Biocompatible polymer compositions and methods of use

Abstract

Provided herein are compositions comprising microgels conjugated to a protease-resistant C-X-C motif chemokine 12 (CXCL12) polypeptide, a Fas ligand (FasL) polypeptide, or both. Methods of making the microgel compositions as well as pharmaceutical compositions comprising thereof are also contemplated herein. Provided herein are also methods of inducing an immune privileged environment for transplantation, methods of treating or preventing graft rejection in a subject in need thereof, as well as methods of treating Type 1 diabetes.

Description

[0001]BIOCOMPATIBLE POLYMER COMPOSITIONS AND METHODS OF USE CLAIM OF PRIORITY This application claims the benefit of U.S. Provisional Application Serial Nos. 63 / 656,652, filed on June 6, 2024, and 63 / 688,366, filed on August 29, 2024. The entire contents of the foregoing are incorporated herein by reference. SEQUENCE LISTING This application contains a Sequence Listing that has been submitted electronically as an XML file named 29539-0834WO1_SL_ST26.xml. The XML file, created on June 4, 2025, is 42,563 bytes in size. The material in the XML file is hereby incorporated by reference in its entirety. TECHNICAL FIELD Provided herein are compositions comprising microgels conjugated to a protease-resistant C-X-C motif chemokine 12 (CXCL12) polypeptide, a Fas ligand (FasL) polypeptide, or both. Methods of making the microgel compositions as well as pharmaceutical compositions comprising thereof are also contemplated herein. Provided herein are also methods of inducing an immune privileged environment for transplantation, methods of treating or preventing graft rejection in a subject in need thereof, as well as methods of treating Type 1 diabetes. BACKGROUND Yearly, over 40,000 organ transplants are performed in the United States alone. The transplantation field in general faces critical challenges, such as the need for lifelong systemic immunosuppression in organ transplant recipients (see, e.g., Piao et al., J Biomed Opt.2018 Aug;23(8):1-14; Lepoittevin et al., Int J Mol Sci.2022 Apr 30;23(9):4989; Henkel et al., Front Transplant.2023 Aug 21;2:1160752). For example, an emerging treatment for Type 1 Diabetes (T1D) is allo-islet transplantation; however, the need for lifelong immunosuppression to protect the transplanted cells from allo- and autoimmune-mediated rejection, coupled with the scarcity of donor islets, poses significant barriers. Immunosuppressive therapy also increases the risk of infections, organ damage, and cancer3,4, complicating the balance between treatment benefits and risks. SUMMARY Provided herewith are compositions and methods of using thereof to induce an immune privileged environment for transplanted organs, tissues, and / or cells. Immune privilege is a complex process that protects organs from immune-mediated attack and damage, e.g., provides immunoprotection for the for transplanted organs, tissues, and / or cells. Disclosed herein are microgels displaying the protease resistant chemokine, CXCL12 (prCXCL12), and Fas Ligand (FasL) to facilitate transplantation (e.g., allo-islet transplantation) without systemic immunosuppression. Provided herein is an embodiment of this localized combinatorial strategy that utilized microgels displaying both fusion proteins of streptavidin and protease-resistant CXCL12 (SA- prCXCL12) and streptavidin and Fas ligand (SA-FasL) to enable functional, long- term allo-islet transplantation in a murine model of type 1 diabetes (T1D) without the need for systemic immunosuppression. This strategy enhances immunoprotection, enabling the transplantation of organs, tissues, and / or cells (e.g., allogeneic islets) without systemic immune suppression or micro / macroencapsulation11. The methods provided herein utilize locally immunosuppressive activities of SA-FasL and SA-prCXCL12 displayed by a microgel when implanted locally together with the graft (e.g., islet graft). This therapeutic approach can potentially induce synergistic, broad immunoisolation by both repelling and inducing the death of effector T cells while increasing the number and function of Tregs near the islet graft46,47,54. The use of prCXCL12 addresses the limited active half-llpife of wild-type CXCL12 due to proteolytic degradation, enhancing the duration of its immuno modulatory effects, pro-survival signaling within the graft (e.g., islet graft) and its ability to enhance graft vascularization. The methods herein of using a combined microgel and allo-islet approach could eliminate the need for systemic immunosuppression to enable long-term function of transplanted islets. Thus, disclosed herein is a composition comprising a plurality of biotinylatedmicrogels, wherein the plurality of biotinylated microgels comprises at least one biotinylated microgel comprising: at least one fusion protein comprising a protease- resistant C-X-C motif chemokine 12 (CXCL12) polypeptide fused to a first streptavidin moiety or first avidin moiety; and at least one fusion protein comprising a Fas ligand (FasL) polypeptide fused to a second streptavidin moiety or second avidin moiety. In some instances, the protease-resistant CXCL12 polypeptide comprises an amino acid sequence at least 70% identical to SEQ ID NO: 2. In some instances, the FasL ligand polypeptide comprises an amino acid sequence at least 70% identical to SEQ ID NO: 15. In some instances, the composition comprises between 1% and 80% (w / w) of biotinylated microgels conjugated to the at least one fusion protein comprising the protease-resistant CXCL12 polypeptide fused to the first streptavidin moiety or the first avidin moiety. In some instances, the composition comprises about 50% (w / w) of biotinylated microgels conjugated to the at least one fusion protein comprising the protease-resistant CXCL12 polypeptide fused to the first streptavidin or the first avidin moiety. In some instances, the composition comprises between 1% and 80% (w / w) of biotinylated microgels conjugated to at least one fusion protein (prCXCL12) and a second immune-modulatory or immune regulatory or anti-inflammatory polypeptide fused to the second streptavidin moiety or the second avidin moiety. In some instances, the composition comprises about 50% (w / w) of biotinylated microgels conjugated to at least one fusion protein comprising a second immune-modulatory or immune regulatory or anti-inflammatory protein to the second streptavidin moiety or the second avidin moiety. In some instances, the first and / or second streptavidin or the first and / or second avidin moiety comprises an amino acid sequence at least 80% identical to SEQ ID NOs: 5-8. In some instances, the biotinylated microgel comprises a diameter ranging from 150 to about 200 microns. Also disclosed herein is a composition comprising a plurality of biocompatible polymers, wherein the plurality of biocompatible polymer comprises at least one biocompatible polymer comprising: at least one fusion protein comprising a protease- resistant C-X-C motif chemokine 12 (CXCL12) polypeptide fused to a firststreptavidin moiety or first avidin moiety; and at least one fusion protein comprisinga Fas ligand (FasL) polypeptide fused to a second streptavidin moiety or second avidin moiety. In some instances, the composition further comprises at least one polyethylene glycol (PEG) macromer. In some instances, the PEG macromer is selected from the group consisting of a PEG-maleimide (PEG-MAL) macromer, a PEG-acrylate (PEG-Ac) macromer, a PEG-vinylsulfone (PEG-VS) macromer, and a PEG-diacrylate (PEG-DA) macromer. In some instances, the PEG macromer comprises a multi-arm PEG macromer, wherein a functional group is attached to the terminal end of the arm. In some instances, the multi-arm PEG macromer comprises at least four arms. In some instances, the biotinylated microgels disclosed herein further include at least one biomaterial selected from the group consisting of methacrylated hyaluronic acid (HAMA), poly(lactic-co-glycolic acid) (PLGA), alginate, gelatin, and gelatin methacrylate (GelMA). In some instances, the composition further comprises at least one polyethylene glycol (PEG) macromer. In some instances, the PEG macromer is selected from the group consisting of a PEG-maleimide (PEG-MAL) macromer, a PEG-acrylate (PEG-Ac) macromer, a PEG-vinylsulfone (PEG-VS) macromer, and a PEG-diacrylate (PEG-DA) macromer. In some instances, the PEG macromer comprises a multi-arm PEG macromer, wherein a functional group is attached to the terminal end of the arm. In some instances, the multi-arm PEG macromer comprises at least four arms. In some instances, the composition comprises at least one biomaterial selected from the group consisting of methacrylated hyaluronic acid (HAMA), poly(lactic-co-glycolic acid) (PLGA), alginate, gelatin, and gelatin methacrylate (GelMA). In some instances, the composition is configured to release at least 50% of the amount of the protease-resistant CXCL12 polypeptide and / or the FasL polypeptide over 2 to 60 days after a transplantation. In some instances, the composition is biodegradable. Also disclosed are methods of treating or preventing graft rejection in a subject in need thereof, the method comprising administering an effective amount of any one of the compositions in this disclosure to the subject in need thereof, wherein the administering occurs before transplantation of a graft, at the time oftransplantation the graft, after transplantation of the graft, or any combination thereof.In some instances, disclosed are methods of inducing an immune privileged environment in a subject in need thereof, the method comprising