or the graft tore.

[9201] Further, this layering did not affect graft elastic modulus, demonstrating a novel approach to selectively tune graft mechanical properties. As seen in FIG. 1 ID, The elastic modulus of a graft consisting of 100% Layer #1 (1.24 MPa) was very similar to a graft consisting of 90% Layer #1, and 10% Layer #2 (1.12 MPa). However, ultimate tensile strength, in this case a proxy for suture retention because the graft failed at the suture line, increased by 29% from 1.99 MPa to 2.58 MPa. The data in FIG. 1 ID was obtained by suturing the entire graft betweentwo custom graft holders using running suture, then pulling the graft to 20% strain 100 times prior to pulling the graft to failure.|0202| By further modifying the balance of each layer 90%: 10% vs. 80%:20, 70%:30%, etc., or even adding additional layers with different fiber angles, different polymer compositions, the same polymer crosslinked with different metal ions, there is greater control over the properties of these grafts.

[0203] Although the present disclosure has been described with respect to one or more particular example(s), it will be understood that other examples of the present disclosure may be made without departing from the scope of the present disclosure.

Claims

CLAIMS:

1. A method of making a solution electrowritten fibrous product, the method comprising: ejecting one or more fluid stream(s) of one or more fluid stock(s) from one or more nozzle(s) of a solution electrowriting system comprising: the one or more nozzle(s); a material supply system comprising one or more reservoir(s) fluidically coupled to the nozzle(s) and configured to supply one or more fluid stock(s) to the nozzle(s) thereby ejecting one or more jet stream(s) of the fluid stock(s) from the nozzle(s); a collector system configured to collect one or more fiber(s) formed by the jet stream(s) ejected from the nozzle(s); and optionally, one or more power source(s) configured to provide one or more electric potential(s) to each of the nozzle(s) and, optionally, to the collector system, thereby providing one or more electric potential difference(s) between the collector system and each of the nozzle(s); wherein each fluid stock comprises a solution comprising at least one first solvent and, optionally, at least one second solvent, and one or more material(s) configured to form at least a portion of a fiber upon ejection of the jet stream(s) of the fluid stock(s) from the nozzle(s), wherein the material(s) is / are dissolvable in at least one of the solvent(s) to form a solution, to form a plurality of fiber(s); collecting the plurality of fiber with a collector system to form a fibrous product comprising the plurality of fiber arranged in a predetermined pattern disposed on at least a portion of the exterior surfaces of a layer comprising one or more porous elastomer(s); and releasing the fibrous product from the collector system, wherein a desired fiber fusion and / or a desired fiber stacking is observed in the fibrous product.

2. The method of claim 1, further comprising, after the collecting and / or the releasing, heating and / or drying the fibrous product.

3. The method of claim 1, wherein the fibrous product comprises a plurality of fusion points between respective portions of at least two adjacent intersected fibers, such that for each fusion point, a bottom surface of a first fiber is bonded to a top surface of a second fiber.

4. The method of claim 3, wherein the plurality of fusion points between adjacent intersected fibers is observed at an average frequency of about 5% to about 99%.

5. The method of claim 1, wherein the fluid stock(s) further comprise(s) a conductive agent.

6. The method of claim 5, wherein the conductive agent is chosen from a salt, a conductive polymer, and any combination thereof.

7. The method of claim 6, wherein the salt is present in the fluid stock(s) at from about 0.01 weight % to about 10 weight %, based on the total weight of the material(s), or wherein the conductive polymer is present in the fluid stock(s) at from about 0.1 weight % to about 100 weight %, based on the total weight of the material(s).

8. The method of claim 5, wherein for each axial direction of the fibrous product, adjacent fibers of different layers are aligned and are vertically stacked.

9. The method of claim 1, wherein the fibrous product comprises one or more layer(s) each comprising one or more group(s) of fibers optionally aligned in one or more axial directions of the fibrous product within and / or between the layer(s).

10. The method of claim 9, wherein the group(s) of fibers is / are uniaxially, biaxially, or multi - axially oriented within and / or between the layer(s).

