Method for coating a cell with a biomimetic ZONA pellucida

Abstract

Provided herein are methods for coating a microparticle, cell, or therapeutic agent with a biomimetic zona pellucida (BZP). Also provided herein are BZP-coated cells prepared using the enclosed methods. The methods for using the BZP-coated microparticle to treat diabetes are also provided.

Description

Attorney Docket No.11196-120WO1 METHOD FOR COATING A CELL WITH A BIOMIMETIC ZONA PELLUCIDA CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to, and the benefit of, U.S. Provisional Patent Application No.63 / 642,521, filed May 3, 2024, which is incorporated by reference herein in its entirety. REFERENCE TO A SEQUENCE LISTING The sequence listing submitted on May 5, 2025, as an .XML file entitled “11196- 120WO1_ST26.xml” created on May 1, 2025, and having a file size of 27,608 bytes, is hereby incorporated by reference pursuant to 37 C.F.R. § 1.52(e)(5). FIELD The present disclosure relates to coating a microparticle, cell, or therapeutic drug with a biomimetic zona pellucida (BZP) and the use thereof. BACKGROUND Living cells have been widely studied as therapeutics. A typical example is the transplantation of islets for diabetes treatment. The Food and Drug Administration (FDA) approved the first-ever cell therapy for type 1 diabetes in 2023. As it is an allogeneic pancreatic islet cellular therapy, immunosuppressants have to be used throughout a patient’s lifetime, posing a considerable risk of infection and cancer development alongside other adverse side effects such as secondary diabetes, induced ^-cell apoptosis, fatigue, nephrotoxicity, hepatoxicity, and neurological complications. Islet cell encapsulation or coating for immunoisolation has been intensely studied to address this challenge. The concept of encapsulation is using a coating barrier to prevent transplanted cells from being recognized and attacked by the host’s immune system. Unfortunately, conventional encapsulation methods encounter persistent hurdles. Ideally, one transplantation will cure patients for their entire life, but this expectation may not be realized due to the gradual death, functional loss, and poor regeneration of ^ cells. Studies have shown that diabetic patients could live without insulin injections for only one to two years after the transplantation of microencapsulated islets. After intraportal transplantation (currently the main transplantation method), it is nearly impossible to remove microcapsules from the liver, surgically. However, microcapsules typically have a size ranging from ~500 to 1000 ^m, which is known to limit molecular transport and cell survival. After the death and loss of islets, thisAttorney Docket No.11196-120WO1 large volume of polymers prohibits the liver from repeatedly receiving new batches of microencapsulated islets. Also, many empty microcapsules are inevitably generated due to the Poisson distribution, requiring additional efforts to remove empty microcapsules and bringing new issues for manufacturing. Efforts have been made to develop conformal coating methods to minimize coating thickness and polymer volume. However, current state-of-the-art conformal coating methods face problems related to low pH, free radicals, shear stress, and / or coating deficiency. A recent study, unfortunately, showed that conformally coated islets did not improve diabetes treatment compared to naked ones, underscoring the need for further innovation in the quest for effective and safe islet delivery. What is needed is better islet cell encapsulation methods as a means to treat diabetes. SUMMARY The present disclosure relates to microparticles, cells, or therapeutic agents coated with a biomimetic zona pellucida (BZP), methods of coating the microparticles, cells, or therapeutic agents with BZP, and methods of using thereof. Accordingly, in one aspect, disclosed herein are microparticles (such as, for example, a biocompatible material including, but not limited to polystyrene, poly(lactic-co-glycolic acid) (PLGA), silica, and agarose), cells (such as, for example, mesenchymal stem cell, human neural stem cell, pancreatic islet, articular chondrocyte, fibroblast, red blood cell, platelet, cancer cell, and microbial cell (including, but not limited to bacteria, fungi, or yeast), or therapeutic agent (such as, for example, a drug or biologically active compound) coated with biomimetic zona pellucida (BZP) (i.e., a 3D polymer meshwork bound to a functionalized surface of the microparticle). In some aspects the BZP coated microparticle, cell, or therapeutic agent is 10-100 ^m in diameter. In some aspects, the BZP has a thickness between 10 to 30 µm. Also disclosed herein are microparticles, cells, or therapeutic agents of any preceding aspect wherein the surface of the microparticle, cell, or therapeutic agent is functionalized surface. In some aspects, the functionalized surface further comprises, an enzyme-binding molecule (such as, for example, an aptamer (such as, for example, anti-thrombin aptamer comprising a sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3), streptavidin, or biotinylated DNA aptamer) and an enzyme (such as, for example, a serine protease enzyme (such as, for example, thrombin), tyrosinase, transglutaminase, peroxidase, sortase, horseradish peroxidase, and alkaline phosphatase), which binds the enzyme-binding molecule. In one aspect, disclosed herein are microparticles, cells, or therapeutic agents of anyAttorney Docket No.11196-120WO1 preceding aspect wherein the 3D polymer meshwork of the BZP comprises a polymer coating, comprising a coating molecule (such as, for example, fibrinogen, fibrinogen conjugated to dibenzocyclooctyne (DBCO) (fibrinogen-DBCO)). In some aspects, the coating molecule is cleaved by the enzyme of any of the preceding aspects and assembled into the polymer coating (such as, for example, fibrin) on the surface of the microparticle, wherein the polymer coating is crosslinked with one or more blending molecules (such as, for example, alginate including, but not limited to alginate-azide. In some aspects, the polymer coating can be further crosslinked with one or more blending molecules of any of the preceding aspects by a fortifying solution (such as, for example, a solution comprising polylysine and calcium chloride), to form a hardened BZP. In some aspects, the coating molecule or one or more blending molecules is conjugated to dibenzocyclooctyne (DBCO), while the other, the coating molecule or one or more blending molecules, is conjugated to azide. Also disclosed herein is a method for coating a microparticle, cell (such as, for example, mesenchymal stem cell, human neural stem cell, pancreatic islet, articular chondrocyte, fibroblast, red blood cell, platelet, cancer cell, and microbial cell (such as, for example, bacteria, fungi, yeast)) or therapeutic agent with a biomimetic zona pellucida (BZP). In some aspects, the method is performed between about 0°C and about 37°C, and in some cases, it is performed at room temperature, comprises, (a) incubating the microparticle, cell, or therapeutic agent with an enzyme-binding molecule (such as, for example, an aptamer (such as for example, anti-thrombin aptamer comprising a sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3), streptavidin, or biotinylated DNA aptamer) conjugated to a cell membrane insertion moiety (such as, for example, cholesterol, a diacyl lipid, tocopherol, a ceramide, sphingomyelin, a phosphatidylcholine, a phosphatidylethanolamine, a phosphatidylserine, a glycolipid, and a fatty acid), (b) incubating the microparticle, cell, or therapeutic agent with an enzyme (such as, for example, a serine protease enzyme (such as, for example, thrombin), tyrosinase, transglutaminase, peroxidase, sortase, horseradish peroxidase, and alkaline phosphatase), and which binds the enzyme-binding molecule, (c) incubating the microparticle, cell, or therapeutic agent with a coating solution comprising a coating molecule (such as, for example, fibrinogen, fibrinogen conjugated to dibenzocyclooctyne (DBCO) (fibrinogen-DBCO)) that binds to the enzyme and is cleaved by the enzyme to form a polymer coating (such as, for example, fibrin) on the surface of the microparticle, cell, or therapeutic agent, (d) incubating the microparticle, cell, or therapeutic agent with a blending solution comprising one or more blending molecules (such as, for example, alginate and / or aginate-azide) that crosslinks with the polymer coating to form a hydrogel layer on the surface of the microparticle, cell, or therapeutic agent (e) incubating the microparticle, cell, or therapeutic agent with a fortifying solution, comprising polylysine andAttorney Docket No.11196-120WO1 calcium chloride, that hardens the BZP when reacted with at least one of the hydrogel and the polymer coating, (f) incubating the microparticle, cell, or therapeutic agent with the blending solution. In some aspects, the method can further comprise repeating steps (d) through (e). In some aspects, the method further comprises at least one of, washing the microparticle, cell, or therapeutic agent before step (a); washing the microparticle, cell, or therapeutic agent between steps (a) and (b); washing the microparticle, cell, or therapeutic agent between steps (b) and (c); washing the microparticle, cell, or therapeutic agent between steps (c) and (d); washing the microparticle, cell, or therapeutic agent between steps (e) and (f); and washing the microparticle, cell, or therapeutic agent after step (f). In some aspects, the coating molecule or the one or more blending molecule is conjugated to dibenzocyclooctyne (DBCO), and while the other, the coating molecule or the one or more blending molecule, is conjugated to azide. In one aspect, disclosed herein is a method for reducing or decreasing a blood glucose level and or treating, reducing, decreasing, inhibiting, ameliorating, and / or preventing diabetes in a subject in need thereof, the method comprising administering to the subject the microparticle, cell or therapeutic agent coated with a biomimetic zona pellucida (BZP) of any preceding aspect. For example, disclosed herein is a method for reducing or decreasing a blood glucose level and or treating, reducing, decreasing, inhibiting, ameliorating, and / or preventing diabetes in a subject, comprising administering to the subject a pancreatic islet cell coated with a biomimetic zona pellucida (BZP) said BZP comprising a 3D polymer meshwork bound to a functionalized surface of the pancreatic islet cell. In some aspects, the pancreatic islet cell coated with BZP exhibits a reduced degree of susceptibility to proinflammatory cytokines and decreases blood glucose level in a treated subject compared to a control (such as, for example, an untreated subject, a naked pancreatic islet cell, or a sample from the subject at an earlier time period, wherein the decreased blood glucose level indicates an effective treatment of diabetes. BRIEF DESCRIPTION OF THE DRAWINGS Figures 1A, 1B, 1C, 1D, 1E, and 1F examine aptamer-mediated molecular binding, assembly, and crosslinking. Figure 1A shows the schematic illustration of the process of BZP development. The process involves (i) aptamer-mediated thrombin immobilization on the cell membrane, (ii) thrombin-triggered fibrinogen assembly to form fibrin, and (iii) biomolecular crosslinking for BZP hardening. Figure 1B shows an analysis of aptamer-thrombin binding using flow cytometry. Three aptamers were analyzed. Apt: aptamer; c: control. Figure 1C shows confocal microscopy of aptamer-functionalized microparticles displaying FAM-labeled thrombin. Scale bar: 500 µm. Figure 1D shows characterization of aptamer-bound thrombin dissociation and retention. The half-life of thrombin retention (t0.5) was approximately 180 min.Attorney Docket No.11196-120WO1 Figure 1E shows the structural characterization of Cy5-conjugated fibrin using confocal microscopy (red) and SEM. Scale bars in the confocal microscopy images: top, 200 µm; bottom, 50 µm. Scale bars in SEM images: top, 5 µm; bottom, 1 µm. Figure 1F shows the characterization of the crosslinked fibrin-alginate-polylysine matrix. Representative images at a single confocal plane are shown. Alginate and polylysine were labeled with FAM and Cy3, respectively. Scale bars in SEM images: top, 5 µm; bottom, 1 µm. Scale bar in the confocal microscopy image: 200 µm. Figures 2A, 2B, 2C, 2D, 2E, 2F, 2G, and 2H shows results from examination of BZP development. Figure 2A shows confocal microscopy images showing step-by-step BZP development on the microparticle surface. Fibrin, alginate, and polylysine were labeled with Cy5, FAM, and Cy3, respectively, for observation. Figure 2B shows the assessment of development uniformity by imaging BZP on a confocal plane. Three lines were drawn at 0 °, 45 °, and 90 ° to analyze the distribution of fluorescence intensity on the perimeter of the BZP. Scale bar: 100 µm. Figure 2C shows confocal microscopy images of BZP captured in the x-y, y-z, and x-z projections. Three-dimensional Z-stack images were constructed to demonstrate development uniformity and completeness. Scale bars: 100 µm. Figure 3D shows confocal microscopy images of BZP developed on three microparticles of different sizes (45 µm, 100 µm, and 200 µm). Scale bar: 500 µm. Figure 3E shows confocal microscopy images of BZP developed on homotypic MSC spheroids and MCF7 spheroids. Top scale bars: 200 µm; bottom scale bars: 100 µm. Figure 3F shows confocal microscopy images of BZP developed on heterotypic MSC: HUVEC spheroids and MDA-MB231:3T3 spheroids. Top scale bars: 200 µm; bottom scale bars: 100 µm. Figure 3G shows confocal microscopy images of BZP developed on MSC spheroids with irregular shapes and geometries. Scale bar: 200 µm. Figure 3H shows confocal microscopy images of BZP developed on rat islets. Left scale bar: 200 µm, right scale bar: 100 µm. Figures 3A, 3B, 3C, 3D, 3E, and 3F characterize BZP permeability, spheroid stability, and cell bioactivity. Figure 3A assesses dextran penetration into cell spheroids with or without BZP. The spheroids were incubated with FITC–dextran with four different molecular weights (4 kDa, 20 kDa, 70 kDa, and 250 kDa) for 2 hours at room temperature and then imaged using a confocal microscope. Scale bar: 200 µm. Figure 3B examines MSC spheroid spreading on the substrate with or without BZP. Cell spheroids were incubated in a cell culture plate at 37oC for 72 h, gently stained with 1 µM calcein-AM for 30 min at 37°C, and finally imaged using a fluorescence microscope. Scale bar: 200 µm. Figure 3C shows the effect of the vortex on spheroid morphology. Uncoated and BZP-coated MSC spheroids were vortexed for 60 seconds before fluorescence imaging. Scale bar: 500 µm. Figure 3D examines cell viability using live / dead staining, ATP analysis, and metabolic activity. Live and dead cells were stained withAttorney Docket No.11196-120WO1 calcein AM (green) and EthD-1 (red), respectively, for confocal microscopy imaging of uncoated (left) and BZP-coated (right) MSC spheroids. Scale bar: 200 µm. Figure 3E shows a heatmap of human cytokines from native and BZP-coated MSC spheroids. Figure 3F shows VEGF secretion from uncoated and BZP-coated spheroids examined using ELISA. (ns: nonsignificant) Figures 4A, 4B, 4C, 4D, 4E, 4F, 4G, 4H, 4I, 4J, and 4K show in vivo evaluation of sustained glycemic control through intraperitoneal transplantation of rat islets in immunocompetent diabetic mice. Figure 4A shows a schematic outline of the animal study on foreign body reaction. Naked and BZP-coated microparticles were transplanted to the intraperitoneal cavity of mice on day 0 (D0). Intraperitoneal fluids were collected at D1 and D7 to analyze TNF-^, IL-6, TGF-^1, and IL-10. Figure 4B shows the inflammatory cytokine expression at D1 and D7 post-transplantation. The results were normalized relative to the cytokine levels of untreated mice. (n = 3, ns: nonsignificant, *P < 0.05, **P < 0.01, and ***P < 0.001). Figure 4C shows confocal microscopic images of uncoated (left) and BZP-coated (right) rat islets. Live and dead cells were stained with calcein AM (green) and EthD-1 (red), respectively. Nuclei were stained with Hoechst 33342 (blue). Scale bar: 100 µm. Figure 4D shows glucose-stimulated insulin secretion (GSIS) of rat islets. Islets were sequentially incubated in four glucose solutions, including L1 (2.8 mM glucose), H (16.7 mM glucose), L2 (2.8 mM glucose), and KCl (2.8 mM glucose and 30 mM KCl). The stimulation index was calculated as H / L1, and the delta was calculated as H-L1. (n = 4 and ns: nonsignificant). Figure 4E shows a schematic outline of the animal study on restoring normoglycemia in an STZ-induced diabetic BALB / c mouse model. Rat islets were transplanted into the peritoneal cavity at postoperative day 0 (POD 0). Figure 4F shows examination of IPGTT conducted on POD 60. (n = 5 for uncoated group; n = 4 for BZP- coated group). Figure 4G shows area under curve of the IPGTT profiles on POD 60 were calculated. (**P < 0.01). Figure 4H shows stimulated serum rat C-peptide concentrations of mice after glucose injection (0 min and 30 min) on POD 60 during the IPGTT experiment. (ns: nonsignificant and *P < 0.05). Figure 4I shows the average daily blood glucose readings from all groups. A horizontal shade was drawn between 200 mg / dL and 250 mg / dL to indicate normoglycemia. One mouse in the coated group, which developed hyperglycemia, was removed from the average profile at day 30 (shown in black arrow) (n, number of mice in each group). Figure 4J compares the AUC calculated from the overall blood glucose profiles up to POD 60. (***P < 0.001). Figure 4K shows the percentage of mice with normoglycemia after islet transplantation. (n = 5 in each group). Figure 4L shows the body weights of mice. Figure 4M shows the survival of mice. (n = 5 for healthy group, n = 7 for diabetic group, n = 5 for uncoated islets group, and n = 5 for BZP-coated islets group). Figures 5A and 5B examine aptamer-thrombin binding and aptamer-bound thrombinAttorney Docket No.11196-120WO1 activity. Figure 5A shows an electrophoretic mobility shift assay for examining the binding of DNA aptamers (Apt) to thrombin (Th). Polyacrylamide gel electrophoresis (12%) was run at 90 V for 45 min. SYBR gold was used to stain the DNA aptamers. The fluorescence intensity of thrombin-bound aptamers (red dotted box) and free aptamers was shown in proportional percentage to the total fluorescence intensity. Figure 5B shows the proteolytic activities of thrombin after binding to the aptamer. After incubation with aptamers (Apt-1, Apt-2, or Apt-3), thrombin activities were analyzed using a thrombin activity fluorometric kit. (ns: nonsignificant, **P < 0.01, and ***P < 0.001). Figures 6A, 6B, 6C, 6D, and 6E evaluate alginate diffusion and conjugation with fibrinogen. Figure 6A shows the simulation of one-dimensional alginate diffusion into a fibrin hydrogel using COMSOL Multiphysics v.6.0. At time 0, the alginate concentration of the bulk solution was 25 µM, and the alginate concentration of the fibrin hydrogel was zero. The bottom layer was assumed to be impermeable. The diffusion coefficient of alginate was set as 10-8cm² / s. Figure 6B shows the experimental determination of alginate diffusion into the fibrin hydrogel. The fibrin hydrogel (10 mg / mL) was incubated in an alginate-AF488 solution (0.25% w / v) for 1 hour. Fluorescence images show the vertical cross-sections of the bulk hydrogels. Figure 6C shows a gel electrophoresis image for characterizing the chemical conjugation of fibrinogen and alginate. Lane 1: Cy5 labeled fibrinogen, lane 2: AF488 labeled alginate-azide, lane 3: alginate- azide mixed with Cy5-labeled fibrinogen, lane 4: alginate- azide mixed with fibrinogen-DBCO without further incubation, lane 5: alginate-azide mixed with fibrinogen without further incubation, lane 6: alginate-azide mixed with Cy5-labeled fibrinogen after 60 min of incubation, lane 7: alginate-azide mixed with fibrinogen-DBCO after 60 min of incubation. Figure 6D shows the characterization of rheological behaviors of the fibrin matrix before and after hardening. Storage modulus G’ and loss modulus G’’ plots were acquired from the amplitude sweep test and frequency sweep test. This amplitude varied from 1.0% to 50% strain at a frequency of 1.0 rad s-1. Figure 6E shows SEM images of fibrin hydrogel, fibrin-alginate hydrogel, and crosslinked fibrin-alginate-polylysine matrix. Fibrin-alginate hydrogel was prepared by crosslinking alginate molecules in fibrin hydrogel with 50 mM CaCl2 solution. A crosslinked fibrin-alginate- polylysine matrix was prepared by further crosslinking alginate molecules in fibrin hydrogel with CaCl2 (50 mM) and polylysine (0.05% w / v) solution. Scale bars in SEM images: top, 5 µm; bottom, 1 µm. Figures 7A, 7B, and 7C show the aptamer display on the microparticle surface. Figure 7A shows the effect of incubation time on aptamer display. Microparticles (200 µm) were incubated with the aptamer solution (1 µM) for 1 to 30 minutes. After washing, the microparticles were incubated with the solution of FAM-labeled complementary sequence (1 µM) and examinedAttorney Docket No.11196-120WO1 using confocal microscopy. Figure 7B shows the effect of aptamer concentration on aptamer display. Microparticles were incubated with different concentrations of aptamer for 15 minutes. After washing, the microparticles were incubated with the solution of FAM-labeled complementary sequence (1 µM) and examined using confocal microscopy. Figure 7C shows the relationships of aptamer concentration used to treat the microparticles, number of decorated DNA aptamers, and the amount of immobilized thrombin density. The aptamers displayed were quantified using the fluorescently labeled complementary sequence with a standard curve using fluorescence intensity. The immobilized thrombin density was calculated by measuring the amount of unloaded thrombin in the supernatant. Figures 8A, 8B, 8C, 8D, 8E, 8F, and 8G characterize fibrin formation, alginate adsorption, and surface charge on the microparticle surface. Figure 8A shows fluorescence microscopy images of microparticles. Three different aptamers were displayed on the microparticle surface. The microparticles (200 µm) were incubated with thrombin solution (1 U / mL) for thrombin display on the surface. After washing, Cy5-labeled fibrinogen solution (10 mg / mL) was added and incubated for 10 min to form fibrin on the microparticle surface. Fluorescence images were obtained using the Olympus IX73 inverted microscope. Scale bar: 200 µm. (ns: nonsignificant and ***P < 0.001). Figure 8B shows flow cytometry analysis of fibrin-coated microparticles (5 µm). Aptamer-displayed microparticles were incubated with Cy5-conjugated fibrinogen (10 mg / mL) for 1 min at 37oC. The intensity values of the Apt-directed group and the untreated group were 24007 and 76, respectively. Figure 8C shows confocal microscopy images of fibrin- coated microparticles in three projections. Scale bar: 100 µm. Figure 8D shows confocal microscopy images showing the effect of fibrinogen concentration on coating completeness on the microparticle (200 µm) surface. Fibrinogen concentration was varied from 1 mg / mL to 10 mg / mL. Scale bar: 200 µm. Figure 8E shows the effect of incubation time on alginate penetration and adsorption in fibrin on the microparticle surface. Figure 8F shows confocal microscopic images showing step-by-step BZP development on the microparticle surface. Fibrin, alginate, and polylysine were labeled with Cy5, FAM, and Cy3, respectively, for observation. Scale bar: 500 µm. Figure 8G shows a Zeta potential analysis of microparticles (5 µm) to demonstrate the step- by-step BZP synthesis on the microparticle surface. Fb: fibrin. Fb / Al: fibrin-coated microparticles treated with alginate. Fb / Al / PLL: fibrin / alginate-coated microparticles treatedwith polylysine / CaCl2. Fb / Al / PLL / Al:fibrin / alginate / PLL-coated microparticles treated withalginate. Figure 8H shows the average Cy3 fluorescence profile of randomly chosen 65 BZP- coated microparticles. Figure 8I shows confocal microscopy images of BZP developed on three different sizes (50 µm, 100 µm, and 200 µm) of microparticles. Scale bars: 500 µm. Figures 9A, 9B, 9C, and 9D examine BZP formation on the surface of MSC spheroidsAttorney Docket No.11196-120WO1 and islets. Figure 9A shows phase contrast images of uncoated and BZP-coated MSC spheroids. The thickness of the BZP coating was measured from three different areas of each spheroid using ImageJ software. Scale bars: 100 µm. Figure 9B shows confocal microscopy images of BZP- coated MSC spheroids. Cy5-labeled fibrinogen, AF488-labeled alginate, and Cy3-labeled polylysine were used for imaging purposes. Figure 9C shows the examination of islets isolated from CD Sprague-Dawley rats. Pancreatic islets were chosen as a model for naturally heterotypic cell clusters. Phase contrast microscopy images of naked and dithizone-stained islets to show islet purity. Confocal microscopy images of BZP-coated islets. Cy5-labeled fibrinogen, AF488-labeled alginate, and Cy3-labeled polylysine were used for imaging. Scale bars: 200 µm. Figure 10 shows a comparison of uncoated and BZP-coated MSC spheroids in osteogenesis, chondrogenesis, and adipogenesis. Untreated MSC spheroids and BZP-coated spheroids were incubated in the corresponding differentiation medium in a 6-well plate for 21days. For the osteogenic potentialanalysis, cells were stained with Alizarin Red S solution (2% inDI H2O). For the chondrogenic potential analysis, cells were stained with Alcian Blue solution(1% in 3% acetic acid). For theadipogenic potential analysis, cells were stained with Oil Red Osolution (0.3% in DI H2O). Images were obtained using inverted phase contrast microscopy. Scale bars: 100 µm. Figure 11 shows the volume ratio of microcapsule to BZP coating. The diameter of cell spheroids was varied from 100 µm to 200 µm. The diameter of traditional microcapsules varied from 500 µm to 1000 µm. BZP coating thickness was set as 20 µm. Polymer volumes were calculated by subtracting the core cell spheroid’s volume from the total volume of encapsulated or BZP-coated spheroids. The polymer volume ratio was calculated by dividing the volume of microcapsules by the volume of BZP. Figures 12A and 12B examines BZP in immunoisolation. Figure 12A shows MCF7 spheroids were co-cultured with NK-92MI cells in complete growth medium at 37oC for 24 hours. MCF7 spheroids were stained with CFSE (green), and NK-92MI cells were stained with CellTrace Far Red dye (red). Scale bars: 200 µm. Untreated spheroids are native ones without BZP. Figure 12B shows naked and BZP-coated rat pancreatic islets were incubated in complete growth media supplemented with IL-1^ (5 ng / mL), TNF-^ (10 ng / mL), and IFN-^ (100 ng / mL) for 24 h. Pancreatic islets were dissociated into single cells before performing an apoptosis assay using the Annexin V-FITC Apoptosis Detection Kit. Cell populations in Q2 and Q3 were added for comparison. Figures 13A, 13B, 13C, 13D, 13E, and 13F show DNA hybridization for enzyme display on the cell surface for encapsulation. Figure 13A shows flow cytometric analysis of bovine serum albumin (BSA) displayed by DNA-cDNA hybridization. Cholesterol-DNA is inserted intoAttorney Docket No.11196-120WO1 the lipid bilayer, and cDNA-protein conjugate is displayed by hybridizing with cholesterol-DNA. cDNA: complementary DNA. BSA was conjugated with FITC for fluorescence observation. The graph shows the DNA concentration-dependent fluorescence intensity. Figure 13B shows a confocal microscopic image of a mesenchymal stem cell with FITC-BSA decorated on the surface. Figure 13C shows the half-life of decorated BSA on the mesenchymal stem cell surface. Figure 13D shows flow cytometric analysis of the fibrin coating signal on the cell surface. Cholesterol-DNA, cDNA-thrombin, and Cy5-labeled fibrinogen were used for fluorescence analysis. Figure 13E shows a confocal microscopic image of a mesenchymal stem cell with fibrin coating on the surface. Figure 13F shows a confocal microscopic image of a mesenchymal stem cell spheroid with fibrin coating on the surface. Figures 14A, 14B, 14C, 14D, and 14E show the in vivo evaluation of sustained glycemic control through renal subcapsular transplantation of allogeneic islets in immunocompetent diabetic mice. Figure 14A shows an assessment of the intraperitoneal glucose tolerance test (IPGTT) conducted on POD 40. (n = 5 for BZP-U group and n = 7 for BZP-M group). Figure 14B shows the AUC of the IPGTT profiles. (*P < 0.05). Figure 14C shows stimulated serum mouse C-peptide measurements before and after glucose injection (0 min and 30 min) on POD 20 during the IPGTT experiment. (***P < 0.001). Figure 14D shows the percentage of mice with normoglycemia. The p-value was obtained by analyzing survival curves using the log-rank (Mantel-Cox) test. (**P < 0.01). Figure 14E shows individual blood glucose profiles of both groups with a horizontal shade drawn between 200 mg / dL and 250 mg / dL to indicate normoglycemia. Figures 15A, 15B, 15C, and 15D shows permeability assay results. Figure 1A examines FITC-dextran penetration into uncoated, Fb-coated, and BZP-coated MSC spheroids. Cell spheroids were incubated in FITC–dextran solution with four different molecular weights (4 kDa, 20 kDa, 70 kDa, or 250 kDa) for 2 hours at room temperature and then imaged using Zeiss LSM 880 confocal microscopy. Scale bar: 200 µm. Figure 15B shows assessment of FITC- dextran diffusion into bulk Fb hydrogel and Fb / Al / PLL hydrogel. Hydrogels were incubated in FITC–dextran solutions (4 kDa, 20 kDa, 70 kDa, and 250 kDa) at room temperature and then imaged using CRI Maestro EX System. Scale bars: 1 mm. Figure 15C shows the diffusion profiles of FITC-dextran (4 kDa, 20 kDa, 70 kDa, and 250 kDa) across control (untreated), Fb matrix, Fb / Al, and Fb / Al / PLL coating on a Transwell system. Solutions from basolateral side were collected at predetermined time points and fluorescence intensities were analyzed using a multimode microplate reader. Figure 15D shows the assessment of molecular transport across BZP. Flow cytometric analysis and confocal microscopic images after treating with FITC-labeled antibodies. Scale bar: 200 ^m.Attorney Docket No.11196-120WO1 Figure 16 shows calculated graft volumes of BZP coating and alginate microcapsules. The diameter of alginate microcapsules for islet transplantation varied from 0.5 mm to 1.5 mm for encapsulating 150 µm diameter islets. BZP coating thickness was set as 0.02 mm. Graft volumes were calculated by assuming one patient needs a dose of one million islets. Three islets were assumed to be encapsulated in one microcapsule for the 1.5 mm diameter alginate microcapsule. Figures 17A, 17B, 17C, 17D, and 17E show the synthesis and examination of BZP-M. Figure 17A shows1H NMR characterization of zwitterionic sulfobetaine modified alginate. UP- alginate: ultrapure alginate. M-alginate: zwitterionic sulfobetaine modified ultrapure alginate. Figure 17B shows adsorption of FITC-BSA and FITC-lysozyme on the surfaces of BZP-U (BZP synthesized using unmodified regular alginate), BZP-UP (BZP synthesized using UP-alginate), or BZP-M (BZP synthesized using M-alginate). The fluorescence intensities were normalized to BZP-U samples. (***P < 0.001). Figure 17C shows the level of TGF-^1 on day 7 post- transplantation. Mice were intraperitoneally transplanted with either BZP-U or BZP-M modified microparticles. (n = 4 and *P < 0.05). Figure 17D shows phase contrast microscopic images of dithizone-stained islets for showing islet purity. Scale bars: 200 µm. Figure 17E shows SEM micrographs of uncoated and BZP-coated islets. Scale bars: 50 µm. Figures 18A and 18B show the transplantation of allogeneic islets in BALB / c mice. Figure 18A shows daily blood glucose measurements from mice treated with islets. Mice developing hyperglycemia were removed from the average profile at POD 60 and POD 99 (shown in black arrow). (n = 5 for BZP-U group and n = 7 for BZP-M group). Figure 18B shows AUC calculated from the daily blood glucose profiles up to POD 60. (*P < 0.05) DETAILED DESCRIPTION Drawing inspiration from the zona pellucida (ZP) of the human egg, the inventors have developed a novel method for conformally coating cells. The methods described herein are improved over the state of the art coating methods in that they demonstrate the possibility of creating higher-order complex cellular structures or compartments in aqueous solutions under physiological conditions with little reliance on external tools. Terminology In this specification and in the claims which follow, reference will be made to a number of terms which shall be defined to have the following meanings:Attorney Docket No.11196-120WO1 As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a pharmaceutical carrier” includes mixtures of two or more such carriers, and the like. Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. 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 value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value “10” is disclosed the “less than or equal to 10”as well as “greater than or equal to 10” is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point 15 are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed. “Optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. An "increase" can refer to any change that results in a greater amount of a symptom, disease, composition, condition, or activity. An increase can be any individual, median, or average increase in a condition, symptom, activity, composition in a statistically significant amount. Thus, the increase can be a 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100% increase so long as the increase is statistically significant.Attorney Docket No.11196-120WO1 A "decrease" can refer to any change that results in a smaller amount of a symptom, disease, composition, condition, or activity. A substance is also understood to decrease the genetic output of a gene when the genetic output of the gene product with the substance is less relative to the output of the gene product without the substance. Also, for example, a decrease can be a change in the symptoms of a disorder such that the symptoms are less than previously observed. A decrease can be any individual, median, or average decrease in a condition, symptom, activity, composition in a statistically significant amount. Thus, the decrease can be a 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100% decrease so long as the decrease is statistically significant. "Inhibit," "inhibiting," and "inhibition" mean to decrease an activity, response, condition, disease, or other biological parameter. This can include but is not limited to the complete ablation of the activity, response, condition, or disease. This may also include, for example, a 10% reduction in the activity, response, condition, or disease as compared to the native or control level. Thus, the reduction can be a 10, 20, 30, 40, 50, 60, 70, 80, 90, 100%, or any amount of reduction in between as compared to native or control levels. By “reduce” or other forms of the word, such as “reducing” or “reduction,” is meant lowering of an event or characteristic (e.g., tumor growth). It is understood that this is typically in relation to some standard or expected value, in other words it is relative, but that it is not always necessary for the standard or relative value to be referred to. For example, “reduces tumor growth” means reducing the rate of growth of a tumor relative to a standard or a control. By “prevent” or other forms of the word, such as “preventing” or “prevention,” is meant to stop a particular event or characteristic, to stabilize or delay the development or progression of a particular event or characteristic, or to minimize the chances that a particular event or characteristic will occur. Prevent does not require comparison to a control as it is typically more absolute than, for example, reduce. As used herein, something could be reduced but not prevented, but something that is reduced could also be prevented. Likewise, something could be prevented but not reduced, but something that is prevented could also be reduced. It is understood that where reduce or prevent are used, unless specifically indicated otherwise, the use of the other word is also expressly disclosed. The term “subject” refers to any individual who is the target of administration or treatment. The subject can be a vertebrate, for example, a mammal. In one aspect, the subject can be human, non-human primate, bovine, equine, porcine, canine, or feline. The subject can also be a guinea pig, rat, hamster, rabbit, mouse, or mole. Thus, the subject can be a human or veterinary patient. The term “patient” refers to a subject under the treatment of a clinician, e.g., physician. The term “subject” may be used interchangeably with the terms “individual” andAttorney Docket No.11196-120WO1 “patient” and includes human and non-human mammalian subjects. In embodiments, the subject has type 1 diabetes. Administering the BZP-coated pancreatic islet cell may treat diabetes in the subject. The term “therapeutically effective” refers to the amount of the composition used is of sufficient quantity to ameliorate one or more causes or symptoms of a disease or disorder. Such amelioration only requires a reduction or alteration, not necessarily elimination. The term “treatment” refers to the medical management of a patient with the intent to cure, ameliorate, stabilize, or prevent a disease, pathological condition, or disorder. This term includes active treatment, that is, treatment directed specifically toward the improvement of a disease, pathological condition, or disorder, and also includes causal treatment, that is, treatment directed toward removal of the cause of the associated disease, pathological condition, or disorder. In addition, this term includes palliative treatment, that is, treatment designed for the relief of symptoms rather than the curing of the disease, pathological condition, or disorder; preventative treatment, that is, treatment directed to minimizing or partially or completely inhibiting the development of the associated disease, pathological condition, or disorder; and supportive treatment, that is, treatment employed to supplement another specific therapy directed toward the improvement of the associated disease, pathological condition, or disorder. "Comprising" is intended to mean that the compositions, methods, etc. include the recited elements, but do not exclude others. "Consisting essentially of'' when used to define compositions and methods, shall mean including the recited elements, but excluding other elements of any essential significance to the combination. Thus, a composition consisting essentially of the elements as defined herein would not exclude trace contaminants from the isolation and purification method and pharmaceutically acceptable carriers, such as phosphate buffered saline, preservatives, and the like. "Consisting of'' shall mean excluding more than trace elements of other ingredients and substantial method steps for administering the compositions provided and / or claimed in this disclosure. Embodiments defined by each of these transition terms are within the scope of this disclosure. A “control” is an alternative subject or sample used in an experiment for comparison purposes. A control can be "positive" or "negative." As used herein, “enhance”, “enhanced”, “enhancement”, “enhancing”, and any grammatical variations thereof as used herein, refers to an act of intensifying, increasing, or further improving the quality, value, or extent of a biological function, composition, compound, cell, or tissue. As used herein, “diagnose”, “diagnosed”, “diagnosing”, and any grammatical variations thereof as used herein, refers to the act of process of identifying the nature of an illness, disease,Attorney Docket No.11196-120WO1 disorder, or condition in a subject by examination or monitoring of symptoms. A biomimetic zona pellucida (BZP) is a substance developed ex vivo that structurally mimics the zona pellucida of the mammalian oocyte (egg). A BZP, as described herein, comprises a fibrin-alginate hydrogel. The terms “coating”, “conformally coating”, and “encapsulating” are used herein interchangeably to refer to the process of applying a substance to a surface in a substantially uniform manner. A “coated”, “conformally coated”, or “encapsulated” cell, spheroid, or particle has a substantially uniform coating around it. The coating may be substantially uniform in thickness and composition. In embodiments, the coating process results in a BZP thickness of between about 10 ^M and about 30 ^M. In exemplary embodiments, the coating process results in a BZP thickness of about 20 ^M. As used herein, the term "administering", refers to dispensing, delivering, or applying the BZP-coated islet cells, to a subject by any suitable route for delivery of the inhibitor to the desired location in the subject, including delivery by the parenteral route, transplantation, intramuscular injection, subcutaneous / intradermal injection, intravenous injection, and intraperitoneal injection. In preferred embodiments, the BZP-coated islet cells are administered to the subject by transplantation into the liver. The method may comprise administering a therapeutically effective amount of the BZP- coated islet cells to the subject. The terms "effective amount" or “therapeutically effective amount” refer to an amount sufficient to effect beneficial or desirable biological and / or clinical results. The amount of the agent or pharmaceutical composition that is therapeutically effective may vary depending on the particular condition of the subject. Appropriate dosages may be determined, for example, by extrapolation from cell culture assays, animal studies, or human clinical trials taking into account body weight of the patient, absorption rate, half-life, disease severity and the like. The dosage lies preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. A dose can be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography. As used herein, the terms “protein” or “polypeptide” or “peptide” may be used interchangeable to refer to a polymer of amino acids. Typically, a “polypeptide” or “protein” is defined as a longer polymer of amino acids, of a length typically of greater than 50, 60, 70, 80, 90, or 100 amino acids. A “peptide” is defined as a short polymer of amino acids, of a length typicallyAttorney Docket No.11196-120WO1 of 50, 40, 30, 20 or less amino acids. A protein typically comprises a polymer of naturally or non- naturally occurring amino acids (e.g., alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine). The terms “nucleic acid” and “nucleic acid molecule,” as used herein, refer to a compound comprising a nucleobase and an acidic moiety, e.g., a nucleoside, a nucleotide, or a polymer of nucleotides. Nucleic acids generally refer to polymers comprising nucleotides or nucleotide analogs joined together through backbone linkages, such as but not limited to phosphodiester bonds. Nucleic acids include deoxyribonucleic acids (DNA) and ribonucleic acids (RNA), such as messenger RNA (mRNA), transfer RNA (tRNA), etc. Typically, polymeric nucleic acids, e.g., nucleic acid molecules comprising three or more nucleotides, are linear molecules, in which adjacent nucleotides are linked to each other via a phosphodiester linkage. As used herein, the terms “oligonucleotide” and “polynucleotide” can be used interchangeably to refer to a polymer of nucleotides (e.g., a string of at least three nucleotides). Nucleic acids encompass RNA as well as single and / or double-stranded DNA. Nucleic acids may be naturally occurring, for example, in the context of a genome, a transcript, an mRNA, tRNA, rRNA, siRNA, snRNA, a plasmid, cosmid, chromosome, chromatid, or other naturally occurring nucleic acid molecule. On the other hand, a nucleic acid molecule may be a non-naturally occurring molecule, e.g., a recombinant DNA or RNA, an artificial chromosome, an engineered genome, or a fragment thereof, or a synthetic DNA, RNA, DNA / RNA hybrid, or include non-naturally occurring nucleotides or nucleosides. Furthermore, the terms “nucleic acid,” “DNA,” “RNA,” and / or similar terms include nucleic acid analogs, i.e., analogs having a backbone other than a phosphodiester backbone. Nucleic acids can be purified from natural sources, produced using recombinant expression systems, and optionally purified, chemically synthesized, etc. Where appropriate, e.g., in the case of chemically synthesized molecules, nucleic acids can comprise nucleoside analogs such as analogs having chemically modified bases or sugars, and backbone modifications. A nucleic acid sequence is presented in the 5^ to 3^ direction unless otherwise indicated. In some embodiments, a nucleic acid is or comprises natural nucleosides (e.g. adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxyguanosine, and deoxycytidine); nucleoside analogs (e.g., 2- aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3-methyl adenosine, 5- methylcytidine, 2-aminoadenosine, C5-bromouridine, C5-fluorouridine, C5- iodouridine, C5- propynyl-uridine, C5-propynyl-cytidine, C5-methylcytidine, 2-aminoadeno sine, 7- deazaadenosine, 7-deazaguanosine, 8-oxoadenosine, 8-oxoguanosine, O(6)- methylguanine, and 2- thiocytidine); chemically modified bases; biologically modified bases (e.g., methylated bases); intercalated bases; modified sugars (e.g., 2^-fluororibose, ribose, 2^-Attorney Docket No.11196-120WO1 deoxyribose, arabinose, and hexose); and / or modified phosphate groups (e.g., phosphorothioates and 5^-N-phosphoramidite linkages). “Recombinant polynucleotide” refers to a polynucleotide having sequences that are not naturally joined together. An amplified or assembled recombinant polynucleotide may be included in a suitable vector, and the vector can be used to transform a suitable host cell. A recombinant polynucleotide may serve a non-coding function (e.g., promoter, origin of replication, ribosome- binding site, etc.) as well. References in the specification to "one embodiment," "an embodiment," etc., indicate that the embodiment described may include a particular aspect, feature, structure, moiety, or characteristic, but not every embodiment necessarily includes that aspect, feature, structure, moiety, or characteristic. Moreover, such phrases may, but do not necessarily, refer to the same embodiment referred to in other portions of the specification. Further, when a particular aspect, feature, structure, moiety, or characteristic is described in connection with an embodiment, it is within the knowledge of one skilled in the art to affect or connect such aspect, feature, structure, moiety, or characteristic with other embodiments, whether or not explicitly described. As used herein, “substantially” and “significantly” will be understood by persons of ordinary skill in the art and will vary to some extent depending on the context in which they are used. If there are uses of the term which are not clear to persons of ordinary skill in the art, given the context in which it is used, “substantially” and “significantly” will mean plus or minus >10% of the particular term. The term "and / or" means any one of the items, any combination of the items, or all of the items with which this term is associated. The phrase "one or more" is readily understood by one of skill in the art, particularly when read in the context of its usage. For example, one or more substituents on a phenyl ring refers to one to five, or one to four, for example, if the phenyl ring is di-substituted. As used herein, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating a listing of items, “and / or” or “or” shall be interpreted as being inclusive, e.g., the inclusion of at least one, but also including more than one of a number of items, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of” or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e., “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” As used herein, the terms “including,” “includes,” “having,” “has,” “with,” or variantsAttorney Docket No.11196-120WO1 thereof, are intended to be inclusive, similar to the term “comprising.” The term "about" can refer to a variation of ± 5%, ± 10%, ± 20%, or ± 25% of the specified value. For example, "about 50" percent can carry a variation from 45 to 55 percent in some embodiments. For integer ranges, the term "about" can include one or two integers greater than and / or less than a recited integer at each end of the range. Unless indicated otherwise herein, the term "about" is intended to include values, e.g., weight percentages, proximate to the recited range that are equivalent in terms of the functionality of the individual ingredient, the composition, or the embodiment. The term about can also modify the endpoints of a recited range as discussed above in this paragraph. The term "substantial identity'' or "substantial similarity" of polynucleotide or peptide sequences means that a polynucleotide or peptide comprises a sequence that has at least 75% sequence identity. Alternatively, percent identity can be any integer from 75% to 100%. More preferred embodiments include at least: 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% compared to a reference sequence using the programs described herein; preferably BLAST using standard parameters, as described. These values can be appropriately adjusted to determine the corresponding identity of proteins encoded by two nucleotide sequences by taking into account codon degeneracy, amino acid similarity, reading frame positioning, and the like. The determination of percent identity between two nucleotide or amino acid sequences can be accomplished using a mathematical algorithm. For example, a mathematical algorithm useful for comparing two sequences is the algorithm of Karlin and Altschul (1990, Proc. Natl. Acad. Sci. USA 87:2264-2268), modified as in Karlin and Altschul (1993, Proc. Natl. Acad. Sci. USA 90:5873-5877). This algorithm is incorporated into the NBLAST and XBLAST programs of Altschul, et al. (1990, J. Mol. Biol.215:403-410), and can be accessed, for example at the National Center for Biotechnology Information (NCBI) world wide web site having the universal resource locator using the BLAST tool at the NCBI website. BLAST nucleotide searches can be performed with the NBLAST program (designated “blastn” at the NCBI web site), using the following parameters: gap penalty = 5; gap extension penalty = 2; mismatch penalty = 3; match reward = 1; expectation value 10.0; and word size = 11 to obtain nucleotide sequences homologous to a nucleic acid described herein. BLAST protein searches can be performed with the XBLAST program (designated “blastn” at the NCBI web site) or the NCBI “blastp” program, using the following parameters: expectation value 10.0, BLOSUM62 scoring matrix to obtain amino acid sequences homologous to a protein molecule described herein. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al. (1997, Nucleic Acids Res. 25:3389-3402). Alternatively, PSI-Blast or PHI-Blast can be used to perform an iterated searchAttorney Docket No.11196-120WO1 which detects distant relationships between molecules (Id.) and relationships between molecules which share a common pattern. When utilizing BLAST, Gapped BLAST, PSI-Blast, and PHI- Blast programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used. The percent identity between two sequences can be determined using techniques similar to those described above, with or without allowing gaps. In calculating percent identity, typically, exact matches are counted. As used herein, a “hydrogel” refers to a three-dimensional polymer network to imbibe large amounts of water, which is used for the purpose of biomedical applications, including but not limited to: treatment of wound healing, cell culture, drug delivery, contact lenses, plastic surgery, and tissue regeneration. Hydrogels can chemically or physically contain various pharmaceutical drugs or immunomodulatory agents, including chemical drugs, proteins, peptides, nucleotides, and ions. Hydrogels also enable control of responses by modulation of the density and polarity of the polymer network, imparting the stimuli responsiveness to the polymer network. “Composition” refers to any agent that has a beneficial biological effect. Beneficial biological effects include both therapeutic effects, e.g., treatment of a disorder or other undesirable physiological condition, and prophylactic effects, e.g., prevention of a disorder or other undesirable physiological condition (e.g., diabetes). The terms also encompass pharmaceutically acceptable, pharmacologically active derivatives of beneficial agents specifically mentioned herein, including, but not limited to, a vector, polynucleotide, cells, salts, esters, amides, proagents, active metabolites, isomers, fragments, analogs, and the like. When the term “composition” is used, then, or when a particular composition is specifically identified, it is to be understood that the term includes the composition per se as well as pharmaceutically acceptable, pharmacologically active vector, polynucleotide, salts, esters, amides, proagents, conjugates, active metabolites, isomers, fragments, analogs, etc. In some aspects, the composition disclosed herein comprises a pancreatic islet cell coated with biomimetic zona pellucida (BZP). A “therapeutic composition” and / or “therapeutic agent” refers to at least one substance, molecule, or compound suitable for administering to a subject, wherein the composition further includes a pharmaceutical carrier. A non-limiting example includes a therapeutic composition that comprises a nucleobase-poly-amino acid carrier and a sterile water-based solution. As will be understood by the skilled artisan, all numbers, including those expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth, are approximations and are understood as being optionally modified in all instances by the term "about." These values can vary depending upon the desired properties sought to be obtained byAttorney Docket No.11196-120WO1 those skilled in the art, utilizing the teachings of the descriptions herein. It is also understood that such values inherently contain variability, necessarily resulting from the standard deviations found in their respective testing measurements. The term “standard” refers to something used for comparison. For example, it can be a known standard agent or compound that is administered and used for comparing results when administering a test compound, or it can be a standard parameter or function that is measured to obtain a control value when measuring the effect of an agent or compound on a parameter or function. Standard can also refer to an “internal standard”, such as an agent or compound which is added at known amounts to a sample and is useful in determining such things as purification or recovery rates when a sample is processed or subjected to purification or extraction procedures before a marker of interest is measured. Internal standards are often a purified marker of interest which has been labeled, such as with a radioactive isotope, allowing it to be distinguished from an endogenous marker. As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges recited herein also encompass any and all possible sub-ranges and combinations of sub-ranges thereof, as well as the individual values making up the range, particularly integer values. A recited range (e.g., weight percentages or carbon groups) includes each specific value, integer, decimal, or identity within the range. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, or tenths. As a non-limiting example, each range described herein can be readily broken down into a lower third, middle third, upper third, etc. As will also be understood by one skilled in the art, all language such as "up to," "at least," "greater than" "less than," "more than," "or more," and the like, include the number recited and such terms refer to ranges that can be subsequently broken down into sub-ranges as discussed above. For example, if a concentration range is stated as 1% to 50%, it is intended that values such as 2% to 40%, 10% to 30%, or 1% to 3%, etc., are expressly enumerated in this specification. In the same manner, all ratios recited herein also include all sub-ratios falling within the broader ratio. Accordingly, specific values recited for radicals, substituents, and ranges are for illustration only; they do not exclude other defined values or other values within defined ranges for radicals and substituents. One skilled in the art will also readily recognize that where members are grouped together in a common manner, such as in a Markush group, the invention encompasses not only the entire group listed as a whole, but each member of the group individually and all possible subgroups of the main group. Additionally, for all purposes, the invention encompasses not only the main group, but alsoAttorney Docket No.11196-120WO1 the main group absent one or more of the group members. The invention, therefore, envisages the explicit exclusion of any one or more of the members of a recited group. Accordingly, provisos may apply to any of the disclosed categories or embodiments whereby any one or more of the recited elements, species, or embodiments may be excluded from such categories or embodiments, for example, for use in an explicit negative limitation. Methods involving conventional molecular biology techniques are described herein. Such techniques are generally known in the art and are described in detail in methodology treatises, such as Molecular Cloning: A Laboratory Manual, 2nd ed., vol. 1-3, ed. Sambrook et al., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989; and Current Protocols in Molecular Biology, ed. Ausubel et al., Greene Publishing and Wiley-Interscience, New York, 1992 (with periodic updates). Methods for chemical synthesis of nucleic acids are discussed, for example, in Beaucage and Carruthers, Tetra. Letts. 22: 1859-1862, 1981, and Matteucci et al., J. Am. Chem. Soc.103:3185, 1981. Biomimetic zona pellucida-coated microparticle, cell, or therapeutic agent The zona pellucida is a thick, glycoprotein-rich extracellular matrix that surrounds the plasma membrane of mammalian oocytes (eggs). It plays a vital role in fertilization by mediating the initial binding of sperm to the egg and triggering the acrosome reaction, a process essential for sperm to penetrate the egg. The zona pellucida also protects the oocyte and early embryo during development and regulates species-specific fertilization, helping to prevent cross-species breeding. It is composed mainly of several glycoproteins, such as ZP1, ZP2, and ZP3, which create a complex, highly organized structure essential for physical protection and biological signaling during reproduction. Disclosed herein is a microparticle, cell, or therapeutic agent coated with biomimetic zona pellucida (BZP). The biomimetic zona pellucida (BZP) is an artificial or engineered version of the natural zona pellucida. This glycoprotein-rich matrix surrounds mammalian oocytes and plays a crucial role in fertilization. Designed to replicate the structure and function of the natural zona, the biomimetic version is typically created using purified native proteins, recombinant proteins, or synthetic materials that imitate the key binding and recognition properties of the real zona pellucida. A microparticle is a small particle with a diameter typically ranging from 1 micrometer (µm) to 1000 micrometers (1 mm) made up of a biocompatible material (such as, for example, polystyrene, poly(lactic-co-glycolic acid) (PLGA), silica, and agarose). In some embodiments, the microparticle or the cell is 10-100 ^m in diameter. In some embodiments, the microparticle is 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56,Attorney Docket No.11196-120WO1 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 ^m in diameter. In some embodiments, the cell is 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 ^m in diameter. Some exemplary biocompatible materials a microparticle can be made up of are Biodegradable Polymers (Common in Drug Delivery & Tissue Engineering): PLGA (poly(lactic- co-glycolic acid)), PLA (polylactic acid), PCL (polycaprolactone), Chitosan, Alginate, Gelatin, Collagen, Hyaluronic acid, Cellulose derivatives (e.g., HPMC); Synthetic / Non-biodegradable Polymers: Polystyrene, Poly(methyl methacrylate) (PMMA), Polyethylene glycol (PEG), Polyvinyl alcohol (PVA), Nylon, Polyurethane; Inorganic Materials: Silica (SiO^), Calcium phosphate / Hydroxyapatite, Magnetite (Fe^O^) – for magnetic microparticles, Gold or silver, Titanium dioxide (TiO^), Zinc oxide (ZnO); Lipids & Amphiphiles (in Microparticle Emulsions or Vesicles): Phospholipids (e.g., lecithin), Stearic acid, Cholesterol, Lipid-polymer hybrids; Natural / Biomimetic Materials: Starch, Dextran, albumin, Fibrinogen, Silk fibroin; Composite & Functional Materials: Magnetic particles coated with polymers or proteins, Polymer-ceramic composites, Polydopamine-coated cores, Core-shell particles (e.g., silica core with a PEG shell). In some embodiments, the biocompatible material is selected from Polystyrene, poly(lactic-co- glycolic acid) (PLGA), silica, and agarose. As described herein, the microparticle comprises a functionalized surface, and the BZP comprises a 3-dimensional (3D) polymer meshwork bound to the microparticle's functionalized surface, wherein the functionalized surface of the microparticle comprises an enzyme-binding molecule and an enzyme. Some examples of enzyme-binding molecules and the respective binding enzymes are Zona pellucida glycoproteins (substrate) which binds to enzyme, Arosin (in the acrosome) or Proacrosin, Hyaluronic acid which binds to enzyme hyaluronidase (e.g., PH-20) ZP proteins which bind to cathepsin-like proteases, extracellular matrix components that bind to Matrix Metalloproteinases (MMPs), plasminogen that binds to urokinase-type plasminogen activator (uPA), ubiquitinated proteins on the zona pellucida that can bind to sperm proteasome, ZP2 glycoprotein that binds to enzyme Ovastacin, L-tyrosine and L-DOPA (dihydroxyphenylalanine) which is a substrate for Tyrosinase, Glutamine residues in proteins (amine donor) and primary amines (amine acceptor, e.g., lysine) are a substrate for Transglutaminase, Hydrogen peroxide (H^O^) and electron donors (e.g., phenols, amines)are a substrate for Peroxidase, LPXTG motif- containing peptides and oligoglycine (nucleophile / acceptor)are substrates for Sortase (e.g.,Attorney Docket No.11196-120WO1 Sortase A), Hydrogen peroxide (H^O^) + chromogenic substrates (e.g., TMB, DAB, ABTS) are acted on by enzyme Horseradish Peroxidase (HRP), Phosphate monoesters (e.g., p-nitrophenyl phosphate — pNPP) are