implanting an effective amount of any one of the compositions in this disclosure in a subject in need thereof, wherein the implantation is localized to a site of graft transplantation. In some instances, disclosed are methods of inducing a graft vascularization in a subject in need thereof, the method comprising implanting an effective amount of any one of the compositions in this disclosure in a subject in need thereof, wherein the implantation is localized to a site of graft transplantation. In some instances, the implanting occurs before transplantation of the graft, at the time of transplanting the graft, after transplantation of the graft, or any combination thereof. In some instances, the composition and the graft are co- implanted. In some instances, the subject in need thereof does not require immunosuppressive therapy after transplantation of the graft. In some instances, the subject does not require immunosuppressive treatment for at least 60 days after transplantation of the graft. In some instances, the graft is an allograft. In some instances, the subject in need thereof is a transplant recipient or is at risk of needing a transplant. In some instances the subject is a recipient of or is at risk of needing transplantation of at least one cell, at least one tissue, at least one organ, or any combination thereof. In some instances, the transplant is an islet cell transplant, a pancreas transplant, a skin graft, a skin transplant, a bone graft, a bone marrow graft, a bone marrow transplant, a heart transplant, a kidney transplant, a lung transplant, a liver transplant, a vascular-composite allograft, or any combination thereof. Also disclosed is a method of treating Type 1 Diabetes (T1D) in a subject in need thereof, the method comprising administering an effective amount of the composition of any one of claims 1-16 to the subject in need thereof, wherein the administering occurs before islet allotransplantation, at the time of islet allotransplantation, after islet allotransplantation, or any combination thereof. In some instances, the effective amount of the composition and the islet allograft are co-transplanted, wherein the site of co-transplantation is an extrahepatic site. In some instances, the site of co-transplantation is in the omentum of the subjectin need thereof. In some instances, the subject in need thereof does not requireimmunosuppressive treatment after islet allotransplantation. In some instances, the subject in need thereof is normoglycemic for at least 60 days after islet allotransplantation. In some instances, the islet allograft survives at least 60 days after islet allotransplantation. In some instances, the subject in need thereof is normoglycemic after islet allotransplantation. In some instances, the subject in need thereof does not require immunosuppressive treatment for about 1 week to 6 months after islet allotransplantation. In some instances, the subject in need thereof is a human. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Methods and materials are described herein for use in the present invention; other, suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. As used herein, the term “about” means plus or minus 10%. In the present disclosure, the percentage of “sequence identity” between two sequences can be determined by comparing two such sequences over their entire length by global pairwise alignment using the algorithm of Needleman and Wunsch (J. Mol. Biol. 48:443 (1970)), e.g., using the program Needle (EMBOSS) with the BLOSUM62 matrix and the following parameters: gap open=10, gap extend=0.5, end gap penalty=false, end gap open=10, end gap extend=0.5 (which are standard settings). Other features and advantages of the invention will be apparent from the following detailed description and figures, and from the claims. DESCRIPTION OF DRAWINGS FIGS.1A and 1B depict streptavidin CXCL12 (SA-CXCL12) and streptavidin protease-resistant CXCL12 (SA-prCXCL12) protein production and validation with Western blot analysis. Stably transfected cells were induced for protein expression for 2 or 3 days. Protein was purified using Ni-affinity columns. FIG.1A: As shown inthis representative gel, SA-CXCL12 and SA-prCXCL12 proteins were characterizedfor purity and structure using Western blots (2nd well heat treated and 3rd well unheated) 100 ng SA-CXCL12 (left), and 100 ng SA-prCXCL12 (right). FIG.1B: As shown in this representative gel, different SA-CXCL12 and SA concentrations were loaded into wells for SA-CXCL12 antibody verification. H = heat treated (100°C x 10 min), RT = room temperature (22°C ± 3°C). FIGS.2A and 2B depict binding and release of SA-CXCL12 from microgels. FIG.2A: 1,000 microgels were mixed with 500 μl PBS + 1 μg SA-CXCL12, incubated at RT for 2 hours, then centrifuged. Resulting supernatants were run on a Western Blot. After the engineering of protein with microgel, an average of 14.7% SA-CXCL12 remained in the supernatant (A1, B1, B2) and 85.3% of SA-CXCL12 was bound by microgels. FIG.2B: In vitro release of CXCL12 without SA from the microgel was measured over a 48-hour period using tagged anti-CXCL12 with DyLight 488 (n=3). FIGS.3A and 3B depict the release of SA-CXCL12 (FIG.3A) and SA- prCXCL12 (FIG.3B) from microgels. A total of 1,000 microgels were incubated in 500 μL of PBS containing 1 μg of SA-CXCL12 or SA-prCXCL12 at room temperature for 2 hours. After incubation, microgels were centrifuged to separate the unbound SA-prCXCL12 in the supernatant. The in vitro release profile of SA- prCXCL12 from the microgels was subsequently measured over a 72-hour period (n=3). FIGS.4A-4I depict SA-CXCL12 (FIGS.4A-4D) and SA-prCXCL12 (FIGS. 4E–4H) exhibited dose-dependent chemotactic or chemorepellent activity (fugetaxis) on splenocytes and primary CD3+T cells isolated from human PBMC in vitro (n=3). SA-prCXCL12 induced a stronger fugetactic response than SA-CXCL12 in both splenocytes and CD3⁺ T cells. In the chemotaxis assay, CXCL12 protein was added to the lower chamber of a transwell system to attract T cells, allowing them to migrate toward the CXCL12 gradient. In contrast, for the fugetaxis assay, CXCL12 was added to the upper chamber, creating a gradient that repelled T cells from the upper chamber to the lower chamber. To mitigate the chemotactic effects of the chemokine, cells in the top chamber were treated with AMD3100 (200 nM) for 30 minutes at 37°C, while the lower chamber contained active recombinant protein CXCL12 (positive control),SA-CXCL12 (FIGS. 4A, 4B) or SA-prCXCL12 (FIGS. 4E, 4F). To mitigatefugetaxis, T cells in the top chamber were treated with AMD3100 (200 nM) for 30 minutes, then cells were resuspended in recombinant protein CXCL12 (positive control), SA-CXCL12 (FIGS.4C, 4D) or SA-prCXCL12 (FIGS.4G, 4H). Plates were incubated for 3 hours at 37°C, then, cells in the lower chamber were counted. FIG.4I shows a schematic of the chemotaxis and fugetaxis assays. FIGS.5A-5D depict islet functionality before and after transplant. FIG.5A: Hand-picked islets were tested with glucose stimulated insulin / C peptide secretion (GSIS) assay at 24 hours (h), 48 h and 72 h. FIG.5B: Handpicked islets were cultured with 100 ng / ml and 1 μg / ml prCXCL12 protein to test functionality. Supernatants were collected for analysis by a C-peptide ELISA. The amount of C- peptide was normalized to total protein from lysed cells. Serum from transplanted mice was collected 15-30 days post-transplantation for insulin (FIG.5C) CXCL12 and (FIG.5D) ELISA assays. Control mice were healthy non-diabetic mice. (* p<0.05, ** p<0.01, and *** p<0.001). FIGS.6A-6D depict allo-islet survival graphs, Intraperitoneal Glucose Tolerance Test (IPGTT) data and skin survival graphs. FIG.6A: Kaplan-Meier survival curve, * p<0.05, *** p< 0.001. Animals were subjected to various treatments including only islets, islets with unmodified PEG microgels, and islets transplanted with engineered PEGs containing SA-CXCL12 and / or SA-FasL. Mice with blood glucose >250 mg / dl were considered dead. FIG.6B: Blood glucose readings of animals transplanted with islets and microgels comprising SA-prCXCL12 + SA-FasL, SA-prCXCL12, or SA-FasL and microgels with no conjugated proteins over 180 days. FIG.6C: Glucose response of long-term survival (combination of SA- prCXCL12 and SA-FasL) animals (M1, M2, M3) and control animals without diabetes (C1, C2, C3) were assessed at day 90 post transplantation, mice were fasted for 6 hours and subjected to IPGTT via intraperitoneal glucose (2 g / kg body weight) injection. Plasma glucose levels were determined over 120 minutes. FIG.6D: Long term survival C57BL / 6 recipients (combination treatment, 180 days) were transplanted with BALB / c donor, C57BL / 6 and C3H third-party skin grafts. Graft survival was monitored to evaluate the systemic tolerance over 30 days. FIGS.7A and 7B depict immune phenotyping of lymphocytes andsplenocytes performed two weeks post-transplant using a flow cytometry paneldesigned to assess markers of both humoral and cell-mediated immunity. Combined immune profiling data are presented as normalized percentages of cell subpopulations, visualized in radar plots for each group. FIG.7A: The immune cell populations in the lymphocytes and splenocytes were evaluated in the unstimulated experimental groups (prCXCL12 and combination) and control group (PEG), focusing on CD4⁺ T cells, regulatory T cells (Tregs), effector CD8⁺ T cells, and macrophage subpopulations. Radar plot illustrating the groups: microgels + islets (PEG), prCXCL12 microgels + islets, and prCXCL12 + FasL microgels. FIG.7B: Lymphocytes and splenocytes were isolated and stimulated with PMA / ionomycin for 