11. The method of claim 27, wherein each group of fibers has a substantially constant winding angle, relative to the longitudinal axis of the fibrous product.

12. The method of claim 11, wherein the substantially constant winding angle is an angle from about 1° to about 89°, relative to the longitudinal axis of the fibrous product.

13. The method of claim 1, wherein each fiber of the plurality of one or more material(s) independently comprises at least one polymer.

14. The method of claim 13, wherein the at least one polymer comprises at least one biocompatible polymer and / or at least one biodegradable polymer.

15. The method of claim 13, wherein the at least one polymer comprises at least one chelation crosslinked polymer.

16. The method of claim 13, wherein the at least one polymer is chosen from a polyester, polyurethane, polyether, polyketal, polyimide, polyamide, polycarbonate, polyacrylate, polysaccharide, and any combination thereof.

17. The method of claim 16, wherein the at least one polymer is chosen from polyglycolide or a polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone (PCL), polyhydroxyalkanoate (PHA), polyhydroxybutyrate (PHB), polyethylene adipate (PEA), polybutylene succinate (PBS), poly(3-hydroxybutyrate-co-3 -hydroxy valerate) (PHBV), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyethylene glycol (PEG), polytrimethylene terephthalate(PTT), polyethylene naphthalate (PEN), poly(glycerol-sebacate) (PGS), palmitate functionalized poly(glycerol sebacate (PGSP), poly(epsilon caprolactone) (PCL), polymethyl methacrylate (PMMA), chitosan, gelatin, cellulose, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), polydioxanone, derivatives thereof, and any combination thereof.

18. The method of claim 13, wherein at least one fluid stock comprises at least one first polymer and at least one second polymer, and / or wherein at least a first fluid stock comprises at least one first polymer and at least one second fluid stock comprises at least a second polymer.

19. The method of claim 13, wherein the fluid stock(s) comprising the at least one first polymer and the at least one second polymer are ejected from the same or different nozzle(s) to form one or more fiber(s) comprising the at least one first polymer and / or the at least one second polymer.

20. The method of claim 1, wherein the fluid stock(s) further comprise(s) at least one additive.

21. The method of claim 20, wherein the at least one additive is chosen from a therapeutic agent, a dye, an indicator agent, a drug, a metal salt, and any combination thereof.

22. The method of claim 20, wherein the at least one additive is dissolved in or dispersed as particles in the fluid stock(s).

23. The method of claim 1, wherein the fibrous product has an inner diameter of about 0.5 mm to about 300 mm and / or an outer diameter of about 0.51 mm to about 300 mm and / or the average diameter of the fibers is from about 100 nm to about 500 microns.

24. The method of claim 1, further comprising one or more times during formation of the fiber(s) one or more or all of the following: altering the volume ratio of the at least one first solvent to the at least one second solvent in the fluid stock(s); adding at least a third solvent to the fluid stock(s); altering the concentration of a conducting agent in the fluid stock(s); and altering the electric potential(s) applied to the nozzle(s), if applied, altering spinneret translation, altering speed of collector rotation, or altering the winding angle and / or predetermined fiber pattern, wherein fiber fusion, fiber stacking, or a combination thereof is altered.

25. A product comprising a multilayer structure comprising an inner layer comprising one or more porous elastomer(s); and one or more layer(s) of electrowritten fibers, wherein:the fibers are arranged in a predetermined pattern; the average diameter of the fibers is from about 100 nm to about 500 microns; or the product comprises a desired fiber fusion and / or fiber stacking; or any combination thereof, and at least one of the layer(s) or one or more layer(s) are disposed on the inner layer comprising one or more porous elastomer(s).

26. The product of claim 25, wherein the product comprises a plurality of fusion points between respective portions of at least two intersected fibers, such that for each fusion point, a bottom surface of a first fiber is bonded to a top surface of a second fiber.

27. The product of claim 26, wherein the plurality of fusion points between adjacent intersected fibers is observed at an average frequency of about 5% to about 99%.