substrates for the enzyme, Alkaline Phosphatase (ALP), Starch is a substrate for Amylase, Peptides are substrates for Trypsin, DNA strand and nucleotides bind to DNA Polymerase, Acetylcholine is a substrate for Acetylcholinesterase, CO^ and H^O are substrates for Carbonic Anhydrase, Lactose is a substrate for Lactase, Glucose and ATP are substrates and co-substrates, respectively, for Hexokinase, specific peptide motifs are substrates for Caspase-3, Arachidonic acid is a substrate of Cyclooxygenase (COX-1 / COX-2), RNA template and nucleotides are substrates for Reverse Transcriptase. In some embodiments, the enzyme-binding molecule is streptavidin. In some embodiments, the enzyme-binding molecule is an aptamer that binds the enzyme. In some embodiments, the enzyme-binding molecule is a biotinylated DNA aptamer. In some embodiments, the enzyme-binding molecules are other aptamers, such as, for example, an anti-thrombin aptamer. In some embodiments, the enzyme- binding molecule is an anti-thrombin aptamer comprising a sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3. In exemplary embodiments, the anti-thrombin aptamer is Apt-1 (SEQ ID NO: 1), Apt-2 (SEQ ID NO: 2), or Apt-3 (SEQ ID NO: 3). In preferred embodiments, the anti-thrombin aptamer is Apt-2 (SEQ ID NO: 2). In some embodiments, the anti-thrombin aptamer comprises SEQ ID NO: 2. In other exemplary embodiments, the enzyme- binding molecule is a complementary DNA (cDNA) molecule, and the enzyme is conjugated to a DNA molecule, wherein the cDNA molecule and DNA molecule hybridize with each other, thereby joining the enzyme and enzyme-binding molecule. In some embodiments, the enzyme is selected from thrombin, tyrosinase, transglutaminase, peroxidase, sortase, horseradish peroxidase, and alkaline phosphatase. In some embodiments, the enzyme is a serine protease enzyme. In some embodiments, the serine protease enzyme is thrombin. In some embodiments, the enzyme is provided to the microparticle, cell or therapeutic agent at between about 0.1 U / mL and about 10 U / mL; in some cases, the enzyme is provided to the microparticle, cell or therapeutic agent at about 1 U / ml. In some embodiments, the enzyme is provided to the microparticle, cell or therapeutic agent at about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, or 10 U / mL. In some embodiments, the enzyme is provided to the microparticle, cell or therapeutic agent at about 1 U / ml. As disclosed herein, the BZP is 10 to 30 µm in thickness. In some embodiments, the BZPAttorney Docket No.11196-120WO1 is 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 µm in thickness. As disclosed herein, the BZP comprises a 3D polymer meshwork comprising a polymer coating crosslinked with one or more blending molecules in a blending solution. In some embodiments, the polymer coating comprises a coating molecule. Coating molecules (also called crosslinkers, anchoring agents, or polymerizable substrates) can bind enzymes and help form a polymer or functional coating on a surface. Coating molecules are often used in biomaterials, biosensors, and surface functionalization. Some exemplary coating molecules are DOPA / Dopamine, Fibrinogen, Gelatin / Casein / Collagen, Tyramine, Phenol- or aniline-derivatives, p-Aminophenylalanine-PEG, p-Nitrophenyl phosphate (pNPP), Acryloyl-PEG-NHS, Maleimide-functionalized PEG, and NHS-Activated Polymers. Tyrosinase oxidizes dopamine to form polydopamine, which is a universal adhesive coating. Fibrinogen is crosslinked by transglutaminase to form fibrin-like hydrogel networks. Gelatin / Casein / Collagen forms protein-based polymer films or scaffolds via crosslinking of glutamine and lysine residues in the presence of transglutaminase. HRP + H^O^ polymerize tyramine into adhesive hydrogels or surface coatings. Phenol- or aniline-derivatives are oxidatively polymerized into conductive or adhesive coatings (e.g., poly(phenol)) by peroxidase / laccase. p-Aminophenylalanine-PEG in the presence of Sortase A is covalently ligated to proteins with LPXTG motifs, which allows site-specific surface anchoring. Alkaline Phosphatase (ALP) cleaves p-Nitrophenyl phosphate (pNPP) to produce a colorimetric signal, which is sometimes used in signal amplification for bioactive coatings. Any enzyme with lysine residues reacts with amine groups on enzymes such as, for example, Acryloyl-PEG-NHS, to anchor them to polymerizing acrylate systems. Enzymes with thiol (-SH) groups use Maleimide- functionalized PEG as a substrate to form stable thioether linkages to covalently attach enzymes to surfaces or networks. NHS-Activated Polymers covalently bind any primary amine-containing enzyme to a polymer scaffold via amide bond formation. In some embodiments, the enzyme cleaves a coating molecule and assembles the polymer coating. In some embodiments, the coating molecule comprises fibrinogen, and the polymer coating is fibrin. Fibrinogen is a plasma glycoprotein converted enzymatically by thrombin to fibrin, forming a fibrin-based blood clot. Incubating the cell in the fibrinogen solution allows the thrombin to convert the fibrinogen to fibrin at the cell membrane's outer surface. The fibrinogen solution may comprise unmodified fibrinogen. In some embodiments, the coating molecule comprises fibrinogen conjugated to dibenzocyclooctyne (DBCO) (fibrinogen-DBCO). Fibrinogen is conjugated to dibenzocyclooctyne (DBCO) to enable bioorthogonal click chemistry, specifically strain-promoted alkyne–azide cycloaddition (SPAAC). SPAAC is a bioorthogonal click chemistry reaction that allows for fast, specific, and catalyst-free covalentAttorney Docket No.11196-120WO1 bonding between an azide group and a strained alkyne, most commonly dibenzocyclooctyne (DBCO). During SPAAC, an azide (-N^) reacts with a strained alkyne, typically DBCO, BCN, or BARAC. The result is the formation of a stable triazole ring without any catalyst. The reaction is driven by the ring strain in the alkyne, which makes it highly reactive even in physiological conditions. Herein, DBCO allows fibrinogen to react with azide-functionalized molecules (like polymers, peptides, surfaces, or other biomolecules) without interfering with biological systems. Further, no catalysts or toxic reagents are needed. The DBCO-azide reaction forms a stable triazole linkage, allowing fibrinogen to be precisely immobilized, crosslinked, or patterned. SPAAC reactions proceed at room / body temperature in an aqueous solution and are non-toxic, ideal for cell encapsulation, tissue engineering, or biosensing. In some embodiments, the coating molecule is provided to the microparticle, cell or therapeutic agent between about 1 mg / mL and about 20 mg / mL. In some embodiments, the coating molecule is provided to the microparticle, cell or therapeutic agent at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 mg / ml. In some embodiments, the coating molecule is about 10 mg / mL. A blending solution is a carefully prepared liquid mixture that contains one or more hydrogel-forming molecules (called blending molecules), designed to create a three-dimensional (3D) polymeric network, or hydrogel, when exposed to specific conditions such as changes in temperature, pH, enzymatic activity, or through chemical crosslinking. These solutions fabricate soft, hydrated, tissue-like materials that encapsulate cells, drugs, or biologics. The blending molecules may be negatively charged molecules or proteins. The blending molecules may form a hydrogel by themselves or with the polymer coating. Some exemplary blending molecules are gelatin, collagen, hyaluronic acid, alginate, fibrinogen, PEG (polyethylene glycol), PVA (polyvinyl alcohol), Pluronic F127, silk fibroin, elastin, recombinant peptides, genipin, glutaraldehyde, DBCO, azides, thiols, maleimide, tyrosine (for tyrosinase), lysine / glutamine (for transglutaminase), tyramine (for HRP), PNIPAM, methylcellulose, gelatin (at physiological temps). In some embodiments, the blending solution wherein the one or more blending molecules comprise an alginate. In some embodiments, the blending solution further comprises alginate- azide. In some embodiments, the blending solution comprises a mixture of sodium alginate solution (0.125% w / v) and alginate-azide solution (0.125% w / v). In some embodiments, the blending solution is between about 0.05% w / g and about 5% w / v. In some embodiments, the blending solution is about 0.25% w / v. In some embodiments, the coating molecule or the one or more blending molecules is conjugated to dibenzocyclooctyne (DBCO), while the other, the coating molecule or the one or more blending molecules, is conjugated to azide. In suchAttorney Docket No.11196-120WO1 embodiments, the DBCO will react with the azide groups on alginate-azide, crosslinking the fibrin and alginate at the cell membrane's outer surface. In exemplary embodiments, the alginate comprises sodium alginate. The alginate may comprise one or more of sodium alginate, potassium alginate, and ammonium alginate. In preferred embodiments, the alginate does not comprise calcium alginate. However, any suitable polymers, monomers, and macromers can be used. Alginates are refined from brown seaweeds. Alginates from different species have different physical properties, e.g., strong or weak gels, creams, etc. Sodium alginate is used in many foods, pharmaceuticals, etc., as a thickening agent, a gelling agent, a stabilizer, etc. In some embodiments, the blending solution is between about 0.05% w / g and about 5% w / v. In some embodiments, the blending solution is 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.20%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%, 0.27%, 0.28%, 0.29%, 0.30%, 0.31%, 0.32%, 0.3%3, 0.34%, 0.35%, 0.36%, 0.37%, 0.38%, 0.39%, 0.40%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%, 0.47%, 0.48%, 0.49%, 0.50%, 0.51%, 0.52%, 0.53%, 0.54%, 0.55%, 0.56%, 0.57%, 0.58%, 0.59%, 0.60%, 0.61%, 0.62%, 0.63%, 0.64%, 0.65%, 0.66%, 0.67%, 0.68%, 0.69%, 0.70%, 0.71%, 0.72%, 0.73%, 0.74%, 0.75%, 0.76%, 0.77%, 0.78%, 0.79%, 0.80%, 0.81%, 0.82%, 0.83%, 0.84%, 0.85%, 0.86%, 0.87%, 0.88%, 0.89%, 0.90%, 0.91%, 0.92%, 0.93%, 0.94%, 0.95%, 0.96%, 0.97%, 0.98%, 0.99%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, or 5.0% w / v. In some embodiments, the blending solution is about 0.25% w / v. In some embodiments, the blending solution comprises about 0.01% and about 2% w / v of blending molecules. In some embodiments, step (f), the blending solution comprises about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.2%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%, 0.27%, 0.28%, 0.29%, 0.3%, 0.31%, 0.32%, 0.3%3, 0.34%, 0.35%, 0.36%, 0.37%, 0.38%, 0.39%, 0.4%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%, 0.47%, 0.48%, 0.49%, 0.5%, 0.51%, 0.52%, 0.53%, 0.54%, 0.55%, 0.56%, 0.57%, 0.58%, 0.59%, 0.6%, 0.61%, 0.62%, 0.63%, 0.64%, 0.65%, 0.66%, 0.67%, 0.68%, 0.69%, 0.7%, 0.71%, 0.72%, 0.73%, 0.74%, 0.75%, 0.76%, 0.77%, 0.78%, 0.79%, 0.8%, 0.81%, 0.82%, 0.83%, 0.84%, 0.85%, 0.86%, 0.87%, 0.88%, 0.89%, 0.9%, 0.91%, 0.92%, 0.93%, 0.94%, 0.95%, 0.96%, 0.97%, 0.98%, 0.99%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2% w / v blending molecules. As disclosed herein, the polymer coating is further crosslinked with one or more blending molecules, by a fortifying solution, to form a hardened BZP. A fortifying solution is a secondaryAttorney Docket No.11196-120WO1 treatment applied after initial hydrogel formation or polymer coating to strengthen, stabilize, or functionalize the structure. It reacts chemically or physically with the preformed hydrogel and / or polymer coating to enhance mechanical integrity, biofunctionality, or chemical resistance. Some exemplary fortifying solutions are Genipin solution, Transglutaminase solution, Calcium chloride (CaCl^), EDC / NHS in MES buffer, Hydrogen peroxide + HRP, DOPA (dopamine) solution, PEG-dithiol (PEG-SH), Silane coupling solution, and Tannic acid solution. Genipin solution targets gelatin, fibrin, collagen, PEG-protein hybrids, transglutaminase solution targets fibrin, gelatin, casein hydrogels or coatings, Calcium chloride (CaCl^) targets alginate- based hydrogels or coatings, EDC / NHS in MES buffer targets carboxyl-containing hydrogels (e.g., hyaluronic acid) + amine-functional coatings, hydrogen peroxide + HRP targets tyramine- or phenol-functionalized hydrogels and coatings, DOPA (dopamine) solution targets PEG, PCL, or other inert polymer coatings, PEG-dithiol (PEG-SH) targets vinyl, maleimide, or acrylate-functionalized hydrogels or coatings, silane coupling solution targets silica, glass, or oxidized polymer surfaces, tannic acid solution targets gelatin, chitosan, polyphenol-compatible hydrogels. In some embodiments, the fortifying solution comprises polylysine and calcium chloride. In some embodiments, the fortifying solution comprises 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, or 0.10% w / v of polylysine. In some embodiments, the fortifying solution comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 mM calcium chloride solution. In some embodiments, the fortifying solution comprises 0.05% w / v of polylysine and 50 mM calcium chloride solution. The fortifying solution allows the BZP to form and harden on the cell surface. As described in the examples and exemplary embodiments, two or three crosslinking reactions occur. When the fibrinogen solution comprises fibrinogen-DBCO, and the alginate solution comprises alginate-azide, the fibrin is crosslinked with the alginate through click chemistry between the DBCO and azide groups. The alginate crosslinks through ionic interactions between the carboxylate groups and the Ca2+to form an alginate hydrogel. The alginate is further crosslinked with the polylysine through polyelectrolyte complexation, as these two molecules have opposite charges. As disclosed herein, the cell is selected from mesenchymal stem cell, human neural stem cell, pancreatic islet, articular chondrocyte, fibroblast, red blood cell, platelet, cancer cell, and microbial cell. In some embodiments, the microbial cell is a bacterium, fungus, or yeast. In some embodiments, the cell is a pancreatic islet cell. In some embodiments, the therapeutic agent is a drug or a biologically active compound. Examples include biotherapeutic anti-cancer agents and chemotherapeutic agents used in theAttorney Docket No.11196-120WO1 treatment of cancer. Exemplary biotherapeutic anti-cancer agents include, but are not limited to, interferons, cytokines (e.g., tumor necrosis factor, interferon ^, interferon ^), vaccines, hematopoietic growth factors, monoclonal serotherapy, immunostimulants and / or immunodulatory agents (e.g., IL-1, 2, 4, 6, or 12), immune cell growth factors (e.g., GM-CSF) and antibodies (e.g. HERCEPTIN (trastuzumab), T-DM1, AVASTIN (bevacizumab), ERBITUX (cetuximab), VECTIBIX (panitumumab), RITUXAN (rituximab), BEXXAR (tositumomab)). Exemplary chemotherapeutic agents include, but are not limited to, anti-estrogens (e.g. tamoxifen, raloxifene, and megestrol), LHRH agonists (e.g. goserelin and leuprolide), anti- androgens (e.g. flutamide and bicalutamide), photodynamic therapies (e.g. verteporfin (BPD- MA), phthalocyanine, photosensitizer Pc4, and demethoxy-hypocrellin A (2BA-2-DMHA)), nitrogen mustards (e.g. cyclophosphamide, ifosfamide, trofosfamide, chlorambucil, estramustine, and melphalan), nitrosoureas (e.g. carmustine (BCNU) and lomustine (CCNU)), alkylsulphonates (e.g. busulfan and treosulfan), triazenes (e.g. dacarbazine, temozolomide), platinum containing compounds (e.g. cisplatin, carboplatin, oxaliplatin), vinca alkaloids (e.g. vincristine, vinblastine, vindesine, and vinorelbine), taxoids (e.g. paclitaxel or a paclitaxel equivalent such as nanoparticle albumin-bound paclitaxel (ABRAXANE), docosahexaenoic acid bound-paclitaxel (DHA-paclitaxel, Taxoprexin), polyglutamate bound-paclitaxel (PG-paclitaxel, paclitaxel poliglumex, CT-2103, XYOTAX), the tumor-activated prodrug (TAP) ANG1005 (Angiopep-2 bound to three molecules of paclitaxel), paclitaxel-EC-1 (paclitaxel bound to the erbB2- recognizing peptide EC-1), and glucose-conjugated paclitaxel, e.g., 2^-paclitaxel methyl 2- glucopyranosyl succinate; docetaxel, taxol), epipodophyllins (e.g. etoposide, etoposide phosphate, teniposide, topotecan, 9-aminocamptothecin, camptoirinotecan, irinotecan, crisnatol, mytomycin C), anti-metabolites, DHFR inhibitors (e.g. methotrexate, dichloromethotrexate, trimetrexate, edatrexate), IMP dehydrogenase inhibitors (e.g. mycophenolic acid, tiazofurin, ribavirin, and EICAR), ribonucleotide reductase inhibitors (e.g. hydroxyurea and deferoxamine), uracil analogs (e.g. 5-fluorouracil (5-FU), floxuridine, doxifluridine, ratitrexed, tegafur-uracil, capecitabine), cytosine analogs (e.g. cytarabine (ara C), cytosine arabinoside, and fludarabine), purine analogs (e.g. mercaptopurine and Thioguanine), Vitamin D3 analogs (e.g. EB 1089, CB 1093, and KH 1060), isoprenylation inhibitors (e.g. lovastatin), dopaminergic neurotoxins (e.g.1- methyl-4-phenylpyridinium ion), cell cycle inhibitors (e.g. staurosporine), actinomycin (e.g. actinomycin D, dactinomycin), bleomycin (e.g. bleomycin A2, bleomycin B2, peplomycin), anthracycline (e.g. daunorubicin, doxorubicin, pegylated liposomal doxorubicin, idarubicin, epirubicin, pirarubicin, zorubicin, mitoxantrone), MDR inhibitors (e.g. verapamil), Ca2+ATPase inhibitors (e.g. thapsigargin), imatinib, thalidomide, lenalidomide, tyrosine kinase inhibitors (e.g.,Attorney Docket No.11196-120WO1 axitinib (AG013736), bosutinib (SKI-606), cediranib (RECENTIN™, AZD2171), dasatinib (SPRYCEL®, BMS-354825), erlotinib (TARCEVA®), gefitinib (IRESSA®), imatinib (Gleevec®, CGP57148B, STI-571), lapatinib (TYKERB®, TYVERB®), lestaurtinib (CEP-701), neratinib (HKI-272), nilotinib (TASIGNA®), semaxanib (semaxinib, SU5416), sunitinib (SUTENT®, SU11248), toceranib (PALLADIA®), vandetanib (ZACTIMA®, ZD6474), vatalanib (PTK787, PTK / ZK), trastuzumab (HERCEPTIN®), bevacizumab (AVASTIN®), rituximab (RITUXAN®), cetuximab (ERBITUX®), panitumumab (VECTIBIX®), ranibizumab (Lucentis®), nilotinib (TASIGNA®), sorafenib (NEXAVAR®), everolimus (AFINITOR®), alemtuzumab (CAMPATH®), gemtuzumab ozogamicin (MYLOTARG®), temsirolimus (TORISEL®), ENMD-2076, PCI-32765, AC220, dovitinib lactate (TKI258, CHIR-258), BIBW 2992 (TOVOK™), SGX523, PF-04217903, PF-02341066, PF-299804, BMS-777607, ABT-869, MP470, BIBF 1120 (VARGATEF®), AP24534, JNJ-26483327, MGCD265, DCC-2036, BMS- 690154, CEP-11981, tivozanib (AV-951), OSI-930, MM-121, XL-184, XL-647, and / or XL228), proteasome inhibitors (e.g., bortezomib (VELCADE)), mTOR inhibitors (e.g., rapamycin, temsirolimus (CCI-779), everolimus (RAD-001), ridaforolimus, AP23573 (Ariad), AZD8055 (AstraZeneca), BEZ235 (Novartis), BGT226 (Norvartis), XL765 (Sanofi Aventis), PF-4691502 (Pfizer), GDC0980 (Genetech), SF1126 (Semafoe) and OSI-027 (OSI)), oblimersen, gemcitabine, caminomycin, leucovorin, pemetrexed, cyclophosphamide, dacarbazine, procarbizine, prednisolone, dexamethasone, campathecin, plicamycin, asparaginase, aminopterin, methopterin, porfiromycin, melphalan, leurosidine, leurosine, chlorambucil, trabectedin, procarbazine, discodermolide, caminomycin, aminopterin, and hexamethyl melamine. In some embodiments, therapeutic agents comprise anti-inflammatory agents such as dexamethasone and ibuprofen. In some embodiments, the anti-inflammatory compound is a non- steroidal anti-inflammatory compound including, but is not limited to aspirin, ibuprofen, ketoprofen, naproxen, steroids, glucocorticoids (including, but not limited to betamethasone, budesonide, dexamethasone, hydrocortisone, hydrocortisone acetate, methylprednisolone, prednisolone, prednisone, and triamcinolone), methotrexate, sulfasalazine, leflunomide, anti- Tumor Necrosis Factor (TNF) medications, cyclophosphamide, and mycophenolate. In some embodiments, the anesthetic includes, but is not limited to, chloroprocaine, procaine, tetracaine, lidocaine, bupivacaine, ropivacaine, mepivacaine, and levobupivacaine. In some embodiments, the sedatives include, but are not limited to, barbiturates, benzodiazepines, nonbenzodiazepine hypnotics, antihistamines, muscle relaxants, opioids, and methaqualone, or derivatives thereof. In some embodiments, therapeutic agents comprise antibiotics like amoxicillin and ciprofloxacin to combat bacterial infections. The additional antibiotic composition comprises any one type of antibiotic including, but not limited to penicillins (including, but not limited toAttorney Docket No.11196-120WO1 amoxicillin, clavulanate and amoxicillin, ampicillin, dicloxacillin, oxacillin, and penicillin V potassium), tetracyclines (including, but not limited to demeclocycline, doxycycline, eravacycline, minocycline, omadacycline, sarecycline, and tetracycline), cephalosporins (cefaclor, cefadroxil, cefdinir, cephalexin, cefprozil, cefepime, cefiderocol, cefotaxime, cefotetan, ceftaroline, cefazidme, ceftriaxone, and cefuroxime), quinolones (also referred to as fluoroquinolones include, but are not limited to ciprofloxacin, delafloxacin, levofloxacin, moxifloxacin, and gemifloxacin), lincomycins (including clindamycin and lincomycin), macrolides (including, but not limited to azithromycin, clarithromycin, erythromycin, and fidaxomicin (ketolide)), sulfonamides (including sulfamethoxazole and trimethoprim, and sulfasalazine), glycopeptides (including, but not limited to dalbavancin, oritavancin, telavancin, and vancomycin), aminoglycosides (including, but not limited to gentamicin, tobramycin, and amikacin), carbapenems (including, but not limited to imipenem and cilastatin, meropenem, and ertapenem), and topical antibiotics (including, but not limited to neomycin, bacitracin, polymyxin B, and pyroxamine) used alone or in combination. Additional therapeutic agents comprise biologics, including monoclonal antibodies (e.g., trastuzumab for breast cancer or adalimumab for autoimmune disorders), representing a more targeted class of therapeutics. In gene therapy, therapeutic agents may include plasmid DNA, siRNA, or mRNA, as seen in mRNA vaccines. Additionally, hormonal therapies such as insulin for diabetes and estrogen for hormone replacement therapy are also key examples. Emerging treatments now incorporate nanoparticles or cell-based therapies, like engineered CAR-T cells used in hematological cancers, further expanding the landscape of therapeutic options. Method of coating a cell In one aspect, disclosed herein is a method for coating a cell with a biomimetic zona pellucida (BZP), the method comprising, (a) incubating the cell with an enzyme-binding molecule conjugated to a cell membrane insertion moiety, (b) incubating the cell with an enzyme that binds the enzyme-binding molecule, (c) incubating the cell with a coating solution comprising a coating molecule that binds the enzyme to form a polymer coating on the surface of the cell, (d) incubating the cell with a blending solution comprising one or more blending molecules that crosslink with the polymer coating to form a hydrogel layer on the surface of the cell, (e) incubating the cell with a fortifying solution that hardens the BZP when reacted with at least one of the hydrogel and the polymer coating, (f) incubating the cell with the blending solution, and (g) optionally repeating steps (d) through (e). Some examples of cells that can be coated with a biomimetic zona pellucida (BZP) include, but are not limited to, mesenchymal stem cells, human neural stem cells, pancreatic islet cells,Attorney Docket No.11196-120WO1 articular chondrocytes, fibroblasts, red blood cells, platelets, cancer cells, and microbial cells. In some embodiments, the microbial cell can be bacteria, fungi, or yeast. In some embodiments, the cell is a mammalian cell. In some embodiments, the cell is a primary cell. In exemplary embodiments, the cell is a pancreatic islet cell. In other exemplary embodiments, the cell is a mesenchymal stem cell (MSC), an MCF7 breast cancer cell, or an MDA-MB-231 breast cancer cell. As described herein, wherein the BZP comprises a 3D polymer meshwork bound to a functionalized surface of the cell. In some embodiments, the BZP is 10 to 30 µm in thickness. In some embodiments, the BZP is 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 µm in thickness. In some embodiments, the functionalized surface of the cell comprises an enzyme-binding molecule and an enzyme. Some examples of enzyme-binding molecules and the respective binding enzymes are Zona pellucida glycoproteins (substrate) which binds to enzyme, Arosin (in the acrosome) or Proacrosin, Hyaluronic acid which binds to enzyme hyaluronidase (e.g., PH-20) ZP proteins which bind to cathepsin-like proteases, extracellular matrix components that bind to Matrix Metalloproteinases (MMPs), plasminogen that binds to urokinase-type plasminogen activator (uPA), ubiquitinated proteins on the zona pellucida that can bind to sperm proteasome, ZP2 glycoprotein that binds to enzyme Ovastacin, L-tyrosine and L-DOPA (dihydroxyphenylalanine) which is a substrate for Tyrosinase, Glutamine residues in proteins (amine donor) and primary amines (amine acceptor, e.g., lysine) are a substrate for Transglutaminase, Hydrogen peroxide (H^O^) and electron donors (e.g., phenols, amines)are a substrate for Peroxidase, LPXTG motif- containing peptides and oligoglycine (nucleophile / acceptor)are substrates for Sortase (e.g., Sortase A), Hydrogen peroxide (H^O^) + chromogenic substrates (e.g., TMB, DAB, ABTS) are acted on by enzyme Horseradish Peroxidase (HRP), Phosphate monoesters (e.g., p-nitrophenyl phosphate — pNPP) are substrates for the enzyme, Alkaline Phosphatase (ALP), Starch is a substrate for Amylase, Peptides are substrates for Trypsin, DNA strand and nucleotides bind to DNA Polymerase, Acetylcholine is a substrate for Acetylcholinesterase, CO^ and H^O are substrates for Carbonic Anhydrase, Lactose is a substrate for Lactase, Glucose and ATP are substrates and co-substrates, respectively, for Hexokinase, specific peptide motifs are substrates for Caspase-3, Arachidonic acid is a substrate of Cyclooxygenase (COX-1 / COX-2), RNA template and nucleotides are substrates for Reverse Transcriptase. In some embodiments, the enzyme is selected from thrombin, tyrosinase, transglutaminase, peroxidase, sortase, horseradish peroxidase, and alkaline phosphatase. In some embodiments, the enzyme is a serine protease enzyme. In some embodiments, the serine protease enzyme is thrombin. In some embodiments, the enzyme-binding molecule is streptavidin. In some embodiments, the enzyme-bindingAttorney Docket No.11196-120WO1 molecule is an aptamer that binds the enzyme. In some embodiments, the enzyme-binding molecule is a biotinylated DNA aptamer. In some embodiments, the enzyme-binding molecules are other aptamers such as, for example, anti-thrombin aptamer. In some embodiments, the enzyme-binding molecule is an anti-thrombin aptamer comprising a sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3. In exemplary embodiments, the anti-thrombin aptamer is Apt-1 (SEQ ID NO: 1), Apt-2 (SEQ ID NO: 2), or Apt-3 (SEQ ID NO: 3). In preferred embodiments, the anti-thrombin aptamer is Apt-2 (SEQ ID NO: 2). In some embodiments, the anti-thrombin aptamer comprises SEQ ID NO: 2. In other exemplary embodiments, the enzyme-binding molecule is a complementary DNA (cDNA) molecule, and the enzyme is conjugated to a DNA molecule, wherein the cDNA molecule and DNA molecule hybridize with each other, thereby joining the enzyme and enzyme-binding molecule. In some embodiments, the enzyme is provided to the cell at between about 0.1 U / mL and about 10 U / mL and in some cases, the enzyme is provided to the cell at about 1 U / ml. In some embodiments, the enzyme is provided to the cell at about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, or 10 U / mL. In some embodiments, the enzyme is provided to the cell at about 1 U / ml. A cell membrane insertion moiety is a chemical group or molecular structure that facilitates the stable incorporation of a compound, peptide, or nanoparticle into the lipid bilayer of a cell membrane. These moieties take advantage of the amphipathic nature of cell membranes, typically anchoring via hydrophobic interactions with the lipid tails while presenting functional domains on the membrane surface. They are widely used in drug delivery, cell labeling, synthetic biology, and cell-surface engineering to display molecules or modify cell behavior without internalization. Some exemplary cell membrane insertion moieties are, but not limited to, cholesterol, a diacyl lipid, a tocopherol, a ceramide, a sphingomyelin, a phosphatidylcholine, a phosphatidylethanolamine, a phosphatidylserine, a glycolipid, and a fatty acid. In some cases, the cell membrane insertion moiety comprises cholesterol. Further disclosed herein, is that the 3D polymer meshwork comprises a polymer coating crosslinked with one or more blending molecules, comprised in a blending solution. In some embodiments, the polymer coating comprises a coating molecule. Coating molecules (also called crosslinkers, anchoring agents, or polymerizable substrates) can bind enzymes and help form a polymer or functional coating on a surface. Coating molecules are often used in biomaterials, biosensors, and surface functionalization.Attorney Docket No.11196-120WO1 Some exemplary coating molecules are DOPA / Dopamine, Fibrinogen, Gelatin / Casein / Collagen, Tyramine, Phenol- or aniline-derivatives, p-Aminophenylalanine-PEG, p-Nitrophenyl phosphate (pNPP), Acryloyl-PEG-NHS, Maleimide-functionalized PEG, and NHS-Activated Polymers. Tyrosinase oxidizes dopamine to form polydopamine, which is a universal adhesive coating. Fibrinogen is crosslinked by transglutaminase to form fibrin-like hydrogel networks. Gelatin / Casein / Collagen forms protein-based polymer films or scaffolds via crosslinking of glutamine and lysine residues in the presence of transglutaminase. HRP + H^O^ polymerize tyramine into adhesive hydrogels or surface coatings. Phenol- or aniline-derivatives are oxidatively polymerized into conductive or adhesive coatings (e.g., poly(phenol)) by peroxidase / laccase. p-Aminophenylalanine-PEG in the presence of Sortase A is covalently ligated to proteins with LPXTG motifs, which allows site-specific surface anchoring. Alkaline Phosphatase (ALP) cleaves p-Nitrophenyl phosphate (pNPP) to produce a colorimetric signal, which is sometimes used in signal amplification for bioactive coatings. Any enzyme with lysine residues reacts with amine groups on enzymes such as, for example, Acryloyl-PEG-NHS, to anchor them to polymerizing acrylate systems. Enzymes with thiol (-SH) groups use Maleimide- functionalized PEG as a substrate to form stable thioether linkages to covalently attach enzymes to surfaces or networks. NHS-Activated Polymers covalently bind any primary amine-containing enzyme to a polymer scaffold via amide bond formation. In some embodiments, the coating molecule comprises fibrinogen, and the polymer coating is fibrin. In some embodiments, the coating molecule comprises fibrinogen conjugated to dibenzocyclooctyne (DBCO) (fibrinogen-DBCO). Fibrinogen is conjugated to dibenzocyclooctyne (DBCO) to enable bioorthogonal click chemistry, specifically strain- promoted alkyne–azide cycloaddition (SPAAC). SPAAC is a bioorthogonal click chemistry reaction that allows for fast, specific, and catalyst-free covalent bonding between an azide group and a strained alkyne, most commonly dibenzocyclooctyne (DBCO). During