6-hours or with islet antigen (IA) and pooled islet antigen peptides (PP) for 6- and 12- hours. Immune cell populations in the lymphocytes and splenocytes of transplant recipients (prCXCL12, combination and control group-PEGs) (n = 3) were analyzed two weeks post-transplant. Data represent the distribution of cell subpopulations, presented as normalized percentages for each group in radar plots. The PEG-only group exhibited a more inflammatory profile, marked by increased expression of CD69, IL-2, and IFN-γ, as well as a greater frequency of IFN-γ⁺ macrophages and CD8⁺ T cells, compared to prCXCL12 alone or in combination with FasL (detailed statistics provided in FIG.11A). After BALB / c islet antigens and pooled islet antigen peptide stimulation, CD4+CXCR4+ cell population was higher in the PEG group compared to the combination treatment group at the 12-hour time point in both lymphocytes and splenocytes (detailed statistics provided in FIGS.11B-11C). FIGS.8A and 8B depict an evaluation of immune protection performed by assessing CD4+ T cells, Tregs, and CD31 cell subpopulations in combination treatment (SA-prCXCL12 and SA-FasL) and control group (PEGs) in the graft site. FIG.8A: Immune phenotyping was performed with IHC with fixed tissue from the graft site from transplant animals. Transplant recipients (n=3) were sacrificed 2 weeks post-transplant for analysis of immune cell populations in epididymal fat pad (EFP). The cell count was quantified using image J and the ratio of FOXP3, CD31, CD3, CD8, or F4 / 80 positive cells to DAPI-stained nuclei was calculated, * p<0.05, ** p<0.01, and *** p<0.001 FIG.8B: Representative immunostaining images showed insulin, FOXP3, and CD31 staining. Scale bar = 200 μm. I = Allo-islets, andP = PEGs microgels. For image analysis, stained sections (n=3) were examined, foreach marker, 5–7 representative images per condition were analyzed, and the ratio of marker-positive cell count to DAPI-stained nuclei was calculated. FIG.9 depicts MLR assays (Mixed Lymphocyte Reaction assay) and T cell proliferation. Responder T cells were isolated from the combination treatment group (islets with SA-FasL and SA-prCXCL12, long-term survival animals) and the microgel only group (n = 3 biological replicates per group, with two technical replicates per animal). Carboxyfluorescein succinimidyl ester-labeled (CFSE-labeled) responder cells were cultured with the same number of irradiated (3000 cGy) BALB / c, C57BL / 6 or C3H third-party splenocytes. Two-way Anova test, * p<0.05, ** p<0.01, and *** p<0.001. FIG.10 depicts representative fluorescence imaging of biotin-PEG microgels modified with SA-prCXCL12 and SA-FasL proteins. Following the engineering process, the microgels underwent washing and staining with DyLight 488 Anti- streptavidin antibody for detection of the fusion proteins. After additional washing steps, the engineered microgels were incubated with SA-PE-CF594 to enable the detection and visualization of the microgels. Scale bar as shown is 100 µm. FIGS.11A-11C depict the immune phenotyping of lymph node (LN) and spleen immune cells which was performed using flow panel included markers for both humoral and cell-mediated immunity. Evaluation of immune protection was performed by assessing effector CD8+ T cells (FIG.11A), macrophages (FIG.11B) and CD4+ T cells (FIG.11C) subpopulations in experimental groups (prCXCL12 and Combination) and control groups (Only PEGs). Transplant recipients (n=3) were sacrificed 2 weeks post-transplant for analysis of immune cell populations in lymphocytes and splenocytes. Results are presented as percent of population. (Two- way Anova test, * p<0.1, ** p<0.01, *** p<0.001). The microgel group exhibited a more inflammatory immune profile compared to the combination (SA-prCXCL12 and SA-FasL) or SA-prCXCL12 treatment group alone based on the percentage of populations, suggesting that the treatment can be exerting an immune modulatory effect and influencing T cell and macrophage responses to the allo-islet graft. FIG.12A depicts the immune phenotyping of splenocytes performed two weeks post-transplant using a flow cytometry panel designed to assess markers ofboth humoral and cell-mediated immunity. Combined immune profiling data werepresented as percentages of cell subpopulations (n=3). Evaluation of immune response by assessing CD4+ T cells, effector CD8+ T cells and in macrophage subpopulations in experimental groups (prCXCL12 and Combination) and control groups (Only PEGs). Splenocytes were isolated and stimulated with PMA / ionomycin for 6-hours or with islet antigen (IA) and pooled islet antigen peptides (PP) for 6- and 12-hours. Results are presented as percent of population. * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001. The PEG-only group exhibited a more inflammatory profile, marked by increased expression of CD69, IL-2, and IFN-γ, as well as a greater frequency of IFN-γ⁺ macrophages and CD8⁺ T cells, compared to prCXCL12 alone or in combination with FasL (detailed statistics in FIG.11A). After BALB / c islet antigens and pooled islet antigen peptides stimulation, CD4+CXCR4+ cell population was higher in the PEG group compared to the combination treatment group at the 12-hour time point in both lymphocytes and splenocytes. FIG.12B depicts the immune phenotyping of lymphocytes performed two weeks post-transplant using a flow cytometry panel designed to assess markers of both humoral and cell-mediated immunity. Combined immune profiling data are presented as percentages of cell subpopulations (n=3). Evaluation of immune response by assessing CD4+ T cells, effector CD8+ T cells and macrophage subpopulations in experimental groups (prCXCL12 and Combination) and control groups (Only PEGs). Lymphocytes were isolated and stimulated with PMA / ionomycin for 6-hours or with islet antigen (IA) and pooled islet antigen peptides (PP) for 6- and 12-hours. Results are presented as percent of population. * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001. The PEG-only group exhibited a more inflammatory profile, marked by increased expression of CD69, IL-2, and IFN- γ, as well as a greater frequency of IFN-γ⁺ macrophages and CD8⁺ T cells, compared to prCXCL12 alone or in combination with FasL (detailed statistics in FIG.11A). After BALB / c islet antigens and pooled islet antigen peptides stimulation, CD4+CXCR4+ cell population was higher in the PEG group compared to the combination treatment group at the 12-hour time point in both lymphocytes and splenocytes. FIG.13A depicts a schematic of an optimized allo-islet transplant surgerytechnique. 1200 microgels were modified with SA-prCXCL12 and SA-FasL, and thenmixed to ensure consistency in microgel composition. Additionally, a sandwich method was developed to enhance the direct contact of microgels with islets, thereby maximizing the immune-modulating activity of CXCL12. FIG.13B depicts representative images of the allo-islet transplant surgery technique that was performed, including the sealing of the EFP using a mixture of mouse plasma-thrombin-CaCl2. DETAILED DESCRIPTION The immune rejection of transplanted allogeneic islets, like that of other transplanted organs and tissues, is a complex process, initiated by the local innate immune response to implantation of the graft, which release damage-associated molecular patterns as a result of graft isolation processes, the recognition and presentation of allo- or self-antigens by dendritic cells (DCs) to T cells, and subsequently by the activation and expansion of anti-donor effector T cells (TH1 CD4+ T cells and cytotoxic CD8+ T cells). These effector T cells, which migrate to the transplant site, mediate cytotoxicity against the allo-islet graft and play a central role in islet rejection4. Allo-islet grafting is further challenged by the presence of islet- reactive effector T cells (Teffs) that contributed to the autoimmune destruction of the original host islets in T1D5. In this context, T cell attack against the implanted islets, whose cells contain the same epitopes as those previously the target of T cell attack, does not even require priming from the implanted graft. In this context, graft rejection is rapid58. CD8+ T cells cause islet destruction via perforin / granzyme and Fas / Fas ligand (FasL) interactions6, while TH1 CD4+ T cells produce cytotoxic cytokines such as IFNγ, IL1β, and TNFα7. Approaches that mitigate these effector T-cell functions could support the survival and function of a transplanted organ and / or tissue (e.g., transplanted islets). Physical isolation of islets in the form of microencapsulation or microencapsulation offers some protection from Teff cells but does not entirely eliminate the need for systemic immunosuppression. These encapsulation solutions can also by themselves induce inflammatory foreign body responses and fibrotic overgrowth, leading to islet graft failure8, 57. Moreover, encapsulation impedes thefree diffusion of nutrients and the direct communication necessary for dynamicglucose sensing and insulin secretion9,10, 57. For many patients, the best line of treatment for a disease or disorder can be organ, tissue, and / or cell transplantation. Pancreatic beta cell replacement represents a potential practical treatment for T1D; however this is ultimately contingent on achieving immunoprotection, long-term survival, and optimal function of pancreatic beta cells while ensuring graft recipient safety. The present disclosure demonstrates that the incorporation of SA-prCXCL12 and SA-FasL on the surface of microgels supports long-term allogeneic islet graft survival without systemic immunosuppression. This combinatorial approach