28. The product of claim 25, wherein for each axial direction of the product, the adjacent fibers in different layers are aligned one over the other and are vertically stacked or vertically staggered.

29. The product of claim 26, wherein each layer comprises one or more group(s) of fibers optionally aligned in one or more axial directions of the product within and / or between the layer(s).

30. The product of claim 53, wherein the group(s) of fibers is / are uniaxially, biaxially, or multi- axially oriented within and / or between the layer(s).

31. The product of claim 29, wherein each group of fibers has a substantially constant winding angle.

32. The product of claim 31, wherein the winding angle is from about 1° to about 89°.

33. The product of claim 25, wherein the predetermined pattern of fibers defines in the product a plurality of pores extending at least partially through the product.

34. The product of claim 33, wherein the average width of the pores is at least 1 micron.

35. The product of claim 33, wherein the pores are characterized by a cross-sectional shape in the form of a cube, a cuboid, a rhombohedron, or a rhomboid.

36. The product of claim 25, wherein the electrowritten fibers independently comprise at least one polymer.

37. The product of claim 36, wherein the at least one polymer comprises at least one biocompatible polymer and / or at least one biodegradable polymer.

38. The method of claim 36, wherein the at least one polymer comprises at least one chelation crosslinked polymer.

39. The product of claim 36, wherein the at least one polymer is chosen from a polyester, polyurethane, polyether, polyketal, polyamide, polyimide, polycarbonate, polyacrylate, polysaccharide, and any combination thereof.

40. The product of claim 39, wherein the at least one polymer is chosen from polyglycolide or a polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone (PCL), polyhydroxyalkanoate (PHA), polyhydroxybutyrate (PHB), polyethylene adipate (PEA), polybutylene succinate (PBS), poly(3-hydroxybutyrate-co-3 -hydroxy valerate) (PHBV), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyethylene glycol (PEG), polytrimethylene terephthalate(PTT), polyethylene naphthalate (PEN), poly(glycerol-sebacate) (PGS), palmitate functionalized poly(glycerol sebacate (PGSP), poly(epsilon caprolactone) (PCL), polymethyl methacrylate (PMMA), chitosan, gelatin, cellulose, polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), polydioxanone, derivatives thereof, and any combination thereof.41 . The product of claim 33, wherein at least one fiber comprises at least one first polymer and at least one second polymer, and / or wherein at least one first fiber comprises at least one first polymer and at least second fiber comprises at least one second polymer.

42. The product of claim 25, wherein at least one fiber further comprises at least one additive.

43. The product of claim 42, wherein the at least one additive is chosen from a therapeutic agent, a dye, an indicator agent, a drug, a metal salt, and any combination thereof.

44. The product of claim 42, wherein the product has an inner diameter of about 0.5 mm to about 300 mm and / or an outer diameter of about 0.51 mm to about 600 mm.

45. The product of claim 25, wherein the product is a conduit, a web, a patch, a mat, or a cuff.

46. The product of claim 25, wherein the product comprises a shape of at least a portion of an organ, a vessel, or a body part.

47. The product of claim 25, wherein the product is an implantable medical device or a scaffold of an artificial tissue.

48. The product of claim 25, wherein the product is an arteriovenous graft.

49. The product of claim 48, wherein the arteriovenous graft comprises a first orifice and a second orifice.

50. The product of claim 49, wherein the first orifice comprises an inner linear dimension that is from about 10% to about 1000% larger than an inner linear dimension of the second orifice.

51. The product of claim 48, wherein the arteriovenous graft comprises a first end and a second end.

52. The product of claim 51, wherein the first end comprises an inner diameter and the second end comprises an inner diameter, and the ratio of first end inner diameter to second end inner diameter is from about 1.5: 1 to about 10: 1 and / or the ratio of first end wall thickness to second end wall thickness is from about 1 : 1.25 to about 1 : 100.

53. The product of claim 48, wherein the arteriovenous graft exhibits a radial compliance of about 1 to about 80% / 100 mmHg.

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