SPAAC An azide (- N^) reacts with a strained alkyne, typically DBCO, BCN, or BARAC. The result is the formation of a stable triazole ring without needing any catalyst. The reaction is driven by the ring strain in the alkyne, which makes it highly reactive even in physiological conditions. Herein, DBCO allows fibrinogen to react with azide-functionalized molecules (like polymers, peptides, surfaces, or other biomolecules) without interfering with biological systems. Further, no catalysts or toxic reagents are needed. The DBCO-azide reaction forms a stable triazole linkage, allowing fibrinogen to be precisely immobilized, crosslinked, or patterned. SPAAC reactions proceed at room / body temperature in an aqueous solution and are non-toxic, ideal for cell encapsulation, tissue engineering, or biosensing. In some embodiments, the coating molecule is provided to the cell at between about 1Attorney Docket No.11196-120WO1 mg / mL and about 20 mg / mL. In some embodiments, the coating molecule is provided to the cell at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 mg / ml. In some embodiments, the coating molecule is provided to the cell about 10 mg / mL. A blending solution is a carefully prepared liquid mixture that contains one or more hydrogel-forming molecules (called blending molecules), designed to create a three-dimensional (3D) polymeric network, or hydrogel, when exposed to specific conditions such as changes in temperature, pH, enzymatic activity, or through chemical crosslinking. These solutions fabricate soft, hydrated, tissue-like materials that encapsulate cells, drugs, or biologics. The blending molecules may be negatively charged molecules or proteins. The blending molecules may form a hydrogel by themselves or with the polymer coating. Some exemplary blending molecules are gelatin, collagen, hyaluronic acid, alginate, fibrinogen, PEG (polyethylene glycol), PVA (polyvinyl alcohol), Pluronic F127, silk fibroin, elastin, recombinant peptides, genipin, glutaraldehyde, DBCO, azides, thiols, maleimide, tyrosine (for tyrosinase), lysine / glutamine (for transglutaminase), tyramine (for HRP), PNIPAM, methylcellulose, gelatin (at physiological temps). In some embodiments, the blending solution wherein the one or more blending molecules comprise an alginate. In some embodiments, the blending solution further comprises alginate- azide. In some embodiments, the blending solution comprises a mixture of sodium alginate solution (0.125% w / v) and alginate-azide solution (0.125% w / v). In some embodiments, the coating molecule or the one or more blending molecule is conjugated to dibenzocyclooctyne (DBCO), and while the other, the coating molecule or the one or more blending molecule, is conjugated to azide. In such embodiments, the DBCO will react with the azide groups on alginate- azide, crosslinking the fibrin and alginate at the outer surface of the cell membrane. In exemplary embodiments, the alginate comprises sodium alginate. The alginate may comprise one or more of sodium alginate, potassium alginate, and ammonium alginate. In preferred embodiments, the alginate does not comprise calcium alginate. However, any suitable polymers, monomers, and macromers can be used. Alginates are refined from brown seaweeds. Alginates from different species have different physical properties, e.g. strong or weak gels, creams, etc. Sodium alginate is used in many foods, pharmaceuticals, etc., as a thickening agent, a gelling agent, a stabilizer, etc. In some embodiments, the blending solution is between about 0.05% w / g and about 5% w / v. In some embodiments, the blending solution is 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.20%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%, 0.27%, 0.28%, 0.29%, 0.30%, 0.31%, 0.32%, 0.3%3, 0.34%, 0.35%, 0.36%, 0.37%, 0.38%, 0.39%, 0.40%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%,Attorney Docket No.11196-120WO1 0.46%, 0.47%, 0.48%, 0.49%, 0.50%, 0.51%, 0.52%, 0.53%, 0.54%, 0.55%, 0.56%, 0.57%, 0.58%, 0.59%, 0.60%, 0.61%, 0.62%, 0.63%, 0.64%, 0.65%, 0.66%, 0.67%, 0.68%, 0.69%, 0.70%, 0.71%, 0.72%, 0.73%, 0.74%, 0.75%, 0.76%, 0.77%, 0.78%, 0.79%, 0.80%, 0.81%, 0.82%, 0.83%, 0.84%, 0.85%, 0.86%, 0.87%, 0.88%, 0.89%, 0.90%, 0.91%, 0.92%, 0.93%, 0.94%, 0.95%, 0.96%, 0.97%, 0.98%, 0.99%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, or 5.0% w / v. In some embodiments, the blending solution is about 0.25% w / v. In some embodiments, the blending solution comprises about 0.01% and about 2% w / v blending molecules. In some embodiments, step (f), the blending solution comprises about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.2%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%, 0.27%, 0.28%, 0.29%, 0.3%, 0.31%, 0.32%, 0.3%3, 0.34%, 0.35%, 0.36%, 0.37%, 0.38%, 0.39%, 0.4%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%, 0.47%, 0.48%, 0.49%, 0.5%, 0.51%, 0.52%, 0.53%, 0.54%, 0.55%, 0.56%, 0.57%, 0.58%, 0.59%, 0.6%, 0.61%, 0.62%, 0.63%, 0.64%, 0.65%, 0.66%, 0.67%, 0.68%, 0.69%, 0.7%, 0.71%, 0.72%, 0.73%, 0.74%, 0.75%, 0.76%, 0.77%, 0.78%, 0.79%, 0.8%, 0.81%, 0.82%, 0.83%, 0.84%, 0.85%, 0.86%, 0.87%, 0.88%, 0.89%, 0.9%, 0.91%, 0.92%, 0.93%, 0.94%, 0.95%, 0.96%, 0.97%, 0.98%, 0.99%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2% w / v blending molecules. In some embodiments, the polymer coating is further crosslinked with one or more blending molecules, by a fortifying solution, to form a hardened BZP. A fortifying solution is a secondary treatment applied after initial hydrogel formation or polymer coating to strengthen, stabilize, or functionalize the structure. It reacts chemically or physically with the preformed hydrogel and / or polymer coating to enhance mechanical integrity, biofunctionality, or chemical resistance. Some exemplary fortifying solutions are Genipin solution, Transglutaminase solution, Calcium chloride (CaCl^), EDC / NHS in MES buffer, Hydrogen peroxide + HRP, DOPA (dopamine) solution, PEG-dithiol (PEG-SH), Silane coupling solution, Tannic acid solution. Genipin solution targets gelatin, fibrin, collagen, PEG-protein hybrids, transglutaminase solution targets fibrin, gelatin, casein hydrogels or coatings, Calcium chloride (CaCl^) targets alginate- based hydrogels or coatings, EDC / NHS in MES buffer targets carboxyl-containing hydrogels (e.g., hyaluronic acid) + amine-functional coatings, hydrogen peroxide + HRP targets tyramine- or phenol-functionalized hydrogels and coatings, DOPA (dopamine) solution targets PEG, PCL, or other inert polymer coatings, PEG-dithiol (PEG-SH) targets vinyl, maleimide, orAttorney Docket No.11196-120WO1 acrylate-functionalized hydrogels or coatings, silane coupling solution targets silica, glass, or oxidized polymer surfaces, tannic acid solution targets gelatin, chitosan, polyphenol-compatible hydrogels. In some embodiments, the fortifying solution comprises polylysine and calcium chloride. In some embodiments, the fortifying solution comprises 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, or 0.10% w / v of polylysine. In some embodiments, the fortifying solution comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 mM calcium chloride solution. In some embodiments, the fortifying solution comprises 0.05% w / v of polylysine and 50mM calcium chloride solution. The fortifying solution allows the BZP to form and harden on the cell surface. As described in the examples and exemplary embodiments, two or three crosslinking reactions occur. When the fibrinogen solution comprises fibrinogen-DBCO, and when the alginate solution comprises alginate-azide, the fibrin is crosslinked with the alginate through click chemistry between the DBCO and azide groups. The alginate crosslinks through ionic interactions between the carboxylate groups and the Ca2+to form an alginate hydrogel. The alginate is further crosslinked with the polylysine through polyelectrolyte complexation, as these two molecules have opposite charges. In some embodiments, step (a) is performed at between about 0°C and about 37°C. In some embodiments, step (a) is performed at 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, or 37°C. In some embodiments, step (a) is performed at room temperature. In some embodiments, step (a) is performed for between about 1 minute and about 60 minutes. In some embodiments, step (a) is performed for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 minutes. In some embodiments, step (a) is performed for about 15 minutes. In some embodiments, step (a), the cell is incubated on with gentle agitation. Gentle agitation may be done on a rotator, a rocker, an oscillator, or any other device that mixes the solution with low force. The agitation may be done at a speed of between about 30 rpm to about 300 rpm, or any speed or range in between. In some embodiments, step (b) is performed for between about 1 and about 30 min. In some embodiments, step (b) is performed for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 minutes. In some embodiments, step (b) is performed for about 15 min. In some embodiments, step (b) is performed at between about 0°C and about 37°C. In some embodiments, step (b) is performed at 1°C, 2°C, 3°C, 4°C, 5°C, 6°C,Attorney Docket No.11196-120WO1 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, or 37°C. In some embodiments, step (b) is performed at about room temperature. In some embodiments, step (c) is performed for between about 1 and about 60 minutes. In some embodiments, step (c) is performed for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 minutes. In some embodiments, step (c) is performed for about 10 min. In some embodiments, step (c) is performed at between about 0°C and about 37°C. In some embodiments, step (c) is performed at 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, or 37°C. In some embodiments, step (c) is performed at about 37°C. In some embodiments, step (d) is performed at between about 0°C and about 37°C. In some embodiments, step (d) is performed at 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, or 37°C. In some embodiments, step (d) is performed at room temperature. In some embodiments, step (d) is performed for between about 2 minutes and about 2 hours. In some embodiments, step (d) is performed for about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119 minutes or about 2 hours. In some embodiments, step (d) is performed for about 60 min. In some embodiments, step (d), the cell is incubated with gentle agitation. In some embodiments, step (e) is performed for between about 1 minute and about 20 minutes. In some embodiments, step (e) is performed for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 minutes. In some embodiments, step (e) is performed for about 5 minutes. In some embodiments, step (f) is performed for between about 1 minute and about 30 minutes. In some embodiments, step (f) is performed for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 minutes. In some embodiments, step (f) is performed for about 5 minutes. In some embodiments, the method is performed at between about 0°C and about 37°C. In some embodiments, the method is performed at about 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C,Attorney Docket No.11196-120WO1 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, or 37°C. In some cases, the method is performed at room temperature. The method may include various wash steps, wherein the cell is washed in serum free cell culture medium or a physiological buffer such as DPBS. In some embodiments, the method further comprising at least one of, washing the pancreatic islet cell before step (a); washing the pancreatic islet cell between steps (a) and (b); washing the pancreatic islet cell between steps (b) and (c); washing the pancreatic islet cell between steps (c) and (d); washing the pancreatic islet cell between steps (e) and (f); and washing the pancreatic islet cell after step (f). Each wash step comprises at least one wash. Each wash step may comprise between one and three washes. In exemplary embodiments, the cell is washed twice before step (a). In exemplary embodiments, the cell is washed twice between steps (a) and (b). The cell may be washed by gentle agitation or gentle pipetting. In embodiments, the method may further comprise step (g) repeating steps (d) through (e). The steps may be repeated until the BZP is formed. Method of treatment In one aspect, disclosed herein is a method of treating diabetes in a subject, comprising administering to the subject a pancreatic islet cell coated with a biomimetic zona pellucida (BZP). The cell may be a mammalian cell. The cell may be a pancreatic islet cell. An “islet cell” is an endocrine cell derived from a mammalian pancreas. Islet cells include alpha cells that secrete glucagon, beta cells that secrete insulin and amylin, delta cells that secrete somatostatin, PP cells that secrete pancreatic polypeptide, or epsilon cells that secrete ghrelin. The term includes homogenous and heterogenous populations of these cells. In preferred embodiments, a population of islet cells contains at least beta cells. In some aspects, a pancreatic islet cell coated with a biomimetic zona pellucida (BZP), wherein the BZP comprises a 3-dimensional (3D) polymer meshwork bound to the microparticle's functionalized surface, wherein the functionalized surface of the microparticle comprises an enzyme- binding molecule and an enzyme. In some aspects, the pancreatic islet cell coated with BZP exhibits a reduced degree of susceptibility to proinflammatory cytokines. In some aspects, the pancreatic islet cell coated with BZP decreased blood glucose levels in a treated subject compared to a control. In some aspects, the decreased blood glucose levels indicate an effective treatment of diabetes. In some aspects, the control comprises an untreated subject. In some aspects, the control comprises administering to the subject a naked pancreatic islet cell. In some aspects, the control comprises a sample from the subject at an earlier time period. Some examples of enzyme-binding molecules and the respective binding enzymes areAttorney Docket No.11196-120WO1 Zona pellucida glycoproteins (substrate) which binds to enzyme, Arosin (in the acrosome) or Proacrosin, Hyaluronic acid which binds to enzyme hyaluronidase (e.g., PH-20) ZP proteins which bind to cathepsin-like proteases, extracellular matrix components that bind to Matrix Metalloproteinases (MMPs), plasminogen that binds to urokinase-type plasminogen activator (uPA), ubiquitinated proteins on the zona pellucida that can bind to sperm proteasome, ZP2 glycoprotein that binds to enzyme Ovastacin, L-tyrosine and L-DOPA (dihydroxyphenylalanine) which is a substrate for Tyrosinase, Glutamine residues in proteins (amine donor) and primary amines (amine acceptor, e.g., lysine) are a substrate for Transglutaminase, Hydrogen peroxide (H^O^) and electron donors (e.g., phenols, amines)are a substrate for Peroxidase, LPXTG motif- containing peptides and oligoglycine (nucleophile / acceptor)are substrates for Sortase (e.g., Sortase A), Hydrogen peroxide (H^O^) + chromogenic substrates (e.g., TMB, DAB, ABTS) are acted on by enzyme Horseradish Peroxidase (HRP), Phosphate monoesters (e.g., p-nitrophenyl phosphate — pNPP) are substrates for the enzyme, Alkaline Phosphatase (ALP), Starch is a substrate for Amylase, Peptides are substrates for Trypsin, DNA strand and nucleotides bind to DNA Polymerase, Acetylcholine is a substrate for Acetylcholinesterase, CO^ and H^O are substrates for Carbonic Anhydrase, Lactose is a substrate for Lactase, Glucose and ATP are substrates and co-substrates, respectively, for Hexokinase, specific peptide motifs are substrates for Caspase-3, Arachidonic acid is a substrate of Cyclooxygenase (COX-1 / COX-2), RNA template and nucleotides are substrates for Reverse Transcriptase. In some embodiments, the enzyme-binding molecule is streptavidin. In some embodiments, the enzyme-binding molecule is an aptamer that binds the enzyme. In some embodiments, the enzyme-binding molecule is a biotinylated DNA aptamer. In some embodiments, the enzyme-binding molecules are other aptamers, such as, for example, an anti-thrombin aptamer. In some embodiments, the enzyme- binding molecule is an anti-thrombin aptamer comprising a sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3. In exemplary embodiments, the anti-thrombin aptamer is Apt-1 (SEQ ID NO: 1), Apt-2 (SEQ ID NO: 2), or Apt-3 (SEQ ID NO: 3). In preferred embodiments, the anti-thrombin aptamer is Apt-2 (SEQ ID NO: 2). In some embodiments, the anti-thrombin aptamer comprises SEQ ID NO: 2. In other exemplary embodiments, the enzyme- binding molecule is a complementary DNA (cDNA) molecule, and the enzyme is conjugated to a DNA molecule, wherein the cDNA molecule and DNA molecule hybridize with each other, thereby joining the enzyme and enzyme-binding molecule. In some embodiments, the enzyme is selected from thrombin, tyrosinase, transglutaminase, peroxidase, sortase, horseradish peroxidase, and alkaline phosphatase. In some embodiments, the enzyme is a serine protease enzyme. In some embodiments, the serine protease enzyme is thrombin. In some embodiments, the enzyme is provided to the pancreatic islet cell at between aboutAttorney Docket No.11196-120WO1 0.1 U / mL and about 10 U / mL; in some cases, the enzyme is provided to the pancreatic islet cell at about 1 U / ml. In some embodiments, the enzyme is provided to the pancreatic islet cell at about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, or 10 U / mL. In some embodiments, the enzyme is provided to the pancreatic islet cell at about 1 U / ml. As described herein, wherein the BZP comprises a 3D polymer meshwork bound to a functionalized surface of the cell. In some embodiments, the BZP is 10 to 30 µm in thickness. In some embodiments, the BZP is 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 µm in thickness. In some embodiments, the functionalized surface of the cell comprises an enzyme-binding molecule and an enzyme. A cell membrane insertion moiety is a chemical group or molecular structure that facilitates the stable incorporation of a compound, peptide, or nanoparticle into the lipid bilayer of a cell membrane. These moieties take advantage of the amphipathic nature of cell membranes, typically anchoring via hydrophobic interactions with the lipid tails while presenting functional domains on the membrane surface. They are widely used in drug delivery, cell labeling, synthetic biology, and cell-surface engineering to display molecules or modify cell behavior without internalization. Some exemplary cell membrane insertion moieties are, but not limited to, cholesterol, a diacyl lipid, a tocopherol, a ceramide, a sphingomyelin, a phosphatidylcholine, a phosphatidylethanolamine, a phosphatidylserine, a glycolipid, and a fatty acid. In some cases, the cell membrane insertion moiety comprises cholesterol. The cell membrane insertion moiety may be joined to the enzyme-binding molecule via a linker such as triethyleneglycol (TEG) or 10 thymine (10T). In exemplary embodiments, the anti-thrombin aptamer comprises 3’ Cholesterol with a TEG spacer (3CholTEG). Further disclosed herein, is that the 3D polymer meshwork comprises a polymer coating crosslinked with one or more blending molecules, comprised in a blending solution. In some embodiments, the polymer coating comprises a coating molecule. Coating molecules (also called crosslinkers, anchoring agents, or polymerizable substrates) can bind enzymes and help form a polymer or functional coating on a surface. Coating molecules are often used in biomaterials, biosensors, and surface functionalization. Some exemplary coating molecules are DOPA / Dopamine, Fibrinogen, Gelatin / Casein / Collagen, Tyramine, Phenol- or aniline-derivatives, p-Aminophenylalanine-PEG, p-Nitrophenyl phosphate (pNPP), Acryloyl-PEG-NHS, Maleimide-functionalized PEG, and NHS-Activated Polymers.Attorney Docket No.11196-120WO1 Tyrosinase oxidizes dopamine to form polydopamine, which is a universal adhesive coating. Fibrinogen is crosslinked by transglutaminase to form fibrin-like hydrogel networks. Gelatin / Casein / Collagen forms protein-based polymer films or scaffolds via crosslinking of glutamine and lysine residues in the presence of transglutaminase. HRP + H^O^ polymerize tyramine into adhesive hydrogels or surface coatings. Phenol- or aniline-derivatives are oxidatively polymerized into conductive or adhesive coatings (e.g., poly(phenol)) by peroxidase / laccase. p-Aminophenylalanine-PEG in the presence of Sortase A is covalently ligated to proteins with LPXTG motifs, which allows site-specific surface anchoring. Alkaline Phosphatase (ALP) cleaves p-Nitrophenyl phosphate (pNPP) to produce a colorimetric signal, which is sometimes used in signal amplification for bioactive coatings. Any enzyme with lysine residues reacts with amine groups on enzymes such as, for example, Acryloyl-PEG-NHS, to anchor them to polymerizing acrylate systems. Enzymes with thiol (-SH) groups use Maleimide- functionalized PEG as a substrate to form stable thioether linkages to covalently attach enzymes to surfaces or networks. NHS-Activated Polymers covalently bind any primary amine-containing enzyme to a polymer scaffold via amide bond formation. In some embodiments, the coating molecule comprises fibrinogen, and the polymer coating is fibrin. Fibrinogen is a plasma glycoprotein converted enzymatically by thrombin to fibrin and then forms a fibrin-based blood clot. Incubating the cell in the fibrinogen solution allows the thrombin to convert the fibrinogen to fibrin at the cell membrane's outer surface. The fibrinogen solution may comprise unmodified fibrinogen. In some embodiments, the coating molecule comprises fibrinogen conjugated to dibenzocyclooctyne (DBCO) (fibrinogen-DBCO). Fibrinogen is conjugated to dibenzocyclooctyne (DBCO) to enable bioorthogonal click chemistry, specifically strain-promoted alkyne–azide cycloaddition (SPAAC). SPAAC is a bioorthogonal click chemistry reaction that allows for fast, specific, and catalyst-free covalent bonding between an azide group and a strained alkyne, most commonly dibenzocyclooctyne (DBCO). During SPAAC An azide (-N^) reacts with a strained alkyne, typically DBCO, BCN, or BARAC. The result is the formation of a stable triazole ring without needing any catalyst. The reaction is driven by the ring strain in the alkyne, which makes it highly reactive even in physiological conditions. Herein, DBCO allows fibrinogen to react with azide-functionalized molecules (like polymers, peptides, surfaces, or other biomolecules) without interfering with biological systems. Further, no catalysts or toxic reagents are needed. The DBCO-azide reaction forms a stable triazole linkage, allowing fibrinogen to be precisely immobilized, crosslinked, or patterned. SPAAC reactions proceed at room / body temperature in an aqueous solution and are non-toxic, ideal for cell encapsulation, tissue engineering, or biosensing. In some embodiments, the coating molecule is provided to the pancreatic islet cell atAttorney Docket No.11196-120WO1 between about 1 mg / mL and about 20 mg / mL. In some embodiments, the coating molecule is provided to the pancreatic islet cell at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 mg / ml. In some embodiments, the coating molecule is provided to the pancreatic islet cell about 10 mg / mL. A blending solution is a carefully prepared liquid mixture that contains one or more hydrogel-forming molecules (called blending molecules), designed to create a three-dimensional (3D) polymeric network, or hydrogel, when exposed to specific conditions such as changes in temperature, pH, enzymatic activity, or through chemical crosslinking. These solutions fabricate soft, hydrated, tissue-like materials that encapsulate cells, drugs, or biologics. The blending molecules may be negatively charged molecules or proteins. The blending molecules may form a hydrogel by themselves or with the polymer coating. Some exemplary blending molecules are gelatin, collagen, hyaluronic acid, alginate, fibrinogen, PEG (polyethylene glycol), PVA (polyvinyl alcohol), Pluronic F127, silk fibroin, elastin, recombinant peptides, genipin, glutaraldehyde, DBCO, azides, thiols, maleimide, tyrosine (for tyrosinase), lysine / glutamine (for transglutaminase), tyramine (for HRP), PNIPAM, methylcellulose, gelatin (at physiological temps). In some embodiments, the blending solution wherein the one or more blending molecules comprise an alginate. In some embodiments, the blending solution further comprises alginate- azide. In some embodiments, the blending solution comprises a mixture of sodium alginate solution (0.125% w / v) and alginate-azide solution (0.125% w / v). In some embodiments, the coating molecule or the one or more blending molecule is conjugated to dibenzocyclooctyne (DBCO), and while the other, the coating molecule or the one or more blending molecule, is conjugated to azide. In such embodiments, the DBCO will react with the azide groups on alginate- azide, crosslinking the fibrin and alginate at the outer surface of the cell membrane. In exemplary embodiments, the alginate comprises sodium alginate. The alginate may comprise one or more of sodium alginate, potassium alginate, and ammonium alginate. In preferred embodiments, the alginate does not comprise calcium alginate. However, any suitable polymers, monomers, and macromers can be used. Alginates are refined from brown seaweeds. Alginates from different species have different physical properties, e.g. strong or weak gels, creams, etc. Sodium alginate is used in many foods, pharmaceuticals, etc., as a thickening agent, a gelling agent, a stabilizer, etc. In some embodiments, the blending solution is between about 0.05% w / g and about 5% w / v. In some embodiments, the blending solution is 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.20%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%, 0.27%, 0.28%, 0.29%, 0.30%, 0.31%, 0.32%, 0.3%3,Attorney Docket No.11196-120WO1 0.34%, 0.35%, 0.36%, 0.37%, 0.38%, 0.39%, 0.40%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%, 0.47%, 0.48%, 0.49%, 0.50%, 0.51%, 0.52%, 0.53%, 0.54%, 0.55%, 0.56%, 0.57%, 0.58%, 0.59%, 0.60%, 0.61%, 0.62%, 0.63%, 0.64%, 0.65%, 0.66%, 0.67%, 0.68%, 0.69%, 0.70%, 0.71%, 0.72%, 0.73%, 0.74%, 0.75%, 0.76%, 0.77%, 0.78%, 0.79%, 0.80%, 0.81%, 0.82%, 0.83%, 0.84%, 0.85%, 0.86%, 0.87%, 0.88%, 0.89%, 0.90%, 0.91%, 0.92%, 0.93%, 0.94%, 0.95%, 0.96%, 0.97%, 0.98%, 0.99%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, or 5.0% w / v. In some embodiments, the blending solution is about 0.25% w / v. In some embodiments, the blending solution comprises about 0.01% and about 2% w / v blending molecules. In some embodiments, step (f), the blending solution comprises about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.2%, 0.21%, 0.22%, 0.23%, 0.24%, 0.25%, 0.26%, 0.27%, 0.28%, 0.29%, 0.3%, 0.31%, 0.32%, 0.3%3, 0.34%, 0.35%, 0.36%, 0.37%, 0.38%, 0.39%, 0.4%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%, 0.47%, 0.48%, 0.49%, 0.5%, 0.51%, 0.52%, 0.53%, 0.54%, 0.55%, 0.56%, 0.57%, 0.58%, 0.59%, 0.6%, 0.61%, 0.62%, 0.63%, 0.64%, 0.65%, 0.66%, 0.67%, 0.68%, 0.69%, 0.7%, 0.71%, 0.72%, 0.73%, 0.74%, 0.75%, 0.76%, 0.77%, 0.78%, 0.79%, 0.8%, 0.81%, 0.82%, 0.83%, 0.84%, 0.85%, 0.86%, 0.87%, 0.88%, 0.89%, 0.9%, 0.91%, 0.92%, 0.93%, 0.94%, 0.95%, 0.96%, 0.97%, 0.98%, 0.99%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2% w / v blending molecules. In some embodiments, the polymer coating is further crosslinked with one or more blending molecules, by a fortifying solution, to form a hardened BZP. A fortifying solution is a secondary treatment applied after initial hydrogel formation or polymer coating to strengthen, stabilize, or functionalize the structure. It reacts chemically or physically with the preformed hydrogel and / or polymer coating to enhance mechanical integrity, biofunctionality, or chemical resistance. Some exemplary fortifying solutions are Genipin solution, Transglutaminase solution, Calcium chloride (CaCl^), EDC / NHS in MES buffer, Hydrogen peroxide + HRP, DOPA (dopamine) solution, PEG-dithiol (PEG-SH), Silane coupling solution, Tannic acid solution. Genipin solution targets gelatin, fibrin, collagen, PEG-protein hybrids, transglutaminase solution targets fibrin, gelatin, casein hydrogels or coatings, Calcium chloride (CaCl^) targets alginate- based hydrogels or coatings, EDC / NHS in MES buffer targets carboxyl-containing hydrogels (e.g., hyaluronic acid) + amine-functional coatings, hydrogen peroxide + HRP targets tyramine- or phenol-functionalized hydrogels and coatings, DOPA (dopamine) solution targets PEG,Attorney Docket No.11196-120WO1 PCL, or other inert polymer coatings, PEG-dithiol (PEG-SH) targets vinyl, maleimide, or acrylate-functionalized hydrogels or coatings, silane coupling solution targets silica, glass, or oxidized polymer surfaces, tannic acid solution targets gelatin, chitosan, polyphenol-compatible hydrogels. In some embodiments, the fortifying solution comprises polylysine and calcium chloride. In some embodiments, the fortifying solution comprises 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, or 0.10% w / v of polylysine. In some embodiments, the fortifying solution comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 mM calcium chloride solution. In some embodiments, the fortifying solution comprises 0.05% w / v of polylysine and 50mM calcium chloride solution. The fortifying solution allows the BZP to form and harden on the cell surface. As described in the examples and exemplary embodiments, two or three crosslinking reactions occur. When the fibrinogen solution comprises fibrinogen-DBCO, and when the alginate solution comprises alginate-azide, the fibrin is crosslinked with the alginate through click chemistry between the DBCO and azide groups. The alginate crosslinks through ionic interactions between the carboxylate groups and the Ca2+to form an alginate hydrogel. The alginate is further crosslinked with the polylysine through polyelectrolyte complexation, as these two molecules have opposite charges. Further disclosed herein is a method for reducing a blood glucose level in a subject in need thereof, the method comprising administering to the subject the pancreatic islet cell coated with a biomimetic zona pellucida (BZP), prepared by any of the methods disclosed herein. The pancreatic islet cell coated with a biomimetic zona pellucida (BZP) may be administered in such amounts, time, and route deemed necessary in order to achieve the desired result. The exact amount of the pancreatic islet cells coated with a biomimetic zona pellucida (BZP) will vary from subject to subject, depending on the species, age, and general condition of the subject, the severity of the diabetes, the particular pancreatic islet cell coated with a biomimetic zona pellucida (BZP), its mode of administration, its mode of activity, and the like. The pancreatic islet cell coated with a biomimetic zona pellucida (BZP) is preferably formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the pancreatic islet cell coated with a biomimetic zona pellucida (BZP) will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject will depend upon a variety of factors including the diabetes being treated and the severity of the diabetes; the activity of the pancreatic islet cell coated with a biomimetic zona pellucida (BZP) employed; the specific pancreatic islet cell coated with a biomimetic zona