successfully induced local immunomodulation, including the promotion of Treg recruitment in the graft, completely abrogating the need for concurrent systemic immune suppression to enable long-term functional survival of the allo-islet graft. In addition, it also facilitated better graft vascularization. Previous studies have demonstrated that CXCL12 can create a long-term immune protective microenvironment that attracts Tregs while repelling Teffs in an alginate encapsulation model without the need for systemic immune release suppression25,26,28. In these studies the alginate matrix enabled continuous release of CXCL12 from the alginate microbead into the surrounding microenvironment over a period of several weeks59. In contrast, using the microgel-based approach disclosed herein, SA-prCXCL12 and SA-FasL were instead captured on the surface of microgels and co-transplanted with allo-islets. The compositions disclosed herein enabled direct presentation of these proteins to immune cells in the graft micoenvironment as well as enabling their release into the graft site microenvironment. In light of the limited functional half-life of CXCL12, the protease-resistant form of CXCL12 (which demonstrated better stability in vitro) was used in the compositions disclosed herein. Data provided herein demonstrated that only by combining SA-prCXCL12 with SA-FasL was it possible to achieve a synergistic effect that led to improved islet survival and long-term immune regulation within the graft environment. Furthermore, the combination of SA-prCXCL12 and SA-FasL abrogated theneed for even the shorter-term systemic immune suppression needed to sustain long term function of the graft when SA-FasL alone was presented on microgels in combination with allo-islets20,43. In addition, unlike the microencapsulation methods that can hinder vascular integration of the islets, the microgel-based system provided in the present disclosure can allow for greater direct vascularization of the islets, a key factor for optimal islet function25,31,36. Therefore, the dual action of CXCL12 and FasL fosters a tolerogenic microenvironment that supports islet graft viability and functionality. As demonstrated herein, immune cells from spleen and lymph nodes (LN) showed a more inflammatory phenotype in the mice receiving allo-islets with microgel only versus the combination (SA-prCXCL12 and SA-FasL) microgel treatment group, suggesting that combination treatment enhanced graft acceptance and local immune isolation of the allo-islets by modulating immune cells response to graft. Immune cells from the combination treatment group demonstrated a reduced inflammatory response compared to the microgel only group and also to islet antigens. Without being bound to any particular theory, the mechanism that distinguishes the effect of SA-FasL microgels alone22and the combination of SA- prCXCL12 and SA-FasL microgels in promoting anatomic site-specific tolerance without systemic immunosuppression can be attributed to differential receptor expression CXCR4 on Teffs, as Tregs are selectively recruited by higher concentrations of CXCL12, whereas CD4+ and CD8+ T cells are repelled by higher concentrations of CXCL1260. Treg recruitment to the graft site is a missing element of FasL microgels by themselves and but is a function provided by CXCL12 release gradients. The selective recruitment of Tregs and repelling of cytotoxic T cells by SA- prCXCL12, coupled with the direct T cell killing function of SA-FasL, is key to maintaining immune tolerance within the graft’s microenvironment. The compositions herein and methods of their use provide a clinically translatable immunomodulatory therapy for T1D islet transplantation, potentially reducing the need for systemic immunosuppression in human recipients. Given the observed long-term graft survival and safety in non-human primate models with individual therapies20,27,28,49, this microgel technology can offer a more favourablerisk-benefit profile by reducing infection risks, organ toxicity, and tumorgenicityassociated with chronic immunosuppression. Biocompatible Polymers and Compositions Thereof Provided herein are biocompatible polymers (e.g., microgels (e.g., biotinylated microgels)) and compositions comprising a plurality of said biocompatible polymers (e.g., microgels) wherein at least one biocompatible polymers (e.g., microgel) of the composition is conjugated to at least one fusion protein comprising a Fas ligand (FasL) polypeptide and at least one biocompatible polymers (e.g., microgel) of the composition is conjugated to at least one fusion protein comprising a protease-resistant C-X-C motif chemokine 12 (CXCL12) polypeptide. As used herein, a microgel is a small, colloidal gel particles composed of three-dimensional polymer networks that are chemically cross-linked. In some instances, a microgel is soft, porous, and sensitive to external stimuli, such as temperature or pH. These properties allow microgels to swell or shrink. In some instances, composition includes a biocompatible polymer that has at least one fusion protein comprising a FasL polypeptide and at least one fusion protein comprising a protease-resistant C-X-C motif chemokine 12 (CXCL12) polypeptide. In some instances, the biocompatible polymer is a microgel. In some instances, the microgel is a biotinylated microgel. Biocompatible Polymers and Methods of Making In some instances, disclosed herein are biocompatible polymers that include hydrogels, which comprise water swollen polymer networks. In some instances, the biocompatible polymers include microgels. Microgels are hydrogel particles that can have many biomedical applications (see, e.g., Alzanbaki et al., Micromachines (Basel).2021 Jan 1;12(1):45). As used herein, “a microgel” refers to a hydrogel with smaller dimensions. In some instances, the biocompatible polymers include at least one biomaterial selected from the group consisting of polyethylene glycol (PEG), methacrylated hyaluronic acid (HAMA), poly(lactic-co-glycolic acid) (PLGA), alginate, gelatin, and gelatin methacrylate (GelMA). In some embodiments, biocompatible polymers disclosed herein can be fabricated from macromers. As usedherein, a “macromer” refers to any polymer or oligomer that has a functional groupthat can take part in further polymerization (e.g., crosslinked to form the biocompatible polymer). Polymers suitable for use in the biocompatible polymers disclosed herein are known in the art (see, e.g., THE POLYMER HANDBOOK, 3rd edition (Wiley, N.Y., 1989); Okano, Ottenbrite, & Park (eds.) (2010) BIOMEDICALAPPLICATIONS OF HYDROGELS HANDBOOK. Springer New York, NY). In some embodiments, biocompatible polymers disclosed herein can be fabricated from polyethylene glycol (PEG) macromers. In some embodiments, a PEG or derivative thereof for use herein can range from about 1 to about 200 kDa (e.g., about 1 to about 150 kDa, about 1 to about 100 kDa, about 1 to about 50 kDa). In some embodiments, a PEG macromer suitable for use herein is a branched or multi-armed PEG macromer. In some embodiments, the multi-armed PEG macromer can have about 2-8 arms, for example, 2, 3, 4, 6, or 8 arms. PEG macromers can be activated by the replacement of the terminal hydroxyl end group to contain a variety of reactive functional end groups. Examples of functional groups that can be attached to the terminal end of the arm of a branched or multi-armed PEG macromer can include, but are not limited to, a primary amine (– NH2), thiol (–SH), carboxyl (–COOH), carbonyl (–CHO), vinyl (–CH=CH2), azide (– N3), and alkyne (–C≡C-H). Each of the functional groups has a corresponding reactive group. For example, a corresponding reactive group to the primary amine functional group can be selected from the group consisting of acyl azide, aldehyde, anhydride, carbodiimide, carbonate, epoxide, fluorobenzene, fluorophenyl ester, imidoester, isocyanate, N-hydroxysuccinimide ester, and sulfonyl chloride; a corresponding reactive group to the thiol functional group can be selected from the group consisting of maleimide, haloacetyl, iodoacetyl, pyridyl disulfide, and vinylsulfone; a corresponding reactive group to the carboxyl functional group can be an amine group; a corresponding reactive group to the carbonyl functional group can be an alkoxyamine and / or a hydrazide; a corresponding reactive group to the vinyl functional group can be selected from the group consisting of acrylate, methacrylate, and thiol; a corresponding reactive group to the azide functional group can be an alkyne and / or a cyclooctyne; and a corresponding reactive group to the alkyne functional group can be an azide and / or a thiol. In some embodiments, biocompatiblepolymers disclosed herein can be fabricated from PEG-maleimide (PEG-MAL)macromers, PEG-acrylate (PEG-Ac) macromers, PEG-vinylsulfone (PEG-VS) macromers, PEG-diacrylate (PEG-DA) macromers, or any combination thereof. In some embodiments, biocompatible polymers disclosed herein can be fabricated from multi-arm PEG-MAL macromers, multi-arm PEG-Ac macromers, multi-arm PEG-VS macromers, multi-arm PEG-DA macromers, or any combination thereof. In some embodiments, the multi-arm PEG macromer for use herein comprises at least eight arms (e.g., an 8-arm PEG). Non-limiting examples of 8-arm PEGs can include 8arm- PEG-Acrylate tripentaerythritol core, 8arm-PEG-Acrylate hexaglycerol core, 8arm- PEG-COOH, 8arm-PEG-Maleimide, 8arm-PEG-NH2 HCl Salt, 8arm-PEG-NH2 HCl Salt, 8arm-PEG-NHS, 8arm-PEG-Norbornene, 8arm-PEG-SH, 8arm-PEG-SH, and 8arm-PEG-Vinylsulfone. In some embodiments, the multi-arm PEG macromer for use herein comprises at least four arms (e.g., a 4-arm PEG). Non-limiting examples of 4-arm PEGs can include 4arm-PEG-Acrylate, 4arm-PEG-COOH, 4arm-PEG- Isocyanate, 4arm-PEG-Maleimide, 4arm-PEG-NH2, 4arm-PEG-NH2 HCl Salt, 4arm- PEG-NHS, 4arm-PEG-SH, and 4arm-PEG-Vinylsulfone. In some embodiments, a multi-arm PEG macromer for use in the biocompatible polymers disclosed herein is a maleimide-terminated four-arm poly(ethylene) glycol (PEG-4MAL) macromer. Methods of making biocompatible polymers suitable for use herein are known in the art (see, e.g., Okano, Ottenbrite, & Park (eds.) (2010) BIOMEDICAL APPLICATIONS OF HYDROGELS HANDBOOK. Springer New York, NY; Headen et al. Adv Mater.2014 May 21;26(19):3003-8; Bashir et al., Polymers (Basel).2020 Nov 16;12(11):2702.; Alzanbaki et al., Micromachines (Basel).2021 Jan 1;12(1):45); Chen et al., Am J Transplantation 14(3) March 2015: 618-627, Projahn et al., J Cell and Mol Medicine 18(5) Feb 2014: 790-800, US Patent App. Pub. Nos 2023 / 0310510; 2023 / 0256115; and 2024 / 0199347, PCT Patent App. Pub. No. WO 2019 / 060541). A biocompatible polymer typically is formed when an organic polymer (natural or synthetic) is crosslinked via covalent, ionic, or hydrogen bonds to create a three- dimensional open-lattice structure which entraps water molecules to form a gel. One of skill in the art can appreciate that biocompatible polymers can be fabricated in numerous shapes and sizes by applying many different fabrication methods. Additionally, methods of fabricating a biocompatible polymer contemplated hereincan vary depending on the polymer chemistry and crosslinking modality. Non-limiting examples of fabrication methods can include ultrasonication, mechanical agitation, high-pressure homogenization, atomization, extrusion through a syringe or nozzle, micromolding, molecular self-association, and microfluidics polymerization. In some embodiments, biocompatible polymers disclosed herein can be fabricated using either batch emulsion or microfluidic droplet generation, depending on the polymer chemistry and crosslinking modality. For PEG-DA biocompatible polymers (Mn about 3.0–6.4k, about 3.2–6.2k, about 3.4–6.0k) and HAMA biocompatible polymers (about 0.5–3% methacrylation, about 1.0–2.5% methacrylation, about 1.0–2.0% methacrylation), photopolymerization can be initiated using lithium phenyl-2,4,6- trimethylbenzoylphosphinate (LAP, about 0.05–0.1% w / v) under about 400-410 nm, or about 405 nanometer (nm) wavelength light. In the batch emulsion method, the aqueous precursor solution can be emulsified into mineral oil containing about 0.5-3% (e.g., about 0.5, 1, 2, or 3% (v / v)) surfactant (e.g., Span 80) using high-shear stirring (about 1000–3000 rpm). In some embodiments, monodisperse droplets can be formed using flow-focusing microfluidic chips with controlled flow rates of aqueous and oil phases. Photo-crosslinking can occur either on-chip (via integrated light sources) or post-collection by external UV or blue light exposure. PLGA biocompatible polymers can be fabricated using a single-emulsion solvent evaporation method. PLGA can be dissolved in dichloromethane or ethyl acetate and emulsified into an aqueous phase containing about 1–2% (w / v) poly(vinyl alcohol) (PVA) via high-speed homogenization. In some embodiments, organic solvents can be evaporated under gentle stirring, and beads can be isolated, washed, and dried. Alginate biocompatible polymers can be prepared by crosslinking sodium alginate (1–2% w / v) with calcium chloride (at least about or about 50 mM-150 mM, or 100 mM). In some embodiments, monodisperse droplets can be generated by electrospraying or microfluidic injection into a calcium bath. In some embodiments, the alginate phase can be emulsified into oil, followed by post-emulsification ionic gelation using soluble or dispersed calcium salts. Gelatin and GelMA biocompatible polymers can be synthesized usingtemperature-controlled emulsification or microfluidic generation. In someembodiments, for gelatin-only biocompatible polymers, the aqueous phase can be emulsified in chilled oil (<4 °C) to induce physical gelation, followed by covalent crosslinking using glutaraldehyde or EDC / NHS chemistry. In some embodiments, for GelMA biocompatible polymers, photopolymerization using lithium phenyl-2,4,6- trimethylbenzoylphosphinate (LAP, about 0.05–0.1% w / v) under about 400-410 nm, or about 405 nanometer (nm) wavelength light can be performed. Preferably, biocompatible polymers disclosed herein are fabricated using microfluidics polymerization. Microfluidic platforms offer superior control over the size and morphology of biocompatible polymers, cell co-culture with a precise control over the number of cells of each type per single bead, high encapsulation efficiency due to low shear forces during droplet generation, integration of particle generation and manipulation within a single chip, continuous processing, and operation under sterile conditions (see, e.g., Chet et al., Molecules.2021 Jun 20;26(12):37520). In some embodiments, biocompatible polymers disclosed herein are fabricated by droplet segmentation using a flow-focusing microfluidic device (see, e.g., Headen et al. Adv Mater.2014 May 21;26(19):3003-8). Biocompatible polymers are generally prepared using a two-step process consisting of the formation of an emulsion droplets containing a gel-forming polymer solution (e.g., a PEG macromer solution, a biotinylated PEG macromer solution) and the crosslinking of polymer chains within the droplets (see, e.g., Chet et al., Molecules.2021 Jun 20;26(12):37520). Various chemical (e.g., crosslinking by chemical reaction of complementary groups, polymer–polymer crosslinking, high energy irradiation and enzyme incorporation) and physical (e.g., charge interactions, crystallization and stereocomplex formation) approaches can be employed for crosslinking the biocompatible polymers disclosed herein. In some embodiments, a crosslinking agent can be a natural crosslinking agent (e.g., vanillin, citric acid, gallic acid, ferulic acid and genipin). In some embodiments, a crosslinking agent can be a synthetic crosslinking agent (e.g., N,N′-methylenebisacrylamide, ethylene glycol dimethacrylate, poly (ethylene glycol) diacrylates, epichlorohydrin, glutaraldehyde, polymerizable polyphosphate, 1,2,3,4-butanetetracarboxylic dianhydride and 2- chloro-1-methylpyrinium iodide). The crosslinker is ultimately selected based on thepolymer (e.g., PEG macromer) being used to form the biocompatible polymer. Insome embodiments, a polymer for use herein can include one or more moieties that enable its crosslinking to other polymer molecules via a Michael-type addition reaction between the polymer / macromer and crosslinker. In some embodiments, the polymer (e.g., PEG macromer) includes one or more moieties that enable its crosslinking to other polymer molecules via a Michael- type addition reaction between the polymer (e.g., PEG macromer) and crosslinker. Michael type-addition or Michael addition is a facile reaction between nucleophiles (Michael donors) and activated electrophilic olefins or alkynes (Michael acceptors) whereby a nucleophile is added across a carbon–carbon multiple bond. Michael addition acceptors can include acrylate esters, acrylonitrile, acrylamides, maleimides, alkyl methacrylates, cyanoacrylates and vinyl sulfones. Michael-type additions are advantageous in that they generally include mild reaction conditions, highly regioselective and efficient click chemistry, and favorable reaction rates (see, e.g., Hu et al., Biomater Sci.2019 Feb 26;7(3):843-855.). For construction of biocompatible polymers, Michael addition often refers to thiol containing polymers added to the activated α,β-unsaturated carbonyl polymers under basic conditions. As thiols are present in proteins in cysteine residues, hydrogels can be easily synthesized between proteins and polymers. Therefore, in some embodiments, the polymer or macromer, for example a PEG macromer or derivative thereof, is modified to include a moiety that can facilitate crosslinking of two or more polymers by Michael-type addition. For example, moieties suitable for Michael-type addition include, but are not limited to, maleimides, vinyl sulfones, and acrylates. Other suitable reactive chemistries include N-hydroxysuccinimide, succinimidyl propionate, thiol-ene and other “click” chemistries. In some embodiments, biocompatible polymers disclosed herein comprise a macromer that includes one or more maleimide groups (e.g., PEG-MAL). In some embodiments, the crosslinker used herein can include one or more thiols, and the Michael-type addition reaction is between the maleimide groups on the polymer / macromer and thiols on the crosslinker. Fast reaction kinetics renders this hydrogel advantageous for microfluidic encapsulation, allowing for short residence time on chip, and minimizing cell stress. This Michael-type addition reaction requiresno free radicals and is cytocompatible (Phelps, et al., Advanced Materials, 24(1):64-70 (2012)). In some embodiments, a cross linker can comprise a cysteine-containing peptide. Non-limiting examples of peptide crosslinkers suitable for use herein include: GCRDVPMSMRGGDRCG (SEQ ID NO: 19); KCGPQGIWGQCK (SEQ ID NO: 20); KCVPMSMRGGCK (SEQ ID NO: 21); KCYGPQGIWGQYCK (SEQ ID NO: 22); YGKCYGPQGIWGQYCKGY (SEQ ID NO: 23); GCRDGPQGIAGQDRCG (SEQ ID NO: 24); GCRDGPQGIWGQDRCG (SEQ ID NO: 25), or any fragment or variant thereof. In some embodiments, a cross linker for use herein is dithiothreitol (DTT). The biocompatible polymers (e.g., microgels (e.g., biotinylated microgels)) disclosed herein can comprise a diameter ranging from about 100 to 300 microns, about 125 to 200 microns, about 125 to 175 