pellucida (BZP) employed; the age,Attorney Docket No.11196-120WO1 body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific pancreatic islet cell coated with a biomimetic zona pellucida (BZP) employed; the duration of the treatment; drugs used in combination or coincidental with the specific pancreatic islet cell coated with a biomimetic zona pellucida (BZP) employed; and like factors well known in the medical arts. The pancreatic islet cell coated with a biomimetic zona pellucida (BZP) may be administered by any route. In some embodiments, the pancreatic islet cell coated with a biomimetic zona pellucida (BZP) is administered via a variety of routes, including oral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, interdermal, rectal, intravaginal, intraperitoneal, topical (as by powders, ointments, creams, and / or drops), mucosal, nasal, buccal, enteral, sublingual; by intratracheal instillation, bronchial instillation, and / or inhalation; and / or as an oral spray, nasal spray, and / or aerosol. In general, the most appropriate route of administration will depend upon a variety of factors including the nature of the pancreatic islet cells coated with a biomimetic zona pellucida (BZP) (e.g., its stability in the environment of the gastrointestinal tract), the condition of the subject (e.g., whether the subject is able to tolerate oral administration), etc. The exact amount of pancreatic islet cells coated with a biomimetic zona pellucida (BZP) required to achieve a therapeutically or prophylactically effective amount will vary from subject to subject, depending on species, age, and general condition of a subject, severity of the side effects, identity of the particular compound(s), mode of administration, and the like. The amount to be administered to, for example, a child or an adolescent can be determined by a medical practitioner or person skilled in the art and can be lower or the same as that administered to an adult. The concentration of active agent(s) can vary widely and will be selected primarily based on activity of the active ingredient(s), body weight and the like in accordance with the particular mode of administration selected and the patient's needs. Concentrations, however, will typically be selected to provide dosages ranging from about 0.1 or 1 mg / kg / day to about 50 mg / kg / day and sometimes higher. Typical dosages range from about 3 mg / kg / day to about 3.5 mg / kg / day, preferably from about 3.5 mg / kg / day to about 7.2 mg / kg / day, more preferably from about 7.2 mg / kg / day to about 11.0 mg / kg / day, and most preferably from about 11.0 mg / kg / day to about 15.0 mg / kg / day. In certain preferred embodiments, dosages range from about 10 mg / kg / day to about 50 mg / kg / day. In certain embodiments, dosages range from about 20 mg to about 50 mg given orally twice daily. It will be appreciated that such dosages may be varied to optimize a therapeutic and / or prophylactic regimen in a particular subject or group of subjects. In one aspect, disclosed herein is a pancreatic islet cell coated with a biomimetic zonaAttorney Docket No.11196-120WO1 pellucida (BZP) of any preceding aspect and a pharmaceutically acceptable carrier selected from an excipient, a diluent, a salt, a buffer, a stabilizer, a lipid, an emulsion, a nanoparticle, and a cream. One or more active agents (e.g. pancreatic islet cells coated with a biomimetic zona pellucida (BZP)) can be administered in the “native” form or, if desired in the form of salts, esters, amides, prodrugs, or a derivative that is pharmacologically suitable. Salts, esters, amides, prodrugs, and other derivatives of the active agents can be prepared using standards procedures known to those skilled in the art of synthetic organic chemistry and described, for example, by March (1992) Advanced Organic Chemistry; Reactions, Mechanisms, and Structure, 4thEd. N.Y. Wiley-Interscience. In some embodiments, the pancreatic islet cells coated with a biomimetic zona pellucida (BZP) can be prepared as a “concentrate”, e.g. in a storage container of a premeasure volume and / or a predetermined amount ready for dilution, or in a soluble capsule ready for addition to a specified volume of water, saline, alcohol, hydrogen peroxide, or other diluent. In some embodiments, the pancreatic islet cells coated with a biomimetic zona pellucida (BZP) is administered 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, or more times. In some embodiments, the pancreatic islet cell coated with a biomimetic zona pellucida (BZP) is administered daily. In some embodiments, the pancreatic islet cells coated with a biomimetic zona pellucida (BZP) is administered every day, every 2 days, every 3 days, every 4 days, every 5 days, every 6 days, every 7 days, or more. In some embodiments, the pancreatic islet cells coated with a biomimetic zona pellucida (BZP) is administered every week, every 2 weeks, every 3 weeks, every 4 weeks, or more. In some embodiments, the pancreatic islet cells coated with a biomimetic zona pellucida (BZP) is administered every month, every 2 months, every 3 months, every 4 months, every 5 months, every 6 months, every 7 months, every 8 months, every 9 months, every 10 months, every 11 months, every 12 months, or more. In some embodiments, the pancreatic islet cells coated with a biomimetic zona pellucida (BZP) is administered every year, every 2 years, every 3 years, every 4 years, every 5 years, or more. EXAMPLES Example 1: Biomimetic Zona Pellucida-Encapsulated Islets for Sustained Glycemic Control in Immunocompetent Mice Cell encapsulation is the process of immobilizing cells within a semipermeable polymerAttorney Docket No.11196-120WO1 hydrogel. Recent advancements in the development of biocompatible polymers and the enhancement of angiogenesis have significantly advanced this technology. Since the polymer hydrogel serves to shield encapsulated cells from environmental damage, increasing hydrogel thickness enhances cell protection. Indeed, a growing body of evidence suggests that hydrogel capsules with 1.5 mm diameters can protect insulin-releasing b cells, allowing animals to remain free of hyperglycemia for an extended period. However, large capsules pose challenges such as high transplantation volumes and limited molecular transport. In contrast, while thin capsules do not face these issues, they often fail to provide sufficient cell protection in vivo. Immunocompetent diabetic animals transplanted with cells in thin capsules typically did not maintain normoglycemia beyond one month. Consequently, the current mainstream strategy in cell encapsulation and delivery is on developing large hydrogel capsules. Mammalian eggs are surrounded by a delicate compartment known as the zona pellucida consisting of glycoproteins. The zona pellucida in mature human eggs is typically 10 to 30 µm thick. Once the egg is triggered by a sperm cell for fertilization, Ca2+ions and enzymes quickly induce glycoprotein cleavage, assembly, and crosslinking on the egg surface. These biochemical reactions result in the hardening of the zona pellucida, which prevents additional sperms cells from entering the fertilized egg and acts as a protective shield during embryo development. This biological process has been emulated to develop a thin biomimetic zona pellucida (BZP) on the membranes of mammalian cells (FIG. 1A). Aptamers are inserted into the cell membrane for displaying a serine protease enzyme (i.e., thrombin). In the presence of Ca2+, the enzyme catalyzes the cleavage and assembly of fibrinogen, facilitating the rapid formation of fibrin surrounding the cell membrane. The fibrin meshwork absorbs alginate that is further crosslinked by Ca2+and a polypeptide (i.e., polylysine). The entire process of BZP development is device-free, droplet-free, and stress-free, spontaneously taking place in aqueous solutions under physiological conditions without any harsh physical, chemical, or biological factors. Results Evaluation of molecular recognition and biomolecule crosslinking: The development of BZP began with the decoration of the cell membrane with the serine protease thrombin using aptamers. Aptamers are single-stranded oligonucleotides selected from a large pool of DNA or RNA molecules. In this study, three DNA aptamers (Apt-1, Apt-2, and Apt-3) were assessed in binding to thrombin. All of them exhibited the capability of binding thrombin as determined by the assays of microparticle binding and electrophoretic mobility shift (FIG. 1B and 5A). Two types of aptamers are identified during the process of aptamer selection. One has the ability to bind target molecules without neutralizing them, while the other not only binds but alsoAttorney Docket No.11196-120WO1 neutralizes the target molecules. As the purpose of the study is to display aptamers for enzymatic catalysis activity rather than blocking enzyme activity, additional analysis was conducted on the proteolytic function of thrombin in the presence of aptamers. The results indicate that Apt-1 substantially inhibited thrombin activity, whereas the other two had a minimal or little effect on thrombin activity (FIG.5B). The study used microparticles as a simple cell model to examine the display, retention, and bioactivity of aptamer-bound thrombin on the surface. The data show that the immobilized aptamers could bind and display thrombin on the microparticle surface (FIG. 1C). The bound thrombin could maintain a long retention half-life that was approximately 3 hours (FIG. 1D). Importantly, the aptamer-bound thrombin exhibited high bioactivity, suggesting that the aptamer did not neutralize thrombin or block its enzymatic catalysis activity. The apparent bioactivity half-life of thrombin on the microparticle surface gradually decreased with time, which is consistent with the dissociation of thrombin from the aptamers. The synthesis of fibrin and the crosslinking of fibrin, alginate, and polylysine in the presence of Ca2+was further examined. Fibrinogen is a naturally occurring glycoprotein susceptible to cleavage by thrombin. In the presence of Ca2+and thrombin, fibrinogen undergoes rapid cleavage and assembly. Thus, the conversion of fibrinogen to fibrin was used to replicate the initial stage of the zona pellucida formation. Fibrin exhibited a mesh-like structure with fibrils (FIG. 1E), which is similar to the natural zona pellucida. As fibrin was highly porous, it would allow the penetration and absorption of alginate. After alginate treatment and crosslinking with Ca²^, the structure of fibrin changed significantly and exhibited a smaller pore size (FIG. 1F). Further addition of polylysine did not show significant structure change (FIG. 6E). The numerical simulation showed that alginate could rapidly penetrate fibrin by 20 µm within 30 minutes (FIG. 6A). This result was confirmed by fluorescence imaging of the alginate-treated fibrin hydrogel (FIG.6B). Three crosslinking reactions were involved during the formation and hardening of the BZP, including fibrin-alginate crosslinking, alginate-Ca2+crosslinking, and alginate-polylysine crosslinking. The fibrin was crosslinked with alginate through click chemistry since fibrinogen and alginate had dibenzocyclooctyne (DBCO) and azide groups, respectively. The gel electrophoresis image reveals a strong fluorescence band, indicating robust chemical crosslinking between fibrinogen-DBCO and alginate-azide (FIG. 6C). Alginate was also crosslinked through ionic interactions between the carboxylate groups and Ca2+to form an alginate hydrogel. Alginate was further crosslinked with polylysine through polyelectrolyte complexation since these two molecules have opposite charges. With these crosslinking reactions, the properties of the BZP would be tuned by simply varying the concentrations of alginate and polylysine.Attorney Docket No.11196-120WO1 Moreover, the observed enhancement in both storage and loss moduli of fibrin suggests that the crosslinking reactions contribute to the hardening of the BZP (FIG. 6D). Notably, all the three crosslinking reactions took place in aqueous solutions without the need for any instruments or droplet generation. Additionally, they did not involve any harsh biological, chemical, or physical stress factors such as low pH, organic solvent, shear stress, or free radicals. Evaluation of BZP development: To understand the rate of aptamer binding onto a surface, the microparticles were incubated in the aptamer solution and monitored the time- dependent process of aptamer adsorption onto microparticle surfaces (FIG. 7). The aptamers were labeled with FAM-labeled complementary sequences for microscopic visualization. Fluorescence analysis revealed that aptamer adsorption onto the microparticle surface reached a plateau within 10 to 15 minutes. The concentration-dependent aptamer adsorption onto microparticle surfaces was also examined. The aptamer adsorption increased with the aptamer concentration and reached a plateau at 0.5 µM. Accordingly, the density of displayed thrombin on the microparticle surface increased with aptamer adsorption. After thrombin immobilization, the microparticles were incubated in Cy5-labeled fibrinogen solution (FIGS. 8A-8D). The images show that fibrin formed on the microparticle surface. The uniformity of fibrin increased with the increase of fibrinogen concentration. The microparticles were further immersed in the alginate solution. The diffusion of alginate was a function of time. Initially, alginate molecules were predominantly located at the interface of the solution and fibrin. By one hour, most regions of the fibrin became saturated with alginate molecules (FIG. 8E). The experimental measurement was consistent with the simulation (FIG. 6A). Finally, the microparticles were treated with the mixture of Ca2+and polylysine and examined under the confocal microscope (FIG. 8F). Microparticles exhibited strong Cy3 fluorescence signals, indicating the stable alginate-polylysine crosslinking. The signals of fibrin, alginate, and polylysine overlapped on the microparticle surface, confirming the formation of the BZP through the three reactions in aqueous solutions. The quantification of the varying zeta potential step by step was consistent with the microscopic assessment (FIG. 8G). Notably, for each step of reaction, microparticle aggregation was not observed. After demonstrating BZP formation, the study evaluated the uniformity of the BZP by examining the fluorescence distribution of a focal plane (FIG.2B). Three symmetrical lines were drawn across the center of the plane at three arbitrary angles. The three profiles of fluorescence intensity were virtually the same, suggesting that the BZP was uniformly formed on the microparticle surface. The BZP was further evaluated in the x-y, y-z, and x-z projections (FIG. 2C). A series of images on multiple focal planes were captured throughout the depth of the microparticle and compiled them into a Z-stack image. The spatial visualization furtherAttorney Docket No.11196-120WO1 confirmed the uniformity of the BZP. The average line profiles further confirmed that the fluorescence signals mainly came from the surface of the microparticles (FIG. 8H). The same protocol was applied to three microparticles with different sizes (FIG. 8I). The BZP could develop on the surfaces of these microparticles, suggesting that the formation of BZP was not influenced by the size of the microparticles. Next, BZP development on the membranes of living cells was studied. Multiple types of homotypic and heterotypic cell clusters were tested. Mesenchymal stem cells (MSCs) and MCF7 cells were used to prepare two homotypic cell clusters, respectively (FIG. 2E). MSCs, human umbilical vein endothelial cells (HUVECs), MDA-MB231, and NIH / 3T3 were used to prepare two heterotypic cell clusters (FIG. 2F). The process used for the BZP development on these cell clusters was the same as that on the microparticles except that the cell clusters were first treated with cholesterol-conjugated thrombin aptamer for aptamer display on the cell membrane. The confocal microscopy images show that BZP was developed on the surface of all the spheroids. The average thickness was approximately 20 µm (FIGS. 9A-9B), similar to the ZP of a mature human egg. In addition to these spheroids with a nearly perfect spherical shape, it was examined if the same concept could be applied to irregular shapes or geometries. To this end, two, three, and four spheroids were purposely fused together to prepare spheroid dimers, trimers, and tetramers, respectively. The images show that BZP could be developed on these spheroid multimers (FIG. 2G). In addition to these regular or irregular cell spheroids, BZP on the surface of pancreatic islets was developed. Islets, composed of ^, ^, ^, ^, and endothelial cells, are used as the example of naturally heterotypic cell clusters. Consistent with synthetic spheroids, BZP was developed on the surface of islets (FIG. 9C). Therefore, the data show that BZP can be created on the cell membrane regardless of cell type, shape, or geometry. Characterization of BZP in molecular permeability and stability: The zona pellucida is a barrier that regulates the permeability of molecules. Small molecules can easily penetrate the zona pellucida whereas those with certain high molecular weights cannot. The study assessed the permeability of the BZP by incubating MSC spheroids in the FITC-dextran solution for observation (FIGS. 3A and 15A). The BZP exhibited selective permeability. It allowed the free diffusion of 4 kDa dextran. As the molecular weight increased to 70 kDa, a corresponding gradual decrease in permeability was observed, reaching a point of impermeability at 250 kDa. The selective permeability characteristic of BZP was further evidenced through the observed diffusion of molecules into fibrin hydrogels (FIG. 15B). Additionally, the diffusion profiles of FITC-dextran across the Transwell system further supported these findings (FIG. 15C). To further assess the molecular transport across BZP, antibody binding to MSC surface markers was examined. In uncoated MSC spheroids, antibodies targeting CD73 and CD90 successfullyAttorney Docket No.11196-120WO1 recognized and bound to the cell surface (FIG. 15D). However, in BZP-coated spheroids, antibody binding was significantly reduced, demonstrating the selective permeability of the BZP encapsulation. This observation was further supported by incubating fluorescently labeled antibodies with the spheroids: uncoated spheroids displayed strong FITC signals, whereas BZP- coated spheroids exhibited markedly diminished fluorescence, reinforcing the selective permeability of the BZP coating. The zona pellucida also acts as a barrier that prevents a fertilized egg from attaching to the uterine wall too early. The study assessed the function of the BZP in preventing cell attachment to the surrounding substrate by incubating MSC spheroids in a cell culture plate. While most cells in the native MSC spheroids spread on the plate surface during the 72-h incubation, the BZP-coated spheroids could maintain their original shape and morphology without any sign of attaching to or spreading on the plate surface (FIG. 3B). The function of the BZP in maintaining the shape of MSC spheroids was also evaluated by vigorous vortex. The BZP-coated spheroids could maintain their original shape after vortex compared to untreated spheroids that were completely dissociated (FIG.3C). Examination of cell functions: The entire process of BZP development did not involve any harsh factors such as low pH, organic solvent, free radicals, or shear stress. Therefore, it was expected that BZP development would not affect cell functions. With MSC spheroids as a model, cell viability was studied. The live / dead staining showed that BZP-coated MSCs exhibited the same staining pattern as the native MSCs, which was consistent with the analysis of ATP and metabolic activity (FIG. 3D). These data suggest that cells could maintain high viability after BZP development on the cell membrane. The levels of human cytokines show a minimal difference between coated and uncoated spheroids, indicating that BZP development did not affect the ability of MSCs in producing cytokines (FIG. 3E). It was further confirmed by the examination of vascular endothelial growth factor (VEGF) secretion from the cell spheroids using ELISA (FIG. 3F). MSCs have the ability to differentiate into various cell types, including osteoblasts, chondrocytes, and adipocytes. This differentiation potential is one of the key functions of MSCs. BZP-coated and uncoated MSCs exhibited similar differentiation potential into osteogenic, chondrogenic, and adipogenic lineages, indicating that BZP development did not alter their differentiation potentials (FIG. 10). Therefore, the results demonstrate that BZP development on the cell membrane does not affect cell functions. In vivo assessment of BZP in cell delivery and protection: After developing and characterizing the BZP, islet transplantation was used as an example to demonstrate the use of the BZP in biomedical applications. Islets embedded in a thick hydrogel particle have been intensively studied as an immunoisolation tool to treat type 1 diabetes. However, the large sizeAttorney Docket No.11196-120WO1 not only restricts molecular transport from supporting cell survival, but also limits an organ’s ability to receive and accommodate a large number of islets. This limitation becomes even more pronounced when multiple transplantations are required. Therefore, using the thick hydrogel particle to deliver islets in the clinic may be challenging. The BZP can solve this problem as it has a much smaller polymer volume (FIG.16). As foreign materials or cells have a high probability of inducing strong foreign body response, it was examined if the BZP can reduce the level of this response using polystyrene microparticles as a model. Both uncoated and BZP-coated microparticles were injected into the peritoneal cavities of mice and intraperitoneal fluids were collected on day 1 and day 7 for the analysis of cytokines (FIGS. 4A-4B). The level of IL-6 on day 1 increased by approximately 6 times in the uncoated microparticle group rather than the coated group. Uncoated microparticles were also found to induce the increase of TGF-^1 level by nearly 30 times on day 7. The level of TGF-^1 in the coated microparticle group was much lower than that in the uncoated microparticle group. This difference indicates that the BZP could reduce the level of the foreign body response caused by the microparticles. An in vitro immunoisolation assay was also used to examine the protective effects of BZP against immune-mediated cell attack (FIG. 12A). The uncoated spheroids were lysed by the immune cells during the 24 hours cell co-culture whereas the BZP-coated ones were virtually intact. It indicates that the BZP could shield the encapsulated cells from the immune attack. To illustrate the applications of the BZP approach, pancreatic islets were coated with BZP and examined their functions both in vitro and in vivo. The live / dead staining showed that the islets maintained high viability after BZP development (FIG. 4C), which is consistent with the previous analysis using MSC spheroids. Both uncoated and BZP-coated islets showed normal glucose-stimulated insulin secretion (GSIS) (FIG. 4D; left). Their stimulation indices were 4.6 ± 1.1 and 4.3 ± 0.8, respectively (FIG. 4D; middle). Their delta values were 38.0 ± 11.5 and 27.9 ± 4.2 pmol per 100 islet equivalents (IEQs), respectively (FIG. 4D; right). The stimulation indices and delta values have no statistically significant difference between uncoated and coated islets. These results suggest that islets can maintain their normal functions as the BZP development is a stress-free process. The study also examined the apoptosis of islets exposed to proinflammatory cytokines. The BZP-coated islets exhibited a reduced degree of susceptibility to proinflammatory cytokines compared to uncoated islets (FIG.12B). The in vivo function of BZP-coated islets were further examined by delivering them into the peritoneal cavity of diabetic mice (FIG. 4E). Intraperitoneal glucose tolerance tests (IPGTT) were conducted on day 20 and day 60 post transplantation of islets (FIGS. 4F-4G and FIG. 19A-19B). The IPGTT results indicate that mice transplanted with BZP-coated islets showedAttorney Docket No.11196-120WO1 faster glucose clearance than diabetic mice or the uncoated islet group. Notably, the BZP group restored normoglycemia at a glucose level similar to that in healthy mice on day 20. The increased serum rat C-peptide level could be detected in the blood of mice treated with BZP- coated islets (FIG. 4H and FIG. 19C). The C-peptide levels were consistent with the IPGTT measurement results. Mice transplanted with uncoated islets showed an average level of blood glucose increased to 316 mg / dL on day 9, and their glucose level was never lower than 200 mg / dL (FIG. 4I). Moreover, it quickly rose after day 12. In contrast, the BZP-coated islets could reduce the glucose level below 200 mg / dL on day 6. The 60-day area under the curve for the uncoated group was more than 2-fold as high as that for the BZP-coated group (FIG. 4J). Mice in the BZP-coated group showed significantly higher normoglycemic mice percentage, maintaining 80% of mice normoglycemic up to day 66 while uncoated group failed to restore normoglycemia after transplantation (FIG. 4K). In the BZP group, one mouse started to have a consistently increasing blood glucose readings over 250 mg / dL after day 30, maintaining normoglycemia up to day 27 (FIG. 4I). The other three diabetic mice could maintain normoglycemia up to day 66, 84, and 87. Notably, one mouse could maintain normoglycemia over 100 days. The BZP group showed stable body weights similar to healthy mice and a higher survival rate compared with the naked islet group (FIGS.4L and 4M). It is important to note that in these animal studies, regular alginate without specific ultra- purification or chemical modification was used to demonstrate the concept of developing BZP. Previous studies showed that ultrapure or modified alginate offered high biocompatibility. Therefore, the synthesis of BZP using chemically modified ultrapure alginate was also studied (FIG. 17A). The adsorption of proteins on the transplanted cell surface is the initial step in a foreign body response, which ultimately impacts the cell viability and graft survival. BZP synthesized with the zwitterionically modified ultrapure alginate (BZP-M) showed significantly reduced adsorption of BSA and lysozyme compared with BZP synthesized with unmodified regular alginate (BZP-U) by 3-fold and 8-fold, respectively (FIG. 17B). Furthermore, the data indicates that BZP-M mitigated the foreign body response, as evidenced by a 4-fold decrease in TGF-^1 and IL-10 expression on day 7 post transplantation (FIG.17C). Next, an allogeneic islet transplantation study was conducted to compare BZP-M and BZP-U. In this experiment, mouse islets obtained from CD-1 mice were encapsulated. Dithizone staining and scanning electron microscopy (SEM) micrographs confirmed the quality of pancreatic islets and successful BZP formation on the cell surface, respectively (FIGS. 17D- 17E). Forty days post the in vivo transplantation (FIG. 14A), the IPGTT test demonstrated that the BZP-M group exhibited faster intraperitoneal glucose clearance compared to the BZP-UAttorney Docket No.11196-120WO1 group (FIG. 14B). Both BZP-U and BZP-M groups showed increased serum C-peptide levels in the blood of mice after glucose injection, indicating that the transplanted islets were functional (FIG.14C). In the BZP-U group, two out of five mice began to exhibit hyperglycemia on day 48, while additional mice developed hyperglycemia by day 57 and day 72 (FIGS. 14D-14E). In contrast, only one mouse in the BZP-M group started to exhibit hyperglycemia at day 63 post islet transplantation. Six out of seven mice maintained normoglycemia for over 60 days, with five remaining normoglycemic for more than 100 days. In the BZP-M group, all the immunocompetent diabetic mice maintained normoglycemia up to day 60 with the average blood glucose level below 250 mg / dL (FIG. 8A). The 60-day area under the curve for the BZP-M group was significantly lower than the BZP-U group (FIG.18B). Discussion Cell therapy has demonstrated great potential in various applications such as diabetes treatment, regenerative medicine, and immunotherapy. However, mammalian cells are fragile, requiring sufficient protection to maintain their functions. While bulk hydrogels or large capsules are often used for this protection, larger dimensions present two major challenges. The first one is limited molecular diffusion, which can lead to cell death or functional loss due to insufficient oxygen, nutrient, and waste transport. Large capsules also increase the transplantation volume in vivo. High polymer-to-cell volume ratios restrict cell transplantation to organs like the liver, which can be exacerbated by the need for repeated transplants. This is particularly relevant for diabetes treatment, as transplanted islets or ^ cells do not last indefinitely, and cell transplantation would need to be repeated. The BZP approach is promising to solve these issues. For example, when a 20 ^m thick BZP is compared to a 500 ^m microcapsule for coating a 100 ^m islet, the former has only 1 / 71 the polymer volume of the latter. Consequently, if the polymer volume is considered, islets coated with a 20 ^m thick BZP can be transplanted into an organ 70 times more than those with 500 ^m microcapsules after the functional cells have disappeared. The BZP approach is both equipment-free and droplet-free. Islets exhibit heterogeneity in size and geometry, which may cause issues to methods that rely on solution flow through channels with fixed dimensions. The BZP approach operates independently of islet size or geometry. Furthermore, being droplet-free, the BZP approach ensures 100% cell encapsulation efficiency and avoids the Poisson distribution that can lead to the formation of empty capsules or capsules containing varying numbers of islets. It is also important to highlight the encapsulation conditions of the BZP approach. Mammalian cells, such as ^ cells, are highly fragile and can be easily damaged by high shear stress, low pH, free radicals, or organic solvents. The BZPAttorney Docket No.11196-120WO1 approach operates entirely in aqueous solutions under physiological conditions, ensuring the process remains free from physical, chemical, or biological stress factors. This BZP approach, counterintuitively, highlights the potential of developing thinner capsules rather than thicker or larger ones for cell immunoisolation and protection. Developing BZP on the cell membrane presents a highly promising solution to the challenges of cell encapsulation without compromising cell bioactivity, functionality, and protection. Beyond cell delivery, this work on developing BZP may also drive progress across various fields, including biomimetic materials, regenerative medicine, synthetic biology, and even the study of life's origins. Materials and Methods Chemicals and reagents. All the DNA sequences were obtained from Integrated DNA technologies (Coralville, IA). The detailed information of DNA sequences is shown in Table 1. Dibenzocyclooctyne-PEG4-NHS ester (DBCO-PEG4-NHS), DBCO-AF488, biotin-Cy5, and Azide-Cy5 were purchased from