microns. In some instances, the diameter is about 150 microns. In some instances, the size of the biocompatible polymer is about the same size as an islet cell. Biocompatible polymer size can be controlled dementing on the method used for their fabrication. For example, for batch emulsions, size can be controlled by modulating emulsification parameters including stirring speed, oil-to-aqueous phase ratio, and / or surfactant concentration. In single emulsion solvent systems (e.g., PLGA), size can be adjusted by emulsification time, and / or PVA concentration. Electrospray or micro-extrusion techniques for alginate and gelatin can be optimized by tuning voltage, flow rate, nozzle dimensions, and / or calcium concentration (for alginate). Microfluidic systems offer the highest precision and can be used to control droplet size by adjusting the flow rate ratios between the dispersed and continuous phases, and by selecting appropriate nozzle geometries (e.g., about 10–75 µm orifice widths). In some embodiments, biocompatible polymers (e.g., microgels) disclosed herein can comprise a diameter of at least about 120, 130, 140, 150, 160, 170, 180, 190, or 200 microns. The size distribution of the biocompatible polymers (e.g., biotinylated microgels) disclosed herein can be uniform (monodisperse). In certain embodiments, size distribution the biocompatible polymers (e.g., biotinylated microgels) disclosed herein can be non-uniform (polydisperse). The National Institute of Standards and Technology (NIST) considers a particle distribution to be “monodisperse” if at least 90% of the distribution lies within 5% of the median size (Particle SizeCharacterization, Special Publication 960-1, January 2001).Biocompatible polymer size, morphology, and polydispersity can be confirmed by optical / confocal microscopy with automated image analysis, and validated using dynamic light scattering (DLS), Coulter counter, and laser diffraction analysis, depending on material compatibility. In some embodiments, the biocompatible polymers disclosed herein are biotinylated microgels. As used herein “biotin” includes biotin-containing moieties that are able to bind to surfaces, such as cell surfaces, such as NHS-biotin and EZ- Link™ Sulfo-NHS-LC-Biotin (Pierce). Biotin and protein-reactive forms of biotin are available commercially. To generate a biocompatible polymer (e.g., a biotinylated microgel), at least one or more of the reactive groups of a macromer (e.g., a PEG macromer, e.g., a PEG-maleimide (PEG-MAL) macromer) can be functionalized with biotin. For example, a PEG-MAL macromer, which comprises a maleimide the reactive group, can be functionalized with biotin when reacted with biotin-PEG-thiol. In some embodiments, biotinylated microgels disclosed herein can be produced by reacting biotin-PEG-thiol with a PEG macromer comprising at least one reactive group selected from the group consisting of maleimide, haloacetyl, iodoacetyl, pyridyl disulfide, and vinylsulfone. In some embodiments, biotinylated microgels disclosed herein can be produced by reacting biotin-PEG-thiol with a PEG macromer comprising maleimide. In some embodiments, biotinylated microgels disclosed herein can be produced by reacting biotin-PEG-thiol with PEG-4MAL macromer. In some embodiments, biotinylated microgels disclosed herein can be conjugated to one or more fusion proteins via an avidin and / or streptavidin (“SA”) moiety. Fusion Proteins The biocompatible polymers (e.g., biotinylated microgels) disclosed herein can be used to deliver one or more proteins of interest to the desired location (e.g., at or near the site of graft transplantation) in a subject. A protein of interest can comprise a polypeptide (e.g., CXCL12, FasL) fused to at least one avidin and / or streptavidin (“SA”) moiety. A “polypeptide” as understood herein refers to a polymer of amino acid residues (natural or unnatural) linked together most often by peptide bonds. As such, a polypeptide can refer to proteins and peptides of any size, structure, or function. Non-limiting examples of polypeptides can include geneproducts, naturally occurring polypeptides, synthetic polypeptides, homologs,orthologs, paralogs, fragments and other equivalents, analogs, and variants thereof. A variant of the polypeptide refers to a polypeptide having an amino acid sequence that differs from a native or reference amino acid sequence. The amino acid sequence of such variant polypeptides can have substitutions, deletions, and / or insertions at certain positions within the amino acid sequence, as compared to a native or reference sequence. Variant polypeptides of the present disclosure can possess at least about 50% identity to a native or reference sequence. The fusion protein comprising an avidin and / or SA moiety is conjugated to a biocompatible polymer (e.g., a biotinylated microgel) disclosed herein via the interaction between biotin and avidin and / or SA moiety. Biotin has an extremely high affinity for both SA (1013M−1) and avidin (1015M−1). An advantageous feature of fusion proteins comprising an avidin and / or SA moiety is their ability to exist as tetramers and even higher-order structures due to the inherent physical-chemical properties of streptavidin / avidin (Pahler et al., J. Biol. Chem.1987; 262:13933- 13937). A streptavidin moiety for use herein can be sourced from Streptomyces avidinii or a recombinant streptavidin. Recombinant Streptavidin - amino acid sequence (SEQ ID NO: 8) ! In some embodiments, a fusion protein disclosed herein can comprise a streptavidin comprising an amino acid sequence that is at least about or about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical to SEQ ID NO: 5. In some embodiments, a fusion protein disclosed herein can comprise a streptavidin moiety comprising an amino acid sequence of SEQ ID NO: 5. In some embodiments, a fusion protein disclosed herein can comprise a streptavidin moiety consisting of the amino acid sequence of SEQ ID NO: 5. In some embodiments, a fusion protein disclosed herein can comprise a nucleic acid sequence that is at least about or about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical to SEQ ID NO: 3. In some embodiments, a fusion protein disclosed herein can comprise a nucleic acid sequence comprising SEQ ID NO: 3. In some embodiments, a fusion protein disclosed herein can comprise a the nucleic acid sequence of SEQ ID NO: 3. In some embodiments, a fusion protein disclosed herein can comprise a streptavidin comprising an amino acid sequence that is at least about or about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical to SEQ ID NO: 8. In some embodiments, a fusion protein disclosed herein can comprise a streptavidin moiety comprising an amino acid sequence of SEQ ID NO: 8. In some embodiments, a fusion protein disclosed herein can comprise a streptavidin moiety consisting of the amino acid sequence of SEQ ID NO: 8. In some embodiments, a fusion protein disclosed herein can comprise a nucleic acid sequence that is at least about or about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical to SEQ ID NO: 4. In some embodiments, a fusion protein disclosed herein can comprise a nucleic acid sequence comprising SEQ ID NO: 4. In some embodiments, a fusion protein disclosed herein can comprise the nucleic acid sequence of SEQ ID NO: 4. The avidin and / or SA moiety as used in the fusion proteins herein can comprise a SA and / or avidin fragment and / or variant which retains substantial binding activity for biotin (e.g., retains at least 50% or more of the binding affinity of native SA or avidin). Such fragments can include “core streptavidin” a truncated version of the full-length streptavidin polypeptide which can include streptavidin residues 13- 138, 14-138, 13-139, 14-139, 16-133. See, e.g., Pahler et al., J. Biol. Chem., 262: 13933-37 (1987); and Sano et al., J Biol Chem.270(47): 28204-09 (1995). Mutants of streptavidin and core forms of strepavidin which retain substantial biotin binding activity or increased biotin binding activity also can be used. See, e.g., Chilcoti et al., Proc Natl Acad Sci, 92(5): 1754-58 (1995), Reznik et al., Nat Biotechnol, 14(8): 1007-11(1996). For example, mutants with reduced immunogenicity, such as mutants mutated by site-directed mutagenesis to remove potential T cell epitopes or lymphocyte epitopes, can be used. See Meyer et al., Protein Sci., 10: 491-503 (2001). Likewise, mutants of avidin and core forms of avidin which retain substantial biotin binding activity or increased biotin binding activity also can be used. See Hiller et al., J Biochem, 278: 573-85 (1991); and Livnah et al., Proc Natl Acad Sci USA 90: 5076- 80 (1993). Examples include: Core SA (SEQ ID NO: 6): Modified Core SA (SEQ ID NO: 7): In some embodiments, a fusion protein disclosed herein can comprise a streptavidin core moiety comprising an amino acid sequence that is at least about or about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical to SEQ ID NO: 6 or 7. In some embodiments, a fusion protein disclosed herein can comprise a streptavidin core moiety comprising an amino acid sequence of SEQ ID NO: 6 or 7. In some embodiments, a fusion protein disclosed herein can comprise a streptavidin core moiety consisting of the amino acid sequence of SEQ ID NO: 6 or 7. In some embodiments, a fusion protein disclosed herein can comprise at least one avidin moiety. Examples of amino acid sequences of and nucleic acid sequences encoding for avidin moieties include: Gallus gallus avidin (AVD) – amino acid sequence (SEQ ID NO: 9) Gallus gallus avidin (AVD) – nucleic acid sequence (SEQ ID NO: 10) Gallus gallus avidin (AVD) – mRNA (SEQ ID NO: 11) Gallus