Click Chemistry Tools (Scottsdale, AZ). Di-tert- butyldicarbonate, N,N-dimethylethylenediamine, thrombin from human plasma, biotinylated thrombin, fibrinogen from human plasma, thrombin activity fluorometric kit, streptozotocin, sodium alginate (medium viscosity, 80-120 kDa), PRONOVA® UP VLVG (>60% G, MW < 75 kDa), O-(2-Aminoethyl)-O’-(2-azidoethyl)pentaethylene glycol (NH2-PEG6-N3), calcium chloride (CaCl2), dithizone, Annexin V-FITC Apoptosis Detection Kit, FITC-dextran (4 kDa, 20 kDa, 70 kDa, and 250 kDa), Krebs Ringer Bicarbonate (KRB) buffer, Glucose, 2-chloro-4,6- dimethoxy-1,3,5-triazine (CDMT), N-methylmorpholine (NMM), and Amicon Ultra Centrifugal Filters (10K, 50K, 100K MWCO) were obtained from Sigma Aldrich (St. Louis, MO). Float-A- Lyzer G2 10 kD MWCO membrane was obtained from Repligen (Waltham, MA). SYBR gold DNA dye, Tris-borate-EDTA buffer (10×), FITC-labeled BSA, and Hoechst 33342 were purchased from Thermo Fisher Scientific (Waltham, MA). CellTiter 96® AQueous One Solution Cell Proliferation Assay and CellTiter-Glo® Luminescent Cell Viability Assay were obtained from Promega (Madison, WI). PEGylated polylysine (26 kDa) was purchased from Nanosoft Polymers (Lewisville, NC). Cy3-labeled polylysine and FITC labeled lysozyme were purchased from NANOCS (New York, NY). Streptavidin-coated polystyrene microparticles were purchased from Spherotech (Lake Forest, IL). Live / Dead viability staining kit, Streptavidin, Alexa Fluor™ 488 NHS Ester (Succinimidyl Ester), CFSE dye, biotinylated thrombin, and CellTrace Far Red Cell Proliferation Kit were purchased from Invitrogen (Carlsbad, CA). Ultra- low attachment spheroid microplates and Transwell® polycarbonate membrane cell culture inserts were purchased from Corning (Corning, NY). Hanks' balanced salt solution (HBSS),Attorney Docket No.11196-120WO1 TrypLE Express Enzyme, and Geltrex™ LDEV-Free Reduced Growth Factor Basement Membrane Matrix were purchased from Gibco (Billings, MT). Rat Ultrasensitive Insulin ELISA kit was purchased from Crystal Chem (Elk Grove Village, IL). Rat C-Peptide ELISA kit, and Mouse C-Peptide ELISA kit were purchased from ALPCO (Salem, NH). Human vascular endothelial growth factor (VEGF) ELISA kit, recombinant murine TNF-^, IL-1^, IFN-^, murine IL-6 ELISA Kit, murine TNF-^ ELISA Kit, and murine IL-10 ELISA Kit were purchased from PeproTech (Cranbury, NJ). Human Cytokine Array C5 and Murine TGF-^1 ELISA kit were purchased from RayBiotech (Peachtree Corners, GA). Human adipocyte differentiation medium, human chondrocyte differentiation medium, and human osteoblast differentiation medium were obtained from Cell Applications (San Diego, CA). Examination of aptamer-thrombin binding using microparticle binding assay, electrophoretic mobility shift assay (EMSA), and thrombin proteolytic activity assay. Streptavidin-coated microparticle in 5 µm size was used for the assay. Microparticles (20 µL in DPBS, 0.5% w / v) were mixed with biotinylated thrombin solution (0.5 µg) for 1 hour at room temperature. Then, the microparticles were centrifugated (300 × g, 3 min) and washed with DPBS twice. The microparticles were resuspended in binding buffer (400 µL, 5 mM MgCl2, 1 mM CaCl2, and 2.5 mM KCl in 1×PBS) and mixed with FAM labeled aptamer (2.5 µM) for 1 hour at room temperature. The resulting microparticles were washed twice with binding buffer and the fluorescence intensities captured by Attune NxT Flow Cytometer (Thermo Fisher Scientific) were analyzed using FlowJo software. For the EMSA analysis, thrombin solution (1 µg, in binding buffer) was mixed with DNA aptamers (100 ng) and incubated 30 minutes at room temperature. The thrombin-aptamer complexes were analyzed using electrophoresis by running the samples in 12% polyacrylamide gel at 90 V for 45 minutes at room temperature. The DNAs in the gel were further stained with SYBR gold for 15 minutes and the images were recorded using CRI Maestro EX System (Woburn, MA). Fluorescence signal intensities of the thrombin bound aptamer portion were analyzed and compared using ImageJ software. For the thrombin enzymatic activity assay after binding, thrombin solution (1 µg, in binding buffer) was mixed with DNA aptamers (1 µM) and incubated 30 minutes at room temperature. Thrombin proteolytic activity was examined using the thrombin activity fluorometric assay kit according to the manufacturer’s protocol. Preparation of azide-modified alginate and DBCO-conjugated fibrinogen. Sodium alginate 100 mg was dissolved in MES buffer (5 mL, 50 mM, pH = 5). NHS (14 mg), EDC (116 mg) and NH2-PEG6-N3 (28 mg) were further added to this solution and stirred for 30 minutes at room temperature. Then, NaOH (55 µL, 6 M) was added to the solution to adjust pH to 7.5-8.0 and incubated overnight. Membrane with 10K MWCO was used for dialysis purification againstAttorney Docket No.11196-120WO1 water for 3 days. The resulting alginate-N3solution was then precipitated in cold acetone, mixed with DI water, and lyophilized. For the synthesis of alginate-AF488, alginate-N3solution (200 µL, 1% w / v) was mixed with DBCO-AF488 (12 µL, 5 mM) and allowed to react on shaker for 4 h. The product alginate-AF488 was collected and purified using an Amicon Ultra Centrifugal Filter (100K MWCO). Fibrinogen solution (400 µL, 50 mg / mL) and DBCO-PEG4-NHS ester (75 µL, 30 mM in DMSO) was added to 600 µL of modification buffer (50 mM NaHCO3 in DPBS) and allowed to react on shaker for 4 h. For the synthesis of fibrinogen-Cy5, fibrinogen-DBCO solution (200 µL, 40 mg / mL) was further mixed with Azide-Cy5 (10 µL, 5 mM) and allowed to react on shaker for 4 h. The products fibrinogen-DBCO or fibrinogen-Cy5 was purified using an Amicon Ultra Centrifugal Filter (50K MWCO). Simulation of alginate diffusion into fibrin hydrogel matrix. COMSOL Multiphysics v.6.0 was used to simulate the diffusion of alginate molecules into fibrin (Fb) hydrogels. In constructing the bulk Fb hydrogel model, a disk-shaped model with diameters of 200 µm and 50 µm on the height was designed. The diffusion of molecules into the hydrogel was assumed to be 1-dimensional with presuming the initial alginate concentration in the solution above the hydrogel to be 25 µM. Bottom layer was assumed to be nearly impermeable, closely mimicking the actual cell surface. Initial concentration of alginate inside the Fb hydrogel was presumed to be zero. The simulation ran continuously for 60 minutes, and measurements were recorded at 30- minute intervals. In the models, the diffusion coefficient was set to 10-8cm² / s to simulate alginate movement within the hydrogel matrix. Examination of diffusion and conjugation of alginate. To assess alginate diffusion into the Fb hydrogel matrix, fibrinogen solution (10 mg / mL) was mixed with thrombin (1 U / mL) and incubated in a mold for 30 minutes at 37oC to form a Fb hydrogel. Alginate-AF488 solution (0.25% w / v) was put on top of the Fb hydrogel and allowed to diffuse in for 1 h. After the incubation, cross-section of the hydrogel middle part was cut, and the fluorescence microscopic images were obtained using Olympus IX73 inverted microscope. To chemically conjugate fibrinogen to alginate, fibrinogen-DBCO solution (10 mg / mL) was mixed with alginate-AF488 (1% w / v) and allowed to react for 1 h. To examine the fibrinogen-alginate conjugation, native polyacrylamide gel electrophoresis (native PAGE) was used. The gel electrophoresis was run at 80 V for 45 minutes and the gels was imaged using CRI Maestro EX System (Woburn, MA). Formation and characterization of fibrin-alginate-polylysine matrix. Fb hydrogel was formed by mixing fibrinogen (10 mg / mL) and thrombin (1 U / mL) at 37oC. For fluorescent imaging, low concentration of fibrinogen (2.5 mg / mL) was used. After Fb hydrogel formation, mixture of sodium alginate solution (0.125% w / v) and alginate-azide solution (0.125% w / v) was added and incubated for 1 hour at room temperature. Alginate-embedded Fb hydrogel was addedAttorney Docket No.11196-120WO1 with polylysine (0.05% w / v) supplemented calcium chloride solution (CaCl2, 50 mM) for 5 min. Finally, sodium alginate solution (0.05% w / v) was added for further crosslinking. The detailed structures of Fb hydrogel, fibrin-alginate (Fb / Al) hydrogel, and fibrin-alginate-polylysine (Fb / Al / PLL) hydrogel were examined using Zeiss SIGMA VP-FESEM (SEM) and Olympus Fluoview 3000. To examine the rheological properties of the hydrogel, specifically the storage modulus and loss modulus, oscillation strain and angular frequency were systematically varied. The rheological measurements were conducted using TA-instrument Discovery HR-2 rheometer. Every test was conducted using a parallel plate with a 20 mm diameter and a 200 µm gap under ambient conditions. Typically, frequency sweep experiments were performed within the range of 1.0 to 50 radians per second (rad s-1) at a 0.5% strain, while amplitude sweep experiments covered a strain range from 1.0% to 50% at a frequency of 1.0 rad s-1. Synthesis of zwitterionic sulfobetaine. N,N-dimethylethylenediamine (3.61g) was dissolved in chloroform (50 mL). Di-tert-butyl dicarbonate (9.17g) was added dropwise on ice bath (0oC) and stirred overnight at room temperature. After removing the solvent by evaporation under vacuum, ethyl acetate was added (30 mL) to the solid product and separated using a funnel. Then, anhydrous sodium sulfate added and filtered through the filter funnel, and the solvent was removed by evaporation under vacuum. After adding propane sultone (6 g) and toluene (50 mL) to the solid product, the solution was stirred for 4 hours at 60oC and the precipitate was collected using a vacuum filter. The precipitate was rinsed with hexane and vacuum dried. After methanol (30 mL) was added, 10% HCl / Methanol (30 mL, 1.25 M) was added dropwise at 0oC. The mixture was stirred for overnight at room temperature. Zwitterionic sulfobetaine was obtained by removing the solvent from the mixture by centrifugation, followed by vacuum drying. Synthesis of zwitterionic sulfobetaine modified alginate. VLVG alginate (200 mg) was dissolved in mixture solvent (50 mL, 40 mL of DI water and 10 mL acetonitrile). 2-chloro-4, 6- dimethoxy-1, 3, 5-triazine (CDMT, 90 mg), N-methylmorpholine (NMM, 112 µL), and sulfobetaine (180 mg) in DI water (10 mL) were added to the solution and stirred overnight at 60 °C. The solvent was removed by vacuum drying. The solid product was dissolved in DI water. The solution was filtered through a 0.22 µm filter. Then, the solution was dialyzed against 10,000 MWCO membrane in DI water for three days. Zwitterionic sulfobetaine-modified alginate was obtained by freeze-drying. The modification of alginate was analyzed through 400 MHz1H NMR using Bruker NEO-400 (Billerica, MA). Thrombin immobilization on the microparticle surface. First, streptavidin-coated microparticles were washed twice with DPBS. The microparticles were incubated with biotinylated DNA aptamers at room temperature for 15 minutes on a rotator. For examination of DNA aptamer decoration on microparticle surface, FAM-labeled complementary sequences wereAttorney Docket No.11196-120WO1 used to visualize DNA aptamer in confocal microscopic imaging. After washing twice with DPBS, microparticles were mixed with thrombin solution at room temperature for 15 min. The microparticles were washed with DPBS twice before further use. The number of aptamers decorated on the surface was measured using the fluorescently labeled DNA aptamer complementary sequence. The loading amount of immobilized thrombin on the microparticle surface was calculated by analyzing the amount of unloaded thrombin. The enzymatic activity and retention of immobilized thrombin were analyzed using thrombin activity fluorometric assay kit according to the manufacturer’s protocol. Fluorescently labeled thrombin was synthesized by conjugating AF488 NHS ester with thrombin. Briefly, thrombin solution (10 µg / mL) was incubated with AF488 NHS ester (5 mM, in DMSO) for 2 hours at room temperature. The resulting fluorescently labeled thrombin was purified using Amicon Ultra Centrifugal Filters 10K MWCO. Development and characterization of biomimetic zona pellucida (BZP) on the microparticle surface. First, streptavidin-coated microparticles (200 µL) were washed twice with DPBS. The microparticles were incubated with biotinylated DNA aptamers at room temperature for 15 minutes on a rotator. After washing twice with DPBS, microparticles were mixed with thrombin solution (1 U / mL) at room temperature for 15 minutes on a rotator. After washing twice, microparticles were mixed with fibrinogen-DBCO solution (10 mg / mL) for 10 minutes at 37oC with gentle pipetting. The formation of Fb hydrogel coating on the microparticle surface was examined using CRI Maestro EX System, Attune NxT Flow Cytometer, and Olympus Fluoview 3000. The microparticles were mixed with mixture of sodium alginate solution (0.125% w / v) and alginate-azide solution (0.125% w / v) at room temperature for 1 h. Then, polylysine (0.05% w / v) supplemented calcium chloride solution (50 mM) was added and incubated for 5 min. Finally, alginate solution (0.05% w / v) was mixed and incubated for 5 min. Confocal laser scanning microscopy was used to demonstrate the formation of biomimetic zona pellucida on the microparticle or spheroid surface. All the confocal microscopic images were z-positioned to focus the plane through the center of the spherical shape unless notified. To assess the uniformity of BZP coating, line profiles from confocal images of 65 microparticles were examined. Malvern Zetasizer Nano ZS was used to analyze the step-by-step zeta potential change of the encapsulated microparticles (5 µm diameter). Protein adsorption. BZP (BZP synthesized using regular alginate), UP-BZP (BZP synthesized using ultrapure alginate), or BZP-M (BZP synthesized using zwitterionically modified ultrapure alginate) coated microparticles (5 µm diameter, 20 µL in DPBS, 0.5% w / v) were immersed in FITC-labeled BSA solution (1 mg / mL, in DPBS) or FITC-labeled lysozyme solution (1 mg / mL, in DPBS) for 1 hour at room temperature. After washing with DPBS toAttorney Docket No.11196-120WO1 remove the unbound molecules, the microparticles were analyzed using Attune NxT Flow Cytometer. The fluorescence intensities were normalized to BZP samples. Cell culture. Human bone marrow derived mesenchymal stem cell (MSC) was purchased from ATCC (Manassas, VA) and maintained in low glucose DMEM supplemented with 10% FBS. MCF-7, MDA-MB231, and NIH / 3T3 were purchased from ATCC (Manassas, VA) and maintained in DMEM supplemented with 10% FBS. Human umbilical vein endothelial cell (HUVEC) was purchased from ATCC (Manassas, VA) and maintained in recommended growth medium (ATCC). Natural killer cell (NK-92MI) was obtained from ATCC (Manassas, VA) and maintained in Alpha modification of Minimum Essential Medium (^MEM) supplemented with 0.2 mM inositol, 0.1 mM 2-mercaptoethanol, 0.02 mM folic acid, 12.5% FBS, and 12.5% horse serum. Rat islets (Joslin Diabetes Center at Harvard Medical School, Boston, MA) were maintained in RPMI 1640 with L-Glutamine (Gibco #11875–093) supplemented with 10% FBS, penicillin (100 U / mL), and streptomycin (100 ^g / mL). Mouse islets from CD-1 mouse were obtained from University of Pennsylvania (Philadelphia, PA) and maintained in RPMI-1640 media with 10mM glucose supplemented with 10% FBS, penicillin, and streptomycin. All the cells were maintained in 37 °C incubator in an atmosphere of 5% CO2and relative humidity of 95%. Formation of cell spheroids. MSC spheroids and MCF7 spheroids were generated by seeding in ultra-low attachment 384 well plate (5 × 103cells per well) with centrifugation (50 × g, 5 min). MSC:HUVEC spheroids and MDA-MB231:3T3 spheroids were generated by mixing two cell types in a ratio of 1:1 and seeding in ultra-low attachment 384 well plate (5 × 103cells per spheroid). For the fusion of spheroids to form different structures, multiple MSC spheroids (2 / 3 / 4 spheroids, 5 × 103cells per spheroid) were incubated together in a well and incubated for 12 hours in incubator before used. Development and characterization of BZP on the cell membrane. Cell spheroids or pancreatic islets were washed twice with DPBS and then incubated in cholesterol-conjugated DNA aptamer solution at room temperature for 15 minutes on a rotator. After washing twice with DPBS, cell spheroids were mixed with thrombin solution (1 U / mL, in DPBS) at room temperature for 15 min. After another washing with DPBS, fibrinogen-DBCO solution (10 mg / mL, in DPBS) was added and incubated for 10 minutes at 37oC. Fb hydrogel coated cell spheroids were further mixed with alginate solution (alginate-azide + alginate, 0.25% w / v) at room temperature for 1 hour on a rotator. Then, polylysine (0.05% w / v) supplemented calcium chloride solution (CaCl2, 50 mM) was added and incubated for 5 min. Finally, alginate solution (0.05% w / v) was mixed and incubated for 5 min. The resulting BZP on cell spheroid surface was imaged using Olympus IX50 phase contrast optical microscope and Olympus Fluoview 3000.Attorney Docket No.11196-120WO1 The thickness of BZP coating was measured using ImageJ software. Volumes of traditional alginate microcapsules and BZP coating for cell spheroid encapsulation were calculated using Eq.1 and Eq.2:where VTrad denotes the total volume of traditional alginate microcapsule, VBZP denotes the total volume of BZP coating encapsulating the cell spheroid, Dsph denotes the diameter of host cell spheroid, DTrad denotes the diameter of alginate microcapsule, and TBZP is the thickness of BZP coating on the cell spheroid surface. Specifically, the diameter of host cell spheroid (Dsph) was assumed to be 150 µm, the diameter of alginate microcapsule (DTrad) was varied from 0.5 mm to 1.5 mm, and TBZPwas set as 0.02 mm. Cell viability assessment. Cell viability was determined using the MTS assay, ATP assay, or the Live / Dead viability / cytotoxicity kit following the manufacturer's protocols. For the MTS assay, cells were cultured in complete growth medium containing 10% of 3-(4,5- dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) solution for 4 hours. Absorbance at 490 nm was measured using an Infinite M200 Pro microplate reader (Tecan; Grödig, Austria). For the ATP assay, CellTiter-Glo® 2.0 Reagent was added to the cell culture medium and incubated for 10 min. Luminescent signals were recorded using a microplate reader. In the case of the Live / Dead viability assay, cells were stained with 1 µM calcein-AM and 1 µM ethidium homodimer-1 solution for 15 minutes at 37°C in the absence of light. Stained cell spheroids were imaged using Olympus Fluoview 3000. Cytokine profiling. The cytokine antibody array was performed on MSC spheroids to examine 80 specific human cytokines in accordance with the manufacturer's instructions. Uncoated and BZP-coated MSC spheroids were seeded on 6-well plates (200 spheroids per well) and incubated in serum free medium. Supernatants were collected after 24 hours of incubation in serum-free medium. Following the blocking with a specific buffer, the membranes were exposed to sample solutions overnight at 4°C. Subsequently, after thorough washing, the membranes were incubated with a biotinylated antibody cocktail solution overnight at 4°C. Further washing steps were followed by incubation with HRP-streptavidin concentrate solution overnight at 4°C. Finally, the membranes were subjected to detection buffer treatment. The resultant images were captured and analyzed using the ChemiDoc MP Imaging System (Hercules, CA). Relative cytokine expressions were normalized by comparison with the control spots on the membranes. VEGF secretion from cell spheroids was further analyzed using enzyme-linked immunosorbent assay (ELISA) kit.Attorney Docket No.11196-120WO1 Osteogenesis, chondrogenesis, and adipogenesis of MSC spheroids. Uncoated and BZP-coated MSC spheroids were seeded on 6-well plates. Human osteoblast differentiation medium, human chondrocyte differentiation medium, and human adipocyte differentiation medium was added to the well for osteogenesis, chondrogenesis, and adipogenesis, respectively. Cell spheroids were incubated for 21 days with fresh media change every 2-3 days. For the osteogenesis analysis, cells were stained with Alizarin Red S solution (2% in deionized water). For the chondrogenesis analysis, cells were stained with Alcian Blue solution (1% in 3% acetic acid). For the adipogenesis analysis, cells were stained with Oil Red O solution (0.3% in deionized water). Cells were imaged using an inverted phase contrast microscope (Olympus IX50, Center Valley, PA). Examination of permeability, antibody transport across BZP, cell spreading, and physical protection. To examine the permeability of BZP coating on cell spheroids, MSC spheroids (2.5 × 103cells per spheroid) were incubated at room temperature with FITC-dextran solutions with different molecular weights (0.5 mg / mL in DPBS; 4 kDa, 20 kDa, 70 kDa, and 250 kDa). After 2 hours of incubation, resulting cell spheroids were imaged using Zeiss LSM 880 confocal laser scanning microscope. For the molecular diffusion test into bulk hydrogel matrices, Fb hydrogels and Fb / Al / PLL hydrogels were incubated at room temperature with FITC-dextran solutions (0.5 mg / mL in deionized water; 4 kDa, 20 kDa, 70 kDa, and 250 kDa) for 1 h. After washing twice with water, hydrogels were imaged using CRI Maestro EX System. For the diffusion test using Transwell system, Transwell inserts (6.5 mm diameter polycarbonate membrane, 0.4 µm pore size) were treated with fibrinogen-DBCO solution (10 mg / mL, in deionized water) for adsorption followed by thrombin solution (1 U / mL) treatment for Fb matrix formation. The resulting Fb matrix was sequentially treated with alginate-azide solution (0.25% w / v) and polylysine (0.05% w / v) supplemented calcium chloride solution (50 mM) to form Fb / Al or Fb / Al / PLL matrix on the Transwell inserts. Then, 200 µL of FITC-dextran solutions (0.5 mg / mL in deionized water; 4 kDa, 20 kDa, 70 kDa, or 250 kDa) were added on the apical side of the Transwell insert in a 24-well plate with 800 ^L of deionized water on the basolateral side. At predetermined time points (up to 8 hours), solutions were collected from the basolateral side and fluorescence intensities were measured using an Infinite M200 Pro microplate reader (Tecan; Grödig, Austria). Data were collected in triplicates. To assess molecular transport across BZP coating, MSCs or MSC spheroids were incubated at 37 °C for 30 minutes with anti-human CD73-FITC or anti-human CD90-FITC antibodies in DPBS at a 1:200 dilution. Following incubation, cells were washed three times with DPBS to remove unbound antibodies. The binding of antibodies to cells were subsequently analyzed using flow cytometry and confocal microscopy. To examine the cell spreading inhibition of BZP coating, MSC spheroids (5 × 103Attorney Docket No.11196-120WO1 cells per spheroid) were seeded on Geltrex™ LDEV-Free Reduced Growth Factor Basement Membrane Matrix coated 6-well plate and incubated in cell culture medium. After 3 days, cell spheroids were stained with 1 µM calcein-AM for 30 minutes at 37°C. The images were recorded using Olympus IX73 inverted microscope. To examine the protection against physical stress after encapsulation, MSC spheroids (5 × 103cells per spheroid) were subjected to vortexing (Vortex Mixer, Thermo Fisher Scientific) for 1 min. The resulting cells were imaged using Olympus IX73 inverted microscope. Immune protection. To assess the protection ability of BZP against immune cells, BZP- coated MCF7 spheroids (5 × 103cells per spheroid) were stained with CFSE (1 µM) for 1 h. NK- 92MI cells was washed twice with DPBS and labeled with CellTrace Far Red dye (1 µM) for 15 minutes at 37oC. Then, the cell spheroids were mixed with NK-92MI cells (2.5 × 104cells per well) in 96-well plate and incubated for 24 hours at 37oC with 5% CO2and relative humidity of 95%. Images were recorded using Olympus IX73 inverted microscope. To assess the protection ability of encapsulation method against cytokine attack, culture media supplemented with IL-1^ (5 ng / mL), TNF-^ (10 ng / mL), and IFN-^ (100 ng / mL) was prepared. The encapsulated islets were incubated with the proinflammatory cytokine supplemented culture media for 24 hours at 37oC with 5% CO2 and relative humidity of 95%. After the incubation, islets were dissociated by TrypLE Express Enzyme. Then, an apoptosis assay was performed using the Annexin V-FITC Apoptosis Detection Kit according to the manufacturer’s instructions. After the staining, cells were analyzed using flow cytometry. Cells in lower right quadrant were early apoptotic (Q3; annexin V positive, PI negative), cells in upper right quadrant were necrotic (Q2; annexin V positive, PI positive), and cells in lower left quadrant were viable (Q4; annexin V negative, PI negative). Cell populations in Q2 and Q3 were added for the comparison. Microparticle transplantation and intraperitoneal fluid analysis. Male BALB / c mice (5 weeks of age) used in this study were purchased from The Jackson Laboratory (Bar Harbor, ME). The microparticle solution with or without encapsulation (500 µL, 0.5% w / v) were intraperitoneally injected into the animals using 23G needle. At predetermined time points (day 1 or day 7), animals were euthanized by CO2 inhalation followed by cervical dislocation. A small incision was made on the abdomen skin for ice cold PBS (3 mL) injection. Next, a larger opening was created by using forceps and scissors along the skin of the abdomen and the peritoneal wall. The intraperitoneal fluid was carefully transferred into new 15 ml conical tubes using a pipette. The intraperitoneal fluid was examined by ELISA kits for the quantification of cytokine concentrations according to manufacturer’s instructions. Examination of islet activity. The glucose responsiveness of pancreatic islets was assessed through in vitro static glucose-stimulated insulin secretion (GSIS) assay. Islets wereAttorney Docket No.11196-120WO1 seeded in 24-well plate at a density of 200 IEQ per well, then exposed to 2.8 mM glucose (L) in Krebs Ringer Bicarbonate (KRB) buffer supplemented with 20 mM HEPES / Na-HEPES and 0.1% BSA for 30 minutes at 37oC for calibration prior to the study. Islets were sequentially exposed to 2.8 mM glucose (L1) for 1 hour, 16.7 mM glucose (H) for 1 hour, 2.8 mM glucose (L2) for 1 hour, and 2.8 mM glucose with 30 mM KCl (KCl) for 1 hour. For each step, solution was collected, and insulin amount was measured using ELISA kits. To assess the purity, islets were stained with saturated dithizone solution (50 µg / mL, in HBSS with 1% DMSO) for 5 minutes. Then, the islets were washed three times with fresh HBSS. The images were recorded using phase-contrast microscopy. To examine the cell viability after the encapsulation, islets were incubated in calcein AM (1 µM), ethidium homodimer-1 (1 µM), and Hoechst 33342 (1 µg / mL) added culture medium for 1 hour at 37oC. After the staining, the islets were washed twice with HBSS, and images were recorded using confocal scanning laser microscopy. Scanning electron microscopy of islets. Scanning electron microscopy (SEM) was employed to examine the surface morphology of the coated islets. Prior to imaging, the spheroids were carefully harvested and fixed in 2.5% glutaraldehyde at room temperature for 30 minutes to preserve cellular structures. Following fixation, the samples were washed with PBS and subjected to a graded ethanol series (25%, 50%, 70%, 85%, 95%, and 100%) for dehydration. The dehydrated islets were then critical point dried using carbon dioxide to prevent structural collapse. To enhance conductivity, the samples were sputter-coated with a thin layer of iridium using EM ACE600 (Leica, Wetzlar, Germany). SEM imaging was performed using Zeiss SIGMA VP-FESEM (SEM) at an accelerating voltage of 5 kV. Diabetic mice model. Diabetes in male BALB / c mice (age of 8–10 weeks; weight of 20- 25 g, Jackson Laboratory) was induced via multiple sequential administration of low dose streptozotocin. Briefly, streptozotocin solution was prepared in citrate buffer (pH 4.5). Each mouse was intraperitoneally injected for 5 consecutive days in a row at a dose of 50 mg / kg. The animal was considered to be diabetic if the blood glucose level readings were above the range of 200 – 250 mg / dl for 3 consecutive readings or once it reaches over 300 mg / dl. Blood glucose level was monitored once every three days using a Contour Next blood glucose monitor (Bayer, Leverkusen, Germany) with tail vein prick. Islet transplantation in peritoneal cavity. After the animals developed hyperglycemia (three consecutive blood glucose level readings above the range 200 – 250 mg / dl), rat pancreatic islets (Joslin Diabetes Center at Harvard Medical School, Boston, MA) were intraperitoneally injected using 23G needle. Each animal received islets in 500 µL serum-free media (1200 IEQs). Healthy mice did not receive any treatment. Diabetic mice received the same volume of DPBS with islet transplantation groups.Attorney Docket No.11196-120WO1 Islet transplantation in renal subcapsular space. Mouse islets (University of Pennsylvania, Philadelphia, PA) were placed into polyethylene tubes for transplantation. Recipient mice were anesthetized using isoflurane inhalation during the surgery. All mice subcutaneously received a 10 mL / kg dose of meloxicam as a pre-surgical analgesic. Following hair removal and disinfection, a small incision was made in the skin to expose the kidney. The subcapsular membrane of the kidney was carefully incised with a needle to allow the entry of the cell-containing tube. Polyethylene tube containing islets was inserted into the subcapsular membrane of the kidney using a syringe. Each animal received 700 IEQs of mouse islets in serum-free media. After the kidney was repositioned inside the body, peritoneum was sutured, and the skin was closed using wound clips. The mice were transferred to prewarmed cages for recovery and monitored. Intraperitoneal glucose tolerance test (IPGTT) and stimulated serum C-peptide. IPGTT was performed on postoperative day (POD) 20, POD 40, or POD 60. For the IPGTT, animals were fasted overnight and received an intraperitoneal glucose bolus (2 g / kg, in DPBS) after the fasting. Blood glucose levels were measured via tail vein prick before (0 min) and after administration at predetermined time points (15, 30, 45, 60, 90, and 120 min). Area under curve (AUC) was calculated and compared between the groups. For the stimulated serum C-peptide levels, blood samples were collected before glucose administration (0 min) and after glucose administration (30 min) via submental vein prick during the IPGTT. The serum C-peptide levels were analyzed using Rat C-Peptide ELISA kit or Mouse C-Peptide ELISA kit according to the manufacturer’s protocol. Statistical Analysis. Data were presented as means ± SD unless otherwise stated. GraphPad Prism software (GraphPad Software Inc.) was used to assess the statistical significance. Comparisons between two groups and the significance was assessed via one-way analysis of variance (ANOVA) with Dunnett’s multiple comparisons test. Comparisons between multiple groups were analyzed via ANOVA followed by Tukey’s post hoc test. Comparisons between two profiles were analyzed via Mantel-Cox log-rank test. The data was considered to be statistically significant when p-value was less than 0.05 (P < 0.05).

[0160] All publications, patents, and patent applications, Genbank sequences, websites and other published materials referred to throughout the disclosure herein are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application, Genbank sequences, websites and other published materials was specifically and individually indicated to be incorporated by reference. In the event that the definition of a term incorporated by reference conflicts with a term defined herein, this specification shall control.Attorney Docket No.11196-120WO1 REFERENCES Alagpulinsa, D. A. et al. Alginate-microencapsulation of human stem cell–derived ^ cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression. American Journal of Transplantation 19, 1930–1940 (2019). Bashor, C. J., Hilton, I. B., Bandukwala, H., Smith, D. M. & Veiseh, O. Engineering the next generation of cell-based therapeutics. 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Advanced Materials 32, (2020). Desai, T. & Shea, L. D. Advances in islet encapsulation technologies. Nat Rev Drug Discov 16, 338–350 (2017). Doloff, J. C. et al. Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates. Nat Mater 16, 671–680 (2017). Dunn, M. R., Jimenez, R. M. & Chaput, J. C. Analysis of aptamer discovery and technology. Nat Rev Chem 1, 1–16 (2017). Ellington, A. D. & Szostak, J. W. In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818–822 (1990). Engberg, K. & Frank, C. W. Protein diffusion in photopolymerized poly(ethylene glycol) hydrogel networks. Biomed. Mater.6, (2011).Attorney Docket No.11196-120WO1 Farina, M., Alexander, J. F., Thekkedath, U., Ferrari, M. & Grattoni, A. Cell encapsulation: Overcoming barriers in cell transplantation in diabetes and beyond. Adv Drug Deliv Rev 139, 92–115 (2019). Fukuda, Y. et al. Layer-by-layer cell coating technique using extracellular matrix facilitates rapid fabrication and function of pancreatic ^-cell spheroids. Biomaterials 160, 82–91 (2018). Gardner, T. S., Cantor, C. R. & Collins, J. J. Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339–342 (2000). Haque, M. R. et al. Xenotransplantation of layer-by-layer encapsulated non-human primate islets with a specified immunosuppressive drug protocol. Journal of Controlled Release 258, 10–21 (2017). Khalil, A. S. & Collins, J. J. Synthetic biology: applications come of age. Nat. Rev. Genet. 11, 367–379 (2010). Kim, M. et al. Novel enzymatic cross-linking-based hydrogel nanofilm caging system on pancreatic ^ cell spheroid for long-term blood glucose regulation. Sci Adv 7, 7832–7855 (2021). Li, B. et al. De novo design of functional zwitterionic biomimetic material for immunomodulation. Sci Adv 6, (2020). Li, Q. et al. Zwitterionic Biomaterials. Chem Rev 122, 17073–17154 (2022). Lim, F. & Sun, A. M. Microencapsulated islets as bioartificial endocrine pancreas. Science 210, 908–910 (1980). Litscher, E. S. & Wassarman, P. M. Zona Pellucida Proteins, Fibrils, and Matrix. Annu Rev Biochem 89, 695–715 (2020). Liu, Q. et al. Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation. Nat Commun 10, (2019). Liu, S. S. et al. Encapsulated islet transplantation. Nature Reviews Bioengineering 1–20 (2024). Mao, A. S. et al. Deterministic encapsulation of single cells in thin tunable microgels for niche modelling and therapeutic delivery. Nat Mater 16, 236–243 (2017). Michael B. Elowitz & Stanislas Leibler. A synthetic oscillatory network of transcriptional regulators. Nature 403, 335–338 (2000). Mitrousis, N., Fokina, A. & Shoichet, M. S. Biomaterials for cell transplantation. Nat Rev Mater 3, 441–456 (2018). Mosesson, M. W. Fibrinogen and fibrin structure and functions. Journal of Thrombosis and Haemostasis 3, 1894–1904 (2005).Attorney Docket No.11196-120WO1 Nombela-Arrieta, C., Ritz, J. & Silberstein, L. E. The elusive nature and function of mesenchymal stem cells. Nat Rev Mol Cell Biol 12, 126–131 (2011). Orive, G. et al. Cell encapsulation: technical and clinical advances. Trends Pharmacol Sci 36, 537–546 (2015). Pinheiro, V. B. et al. Synthetic Genetic Polymers Capable of Heredity and Evolution. Purnick, P. E. M. & Weiss, R. The second wave of synthetic biology: from modules to systems. Nat. Rev. Mol. Cell Biol. 10, 410–422 (2009). Science (80-. ). 336, 341–344 (2012). Shao, Q. & Jiang, S. Molecular understanding and design of zwitterionic materials. Advanced Materials 27, 15–26 (2015). Shi, P., Zhao, N., Coyne, J. & Wang, Y. DNA-templated synthesis of biomimetic cell wall for nanoencapsulation and protection of mammalian cells. Nat Commun 10, 2223 (2019). Singh, N. K. et al. High-affinity one-step aptamer selection using a non-fouling porous hydrogel. Nat Biotechnol 42, 1224–1231 (2023). Szostak, J. W., Bartel, D. P. & Luisi, P. L. Synthesizing life. Nature 409, 387–390 (2001). Tang, T. C. et al. Materials design by synthetic biology. Nature Reviews Materials vol.6 332–350 (2021). Tran, P. Le et al. Prolongation of graft survival via layer-by-layer assembly of collagen and immunosuppressive particles on pancreatic islets. Biomaterials 290, (2022). Tuerk, C. & Gold, L. Systematic Evolution of Ligands by Exponential Enrichment: RNA Ligands to Bacteriophage T4 DNA Polymerase. Science 249, 505–510 (1990). Vegas, A. J. et al. Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat Med 22, 306–311 (2016). Veiseh, O. & Vegas, A. J. Domesticating the foreign body response: Recent advances and applications. Adv Drug Deliv Rev 144, 148–161 (2019). Veiseh, O. et al. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat Mater 14, 643–651 (2015). Wang, H. & Mooney, D. J. Biomaterial-assisted targeted modulation of immune cells in cancer treatment. Nat Mater 17, 761–772 (2018). Wang, L. H. et al. Inflammation-induced subcutaneous neovascularization for the long- term survival of encapsulated islets without immunosuppression. Nat Biomed Eng 8, 1– 19 (2023). Wassarman, P. et al. Structure and function of the proteins of the mammalian zona pellucida. Journal of Experimental Zoology 285, 251–258 (1999).Attorney Docket No.11196-120WO1 Wassarman, P. M. Zona pellucida glycoproteins. Journal of Biological Chemistry 283, 24285–24289 (2008). Wilson, J. T., Cui, W. & Chaikof, E. L. Layer-by-layer assembly of a conformal nanothin PEG coating for intraportal islet transplantation. Nano Lett 8, 1940–1948 (2008). Zhang, L. et al. Zwitterionic hydrogels implanted in mice resist the foreign-body reaction. Nat Biotechnol 31, 553–556 (2013). Zhao, S. et al. Bioengineering of injectable encapsulated aggregates of pluripotent stem cells for therapy of myocardial infarction. Nat Commun 7, (2016).Attorney Docket No.11196-120WO1 TABLES Table 1. DNA sequences used for thrombin immobilization and characterization.