gallus avidin (AVR1 gene) (SEQ ID NO: 12) Gallus gallus avidin (AVR2 gene) (SEQ ID NO: 13) In some embodiments, a fusion protein disclosed herein can comprise an avidin moiety comprising an amino acid sequence that is at least about or about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical to SEQ ID NO: 9. In some embodiments, a fusion protein disclosed herein can comprise an avidin moiety comprising an amino acid sequence of SEQ ID NO: 9. In some embodiments, a fusion protein disclosed herein can comprise an avidin moiety consisting of the amino acid sequence of SEQ ID NO: 9. In some embodiments, a fusion protein disclosed herein can comprise a nucleic acid sequence that is at least about or about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical to one of SEQ ID NOS: 10-13. In some embodiments, a fusion protein disclosed herein can comprise a nucleic acid sequence comprising a sequence selected from one of SEQ ID NOS: 10-13. In some embodiments, a fusion protein disclosed herein can comprise a nucleic acid sequence consisting of one of SEQ ID NOS: 10-13. The streptavidin moiety and / or avidin moiety is fused to a polypeptide of interest using a linker. In some embodiments, the linker is a flexible peptide linker. In some embodiments, the linker is a flexible linker that can consist of a sequence of consecutive amino acids that typically include at least one glycine and at least one serine. Non-limiting examples of linkers suitable for use herein include GGGGS (SEQ ID NO: 28), GGGGSGGGGS (SEQ ID NO: 29), GGGGSGGGGSGGGGS (SEQ ID NO: 30), and GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 31). In some embodiments, the streptavidin moiety and / or avidin moiety can be fused to the N- terminus and / or C-terminus of the polypeptide of interest (e.g., pr CXCL12, FasL). In some embodiments, the C-terminus of the streptavidin moiety and / or avidin moiety is fused to the N-terminus of the polypeptide of interest. A fusion protein disclosed herein can further comprise a tag. Examples of a tag for use herein include a peptide tag for protein isolation / purification such as FLAG-tag (amino acid sequence: RSDYKDDDDK (SEQ ID NO: 26) and / or a histidine tag (amino acid sequence: HHHHHH (SEQ ID NO: 27). The tag can be linked, for example, to the N-terminus and / or C-terminus of the fusion protein. In some embodiments, the C-terminus of a tag is joined to the N-terminus of the SA and / or avidin moiety of the fusion protein. Provided herein are methods of generating the fusion proteins disclosed. Methods include herein introducing a fusion protein (e.g., SA- CXCL12, SA-pr CXCL12, SA-FasL) in a nucleic acid that encodes them into a cell (e.g., a target cell). In order to express a fusion protein disclosed herein, a sequence encoding the fusion protein can be subcloned into an expression vector that contains a promoter to direct transcription. Suitable bacterial and eukaryotic promoters are well known in the art and described, e.g., in Sambrook et al., MOLECULAR CLONING, A LABORATORY MANUAL (3d ed.2001); Kriegler, GENE TRANSFER AND EXPRESSION: A LABORATORY MANUAL (1990); and CURRENT PROTOCOLS IN MOLECULAR BIOLOGY (Ausubel et al., eds., 2010). Bacterial expression systems for expressing the fusion proteins are available in, e.g., E. coli, Bacillus sp., and Salmonella (see, e.g., Palva et al., 1983, Gene 22:229-235). Kits for such expression systems are commercially available. Eukaryotic expression systems for mammalian cells, yeast, and insect cells are well known in the art and are also commercially available. Standard transfection methods can be used herein to produce bacterial, mammalian, yeast or insect cell lines that express large quantities of protein, which are then purified using standard techniques (see, e.g., Colley et al., 1989, J. Biol. Chem., 264: 17619-22; GUIDE TO PROTEIN PURIFICATION, IN METHODS IN ENZYMOLOGY, vol.182 (Deutscher, ed., 1990)).Transformation of eukaryotic and prokaryotic cells are performed according tostandard techniques (see, e.g., Morrison, 1977, J. Bacteriol.132:349-351; Clark- Curtiss & Curtiss, Methods in Enzymology 101 :347-362 (Wu et al., eds, 1983). Any of the known procedures for introducing foreign nucleotide sequences into host cells can be used in the present disclosure. Examples include the use of calcium phosphate transfection, polybrene, protoplast fusion, electroporation, nucleofection, liposomes, microinjection, naked DNA, plasmid vectors, viral vectors, both episomal and integrative, and any of the other well-known methods for introducing cloned genomic DNA, cDNA, synthetic DNA or other foreign genetic material into a host cell (see, e.g., Sambrook et al., MOLECULAR CLONING, A LABORATORY MANUAL (3d ed.2001); Kriegler, GENE TRANSFER AND EXPRESSION: A LABORATORY MANUAL (1990)). In some embodiments, a fusion protein disclosed herein can comprise a CXCL12 polypeptide (e.g., a protease-resistant CXCL12 polypeptide) fused to at least one avidin and / or streptavidin (“SA”) moiety. In some embodiments, fusion protein disclosed herein can comprise a FasL polypeptide fused to at least one avidin and / or streptavidin (“SA”) moiety. CXCL12 CXCL12 is a biological factor with potential to reprogram local immune responses against islets. CXCL12 is a small (8 kDa) chemokine that mediates cell signaling through its binding to the CXCR4 and CXCR7 chemokine receptors. CXCL12 signaling plays pivotal roles in inflammation, immune surveillance and the development and / or regeneration of diverse tissues and organs. This chemokine not only promotes vascularization of the pancreatic islet50and exerts direct pro-survival effects on them51-53but it alters trafficking and behavior of immune cells in the local islet environment. It directly alters T cell adhesion to constituent islet cells54,55, can prevent inflammatory fibrotic foreign body responses to islets50,54, and can differentially repel T cells effector T cells while recruiting CD4+CD25+FoxP3+regulatory T cells (Treg)52,53. These differential effects correlate with the expression levels of CXCR4 on different T cell types and the structure of the concentration gradient of the chemokine itself53. High concentrations of CXCL12 (1 mg / ml and above) solicit chemorepellent or fugetactic responses from CD8+T cells whereas gradients with lower peak CXCL12 concentrations (10 – 100 ng / ml) elicit achemoattractant response for this cell subpopulation. Treg cells expressing lowerlevels of CXCR4 on their surface are selectively attracted toward the source of even high CXCL12 concentration gradients53. Additionally, CXCL12 promotes vascularization, potentially enhancing islet integration and function in the host12,14,48. The amino acid sequence of CXCL12 is: CXCL12 (wild type) – (SEQ ID NO: 1) GKPVSLSYRCPCRFFESHVARANVKHLKILNTPNCALQIVARLKNNNRQVCIDPKLK WIQEYLEKALNK In some embodiments, a fusion protein disclosed herein can comprise a CXCL12 polypeptide comprising an amino acid sequence that is at least about or about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical to SEQ ID NO: 1. In some embodiments, a fusion protein disclosed herein can comprise a CXCL12 polypeptide comprising an amino acid sequence of SEQ ID NO: 1. In some embodiments, a fusion protein disclosed herein can comprise a CXCL12 polypeptide consisting of the amino acid sequence of SEQ ID NO: 1. CXCL12 has poor stability and a short half-life in vivo as it can be subject to proteolytic degradation by various proteases present in the cellular environment. Different proteases, such as matrix metalloproteinases (MMPs), serine proteases, and cysteine proteases, have been implicated in the proteolytic processing of CXCL12. MMP-2 and MMP-9 have been shown to degrade CXCL12, thereby reducing its stability and half-life. Additionally, dipeptidyl peptidase-4 (DPP-4) has been reported to cleave and inactivate CXCL12, further influencing its half-life49–52. The presence of protease inhibitors or specific mutations in CXCL12 that affect protease recognition sites can modulate its susceptibility to proteolytic degradation and impact its half-life. These factors can be important in regulating the availability and function of CXCL12 in various biological processes50–53. In general, the half-life of CXCL12 has been found to range from an hour to several hours depending on the experimental setting and the specific tissue or cell type in which it is expressed. In vitro studies utilizing purified CXCL12 have reported a half-life of approximately 2 to 4 hours. In contrast, some in vivo studies using animal models have demonstrated a shorter half-life of around 20 minutes51,52. Additionally, active MMP2 and MMP9 are increased 6-fold and 14-fold, respectively, in lesions of diabetic patients compared to non-diabetic conditions49. Compositions (e.g., microgels) provided herein can comprise a protease-resistant variant of CXCL12 to enhance the stability and half-life of CXCL12. The amino acid sequence of protease-resistant CXCL12 (prCXCL12) is: prCXCL12 (protease-resistant) – (SEQ ID NO: 2) SKPVVLSYRCPCRFFESHVARANVKHLKILNTPNCALQIVARLKNNNRQVCIDPKLK WIQEYLEKALNK In some embodiments, a fusion protein disclosed herein can comprise a CXCL12 polypeptide comprising an amino acid sequence that is at least about or about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical to SEQ ID NO: 2. In some embodiments, a fusion protein disclosed herein can comprise a CXCL12 polypeptide comprising an amino acid sequence of SEQ ID NO: 2. In some embodiments, a fusion protein disclosed herein can comprise a CXCL12 polypeptide consisting of the amino acid sequence of SEQ ID NO: 2. In some embodiments, a fusion protein