Claims

Attorney Docket No.11196-120WO1 CLAIMS What is claimed is:

1. A microparticle, cell, or therapeutic agent coated with biomimetic zona pellucida (BZP), wherein the microparticle, cell, or therapeutic agent comprises a functionalized surface; and wherein the BZP comprises a 3D polymer meshwork bound to a functionalized surface of the microparticle.

2. The microparticle, cell, or therapeutic agent of claim 1, wherein the microparticle comprises a biocompatible material.

3. The microparticle, cell, or therapeutic agent of claim 2, wherein the biocompatible material is selected from polystyrene, poly(lactic-co-glycolic acid) (PLGA), silica, and agarose.

4. The microparticle, cell, or therapeutic agent of any one of claims 1-3, wherein the microparticle or cell is 10-100 ^m in diameter.

5. The microparticle, cell, or therapeutic agent of any one of claims 1-4, wherein the functionalized surface of the microparticle comprises an enzyme-binding molecule and an enzyme.

6. The microparticle, cell, or therapeutic agent of claim 5, wherein the enzyme-binding molecule is an aptamer that binds the enzyme.

7. The microparticle, cell, or therapeutic agent of any one of claims 5-6, wherein the enzyme-binding molecule is an anti-thrombin aptamer comprising a sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO:

3.

8. The microparticle, cell, or therapeutic agent of claim 7, wherein the anti-thrombin aptamer comprises SEQ ID NO:

2.

9. The microparticle, cell, or therapeutic agent of any one of claims 5-8, wherein the enzyme-binding molecule is streptavidin.

10. The microparticle, cell, or therapeutic agent of any one of claims 5-9, wherein the enzyme-binding molecule is a biotinylated DNA aptamer.Attorney Docket No.11196-120WO1 11. The microparticle, cell, or therapeutic agent of any one of claims 5-10, wherein the enzyme is selected from thrombin, tyrosinase, transglutaminase, peroxidase, sortase, horseradish peroxidase, and alkaline phosphatase.

12. The microparticle, cell, or therapeutic agent of any one of claims 5-11, wherein the enzyme is a serine protease enzyme.

13. The microparticle, cell, or therapeutic agent of claim 12, wherein the serine protease enzyme is thrombin.

14. The microparticle, cell, or therapeutic agent of any one of claims 5-13, wherein the enzyme is provided to the microparticle, cell, or therapeutic agent at between about 0.1 U / mL and about 10 U / mL.

15. The microparticle, cell, or therapeutic agent of any one of claims 5-14, wherein the enzyme is provided to the microparticle, cell, or therapeutic agent at about 1 U / ml.

16. The microparticle, cell, or therapeutic agent of any one of claims 1-15, wherein the BZP is 10 to 30 µm in thickness.

17. The microparticle, cell, or therapeutic agent of any one of claims 1-16, wherein the 3D polymer meshwork comprises a polymer coating crosslinked with one or more blending molecules, comprised in a blending solution.

18. The microparticle, cell, or therapeutic agent of claim 17, wherein the polymer coating comprises a coating molecule.

19. The microparticle, cell, or therapeutic agent of any one of claims 5-18, wherein the enzyme cleaves a coating molecule and assembles the polymer coating.

20. The microparticle, cell, or therapeutic agent of any one of claims 18-19, wherein the coating molecule comprises fibrinogen conjugated to dibenzocyclooctyne (DBCO) (fibrinogen-DBCO).

21. The microparticle, cell, or therapeutic agent of any one of claims 17-20, wherein the polymer coating is fibrin.

22. The microparticle, cell, or therapeutic agent of any one of claims 17-21, wherein the oneAttorney Docket No.11196-120WO1 or more blending molecules comprise an alginate.

23. The microparticle, cell, or therapeutic agent of any one of claims 17-22, wherein the blending solution comprises alginate-azide.

24. The microparticle, cell, or therapeutic agent of any one of claims 17-23, wherein the blending solution comprises a mixture of sodium alginate solution (0.125% w / v) and alginate-azide solution (0.125% w / v).

25. The microparticle, cell, or therapeutic agent of any one of claims 17-24, wherein the blending solution is between about 0.05% w / g and about 5% w / v.

26. The microparticle, cell, or therapeutic agent of any one of claims 17-25, wherein the blending solution is about 0.25% w / v.

27. The microparticle, cell, or therapeutic agent of any one of claims 18-26, wherein the coating molecule or the one or more blending molecule is conjugated to dibenzocyclooctyne (DBCO), while the other, the coating molecule or the one or more blending molecule, is conjugated to azide.

28. The microparticle, cell, or therapeutic agent of any one of claims 18-27, wherein the coating molecule is provided to the microparticle, cell, or therapeutic agent at between about 1 mg / mL and about 20 mg / mL.

29. The microparticle, cell, or therapeutic agent of any one of claims 18-28, wherein the coating molecule is provided to the microparticle, cell, or therapeutic agent at about 10 mg / mL.

30. The microparticle, cell, or therapeutic agent of any one of claims 17-29, wherein the polymer coating is further crosslinked with one or more blending molecules, by a fortifying solution, to form a hardened BZP.

31. The microparticle, cell, or therapeutic agent of claim 30, wherein the fortifying solution comprises polylysine and calcium chloride.

32. The microparticle, cell, or therapeutic agent of any one of claims 30-31, wherein the fortifying solution comprises 0.05% w / v of polylysine and 50 mM calcium chlorideAttorney Docket No.11196-120WO1 solution.

33. The microparticle, cell, or therapeutic agent of any one of claims 1-32, wherein the cell is selected from mesenchymal stem cell, human neural stem cell, pancreatic islet, articular chondrocyte, fibroblast, red blood cell, platelet, cancer cell, and microbial cell.

34. The microparticle, cell, or therapeutic agent of claim 33, wherein the microbial cell is a bacteria, fungi or yeast.

35. The microparticle, cell, or therapeutic agent of any one of claims 1-34, wherein the cell is a pancreatic islet cell.

36. The microparticle, cell, or therapeutic agent of any one of claims 1-35, wherein the therapeutic agent is a drug or a biologically active compound.

37. A method for coating a microparticle, cell, or therapeutic agent with a biomimetic zona pellucida (BZP), the method comprising, (a) incubating the microparticle, cell, or therapeutic agent with an enzyme- binding molecule conjugated to a cell membrane insertion moiety; (b) incubating the microparticle, cell, or therapeutic agent with an enzyme that binds the enzyme-binding molecule; (c) incubating the microparticle, cell, or therapeutic agent with a coating solution comprising a coating molecule that binds the enzyme to form a polymer coating on the surface of the microparticle, cell, or therapeutic agent; (d) incubating the microparticle, cell, or therapeutic agent with a blending solution comprising one or more blending molecules that crosslink with the polymer coating to form a hydrogel layer on the surface of the microparticle, cell, or therapeutic agent; (e) incubating the cell with a fortifying solution that hardens the BZP when reacted with at least one of the hydrogel and the polymer coating; and (f) incubating the cell with the blending solution.

38. The method of claim 37, further comprising at least one of: washing the microparticle, cell, or therapeutic agent before step (a); washing the microparticle, cell, or therapeutic agent between steps (a) and (b); washing the microparticle, cell, or therapeutic agent between steps (b) and (c);Attorney Docket No.11196-120WO1 washing the microparticle, cell, or therapeutic agent between steps (c) and (d); washing the microparticle, cell, or therapeutic agent between steps (e) and (f); and washing the microparticle, cell, or therapeutic agent after step (f).

39. The method of any one of claims 37-38, wherein the BZP is 10 to 30 µm in thickness.

40. The method of any one of claims 37-39, wherein the method is performed at between about 0°C and about 37°C.

41. The method of any one of claims 37-40, wherein the method is performed at room temperature.

42. The method of any one of claims 37-41, wherein the enzyme-binding molecule is an aptamer that binds the enzyme.

43. The method of any one of claims 37-42, wherein the enzyme-binding molecule is an anti- thrombin aptamer comprising a sequence selected from SEQ ID NO: 1-3.

44. The method of claim 43, wherein the anti-thrombin aptamer comprises SEQ ID NO:

2.

45. The method of any one of claims 37-44, wherein the enzyme-binding molecule is streptavidin.

46. The method of any one of claims 37-45, wherein the enzyme-binding molecule is a biotinylated DNA aptamer.

47. The method of any one of claims 37-46, wherein the cell membrane insertion moiety is selected from cholesterol, a diacyl lipid, tocopherol, a ceramide, sphingomyelin, a phosphatidylcholine, a phosphatidylethanolamine, a phosphatidylserine, a glycolipid, and a fatty acid.

48. The method of any one of claims 37-47, wherein the cell membrane insertion moiety comprises cholesterol.

49. The method of any one of claims 37-48, wherein the enzyme is selected from thrombin, tyrosinase, transglutaminase, peroxidase, sortase, horseradish peroxidase, and alkalineAttorney Docket No.11196-120WO1 phosphatase.

50. The method of any one of claims 37-49, wherein the enzyme is a serine protease enzyme.

51. The method of claim 50, wherein the serine protease enzyme is thrombin.

52. The method of any one of claims 37-51, wherein in step (b) the enzyme is provided to the microparticle, cell, or therapeutic agent at between about 0.1 U / mL and about 10 U / mL.

53. The method of any one of claims 37-52, wherein in step (b), the enzyme is provided to the microparticle, cell, or therapeutic agent at about 1 U / ml.

54. The method of any one of claims 37-53, wherein the coating molecule comprises fibrinogen; and wherein the polymer coating is fibrin.

55. The method of any one of claims 37-54, wherein the blending solution wherein the one or more blending molecules comprise an alginate.

56. The method of any one of claims 37-55, wherein the blending solution comprises a mixture of sodium alginate solution (0.125% w / v) and alginate-azide solution (0.125% w / v).

57. The method of any one of claims 37-56, wherein the blending solution is between about 0.05% w / g and about 5% w / v.

58. The method of any one of claims 37-57, wherein the blending solution is about 0.25% w / v.

59. The method of any one of claims 37-58, wherein the coating molecule comprises fibrinogen conjugated to dibenzocyclooctyne (DBCO) (fibrinogen-DBCO); and wherein the blending solution further comprises alginate-azide.

60. The method of any one of claims 37-59, wherein the coating molecule or the one or more blending molecule is conjugated to dibenzocyclooctyne (DBCO), while the other, the coating molecule or the one or more blending molecule, is conjugated to azide.Attorney Docket No.11196-120WO1 61. The method of any one of claims 37-60, wherein the coating molecule is provided to the microparticle, cell, or therapeutic agent at between about 1 mg / mL and about 20 mg / mL.

62. The method of any one of claims 37-61, wherein the coating molecule is provided to the microparticle, cell, or therapeutic agent at about 10 mg / mL.

63. The method of any one of claims 37-62, wherein the fortifying solution comprises polylysine and calcium chloride.

64. The method of any one of claims 37-63, wherein the fortifying solution comprises 0.05% w / v of polylysine and 50 mM calcium chloride solution.

65. The method of any one of claims 37-64, wherein the cell is selected from mesenchymal stem cell, human neural stem cell, pancreatic islet, articular chondrocyte, fibroblast, red blood cell, platelet, cancer cell, and microbial cell.

66. The method of claim 65, wherein the microbial cell is a bacteria, fungi or yeast.

67. The method of any one of claims 37-66, wherein the cell is a pancreatic islet cell.

68. A method for reducing a blood glucose level and / or treating diabetes in a subject in need thereof, the method comprising administering to the subject the microparticle, cell, or therapeutic agent of claims 1-36.

69. A method of treating diabetes in a subject, comprising administering to the subject a pancreatic islet cell coated with a biomimetic zona pellucida (BZP), wherein the pancreatic islet cell comprises a functionalized surface; wherein the BZP comprises a 3D polymer meshwork bound to a functionalized surface of the pancreatic islet cell; wherein the pancreatic islet cell coated with BZP exhibits a reduced degree of susceptibility to proinflammatory cytokines, and decreased blood glucose levels in a treated subject compared to a control; and wherein the decreased blood glucose levels indicates an effective treatment of diabetes.

70. The method of claim 69, wherein the functionalized surface of the pancreatic islet cell comprises an enzyme-binding molecule conjugated to a cell membrane insertion moiety and an enzyme.Attorney Docket No.11196-120WO1 71. The method of claim 70, wherein the enzyme-binding molecule is an aptamer that binds the enzyme.

72. The method of any one of claims 70-71, wherein the enzyme-binding molecule is an anti- thrombin aptamer comprising a sequence selected from SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO:

3.

73. The method of claim 72, wherein the anti-thrombin aptamer comprises SEQ ID NO:

2.

74. The method of any one of claims 70-73, wherein the enzyme-binding molecule is streptavidin.

75. The method of any one of claims 70-74, wherein the enzyme-binding molecule is a biotinylated DNA aptamer.

76. The method of any one of claims 70-75, wherein the cell membrane insertion moiety is selected from cholesterol, a diacyl lipid, tocopherol, a ceramide, sphingomyelin, a phosphatidylcholine, a phosphatidylethanolamine, a phosphatidylserine, a glycolipid, and a fatty acid.

77. The method of any one of claims 70-76, wherein the cell membrane insertion moiety comprises cholesterol.

78. The method of any one of claimswherein the enzyme is selected from thrombin, tyrosinase, transglutaminase, peroxidase, sortase, horseradish peroxidase, and alkaline phosphatase.

79. The method of any one of claims 70-78, wherein the enzyme is a serine protease enzyme.

80. The method of claim 79, wherein the serine protease enzyme is thrombin.

81. The method of any one of claims 70-80, wherein the enzyme is provided to the pancreatic islet cell at between about 0.1 U / mL and about 10 U / mL.

82. The method of any one of claims 70-81, wherein the enzyme is provided to the pancreatic islet cell at about 1 U / ml.Attorney Docket No.11196-120WO1 83. The method of any one of claims 69-82, wherein the BZP is 10 to 30 µm in thickness.

84. The method of any one of claims 69-83, wherein the 3D polymer meshwork comprises a polymer coating crosslinked with one or more blending molecules, comprised in a blending solution.

85. The method of claim 84, wherein the polymer coating comprises a coating molecule.

86. The method of any one of claims 70-85, wherein the enzyme cleaves a coating molecule and assembles the polymer coating.

87. The method of any one of claims 85-86, wherein the coating molecule comprises fibrinogen conjugated to dibenzocyclooctyne (DBCO) (fibrinogen-DBCO).

88. The method of any one of claims 84-87, wherein the polymer coating is fibrin.

89. The method of any one of claims 84-88, wherein the one or more blending molecules comprise an alginate.

90. The method of any one of claims 84-89, wherein the blending solution comprises alginate-azide.

91. The method of any one of claims 84-90, wherein the blending solution comprises a mixture of sodium alginate solution (0.125% w / v) and alginate-azide solution (0.125% w / v).

92. The method of any one of claims 84-91, wherein the blending solution is between about 0.05% w / g and about 5% w / v.

93. The method of any one of claims 84-92, wherein the blending solution is about 0.25% 94. The method of any one of claims 85-93, wherein the coating molecule or the one or more blending molecule is conjugated to dibenzocyclooctyne (DBCO), while the other, the coating molecule or the one or more blending molecule, is conjugated to azide.

95. The method of any one of claims 85-94, wherein the coating molecule is provided to the pancreatic islet cell at between about 1 mg / mL and about 20 mg / mL.Attorney Docket No.11196-120WO1 96. The method of any one of claims 85-95, wherein the coating molecule is provided to the pancreatic islet cell at about 10 mg / mL.

97. The method of any one of claims 84-96, wherein the polymer coating is further crosslinked with one or more blending molecules, by a fortifying solution, to form a hardened BZP.

98. The method of claim 97, wherein the fortifying solution comprises polylysine and calcium chloride.

99. The method of any one of claims 97-98, wherein the fortifying solution comprises 0.05% w / v of polylysine and 50 mM calcium chloride solution.

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