disclosed herein can comprise a peptide tag, a streptavidin or avidin moiety, and a CXCL12 polypeptide or a protease- resistant CXCL12 polypeptide. In some embodiments, a fusion protein disclosed herein can comprise a peptide tag, a streptavidin core moiety, a flexible linker, and a CXCL12 polypeptide or a protease-resistant CXCL12 polypeptide. In some embodiments, a fusion protein disclosed herein can comprise a FLAG tag, a streptavidin core moiety, a flexible linker, and a CXCL12 polypeptide or a protease- resistant CXCL12 polypeptide. Examples of amino acid sequences of fusion proteins (e.g., SA-CXCL12 and SA-prCXCL12) disclosed herein are provided below where the underlined amino acids represent the FLAG tag, italicized amino acids represent the linker, and bold amino acids represent the SA core: In some instances, the sequence for CXCL12 is, comprises, or consists of: This sequence (i.e., SEQ ID NO: 40) is also located at the terminal ends of SEQ ID NO: 16 or SEQ ID NO:17. In some embodiments, a fusion protein disclosed herein can comprise an amino acid sequence that is at least about or about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical to SEQ ID NO: 16 or 17. In some embodiments, a fusion protein disclosed herein can comprise an amino acid sequence of SEQ ID NO: 16. In some embodiments, a fusion protein disclosed herein can comprise an amino acid sequence of SEQ ID NO: 17. In some instances, any one of the biocompatible polymers or microgels includes a CXCL12 moiety (e.g., protease-resistant CXCL12) and a FasL moiety. FasL FasL is an mmunomodulator that prevents the rejection of islets in allogeneic recipients with an autoimmune background12–23. The Fas / FasL pathway holds significant potential for modulating immune responses to auto- and alloantigens. Transplantation tolerance in humans has been challenging primarily due to the presence of a large pool of memory T cells24–27that are resistant to immunomodulatory protocols targeting them for functional inactivation and / or physical depletion24,26,28–30. Memory CD4+ and CD8+ T cells in rodents, non-human primates, and humans15,31,32express Fas on the surface15. FasL contributes to tolerance by initiating a secondary immunoregulatory pathway involving phagocytes and cytokines such as TGF-β and IL-10, which generate Tregs (CD4+CD25+FOXP3+), which play a crucial role in the tolerogenic efficacy of FasL33–38. Treg cells utilize FasL to eliminate Teff cells and DCs as a suppression mechanism39,40. In prediabetic NOD mice, engineered Treg cells expressing FasL, termed "killer" Treg cells, attenuate autoimmune insulitis12,14. It has also been demonstrated that SA-FasL eliminates NOD Teff cells but not Treg cells41, and that FoxP3+ Treg cells are critical to the tolerogenic efficacy of SA- FasL35,42,43. Diabetic non-human primates (DNHP) treated with a co-transplantation ofallogeneic islets and SA-FasL-presenting microgel exhibited robust glycemic control,sustained C-peptide levels, and graft survival over six months, with an increased number of FoxP3+ cells associated with the graft, indicating localized tolerance44. The amino acid sequence of FasL and an extracellular domain of FasL are: In some embodiments, a fusion protein disclosed herein can comprise a FasL polypeptide comprising an amino acid sequence that is at least about or about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical to SEQ ID NO: 14 or 15. In some embodiments, a fusion protein disclosed herein can comprise a FasL polypeptide comprising an amino acid sequence of SEQ ID NO: 14 or 15. In some embodiments, a fusion protein disclosed herein can comprise a FasL polypeptide consisting of the amino acid sequence of SEQ ID NO: 14 or 15. In some embodiments, a fusion protein disclosed herein can comprise a peptide tag, a streptavidin or avidin moiety, and a FasL polypeptide. In some embodiments, a fusion protein disclosed herein can comprise a peptide tag, a streptavidin core moiety, a flexible linker, and a FasL polypeptide. In some embodiments, a fusion protein disclosed herein can comprise a FLAG tag, a streptavidin core moiety, a flexible linker, and a FasL polypeptide. An example of an amino acid sequence of a fusion protein (e.g., SA-FasL) disclosed herein is provided below where the underlined amino acids represent the FLAG tag, italicized amino acids represent the linker, and bold amino acids represent the SA core: In some embodiments, a fusion protein disclosed herein can comprise an amino acid sequence that is at least about or about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical to SEQ ID NO: 18. In some embodiments, a fusion protein disclosed herein can comprise an amino acid sequence of SEQ ID NO: 18. In some embodiments, the fusion protein disclosed herein can comprise a matrix metalloproteinase resistant FasL polypeptide. As used herein, the matrix metalloproteinase resistant FasL polypeptide is a form of FasL in which the extracellular domain of FasL lacks MMP sensitive sites. See, e.g., Yolcu et al., Immunity.2002 Dec;17(6):795-808. In some instances, any one of the biocompatible polymers or microgels includes SA-FasL and CXCL12 (e.g., protease-resistant CXCL12). Plurality of Biotinylated Microgels The biotinylated microgels of the present disclosure can be combined into a composition comprising a plurality of biotinylated microgels for use herein. In some embodiments, each biotinylated microgel within the composition comprises at least one fusion protein as disclosed herein, wherein the fusion protein comprises a polypeptide of interest fused to at least one avidin and / or streptavidin (“SA”) moiety. In some embodiments, each biotinylated microgel within the composition comprises at least one fusion protein as disclosed herein, wherein the fusion protein comprises a CXCL12 polypeptide fused to at least one avidin and / or SA moiety (e.g., SA- CXCL12). In some embodiments, each biotinylated microgel within the composition comprises at least one fusion protein as disclosed herein, wherein the fusion protein comprises a protease-resistant CXCL12 polypeptide fused to at least one avidin and / or SA moiety (e.g., SA-prCXCL12). In some embodiments, each biotinylated microgel within the composition comprises at least one fusion protein as disclosed herein, wherein the fusion protein comprises a FasL polypeptide fused to at least one avidin and / or SA moiety (e.g., SA-FasL). In some embodiments, the plurality of biotinylated microgels comprises biotinylated microgels conjugated to SA-prCXCL12 and biotinylated microgels conjugated to SA-FasL. In some embodiments, the plurality of biotinylated microgels comprises between 1% and 80% (w / w) biotinylated microgels conjugated to SA- prCXCL12. In some embodiments, the plurality of biotinylated microgels comprises between 1% and 80% (w / w) biotinylated microgels conjugated to SA-FasL. In some embodiments, the plurality of biotinylated microgels comprises between 1% and 80% (w / w) biotinylated microgels conjugated to SA-prCXCL12 and between 1% and 80% (w / w) biotinylated microgels conjugated to SA-FasL. In some embodiments, the plurality of biotinylated microgels comprises at least about or about 40%, 45%, 50%, 55%, or 60% biotinylated microgels conjugated to SA-prCXCL12. In some embodiments, the plurality of biotinylated microgels comprises at least about or about 40%, 45%, 50%, 55%, or 60% biotinylated microgels conjugated to SA-FasL. In some embodiments, the plurality of biotinylated microgels comprises at least about or about 40%, 45%, 50%, 55%, or 60% biotinylated microgels conjugated to SA- prCXCL12 and at least about or about 40%, 45%, 50%, 55%, or 60% biotinylated microgels conjugated to SA-FasL. In some embodiments, the plurality of biotinylated microgels comprises at least about 50% biotinylated microgels conjugated to SA- prCXCL12 and at least about or about 50% biotinylated microgels conjugated to SA- FasL. In some embodiments, the plurality of biotinylated microgels comprises a ratio of biotinylated microgels conjugated to SA-prCXCL12: biotinylated microgels conjugated to SA-FasL of 1:1, 2:1, 3:1, 1:2, or 1:3. In some embodiments, the plurality of biotinylated microgels comprises a ratio of biotinylated microgels conjugated to SA-prCXCL12: biotinylated microgels conjugated to SA-FasL of 1:1. Compositions comprising a plurality of biotinylated microgels are contemplated herein to provide a sustained release of at least one of the polypeptides of interest (e.g., prCXCL12, FasL) conjugated to the biotinylated microgels. In some embodiments, a composition comprising a plurality of biotinylated microgels disclosed herein can provide a sustained release of at least one of the polypeptides of interest (e.g., prCXCL12, FasL) over a period of at least about or about 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, 1.5 months, or 2 months. Insome embodiments, a composition comprising a plurality of biotinylated microgelsdisclosed herein can provide a sustained release of prCXCL12 over a period of at least about or about 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, 1.5 months, 2 months, 2.5 months, 3 months, 3.5 months, 4 months, 4.5 months, 5 months, 5.5 months, 6 months, or more than about 6 months. In some embodiments, a composition comprising a plurality of biotinylated microgels disclosed herein can provide a sustained release of FasL over a period of at least about or about 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, 1.5 months, 2 months, 2.5 months, 3 months, 3.5 months, 4 months, 4.5 months, 5 months, 5.5 months, 6 months, or more than about 6 months. In some embodiments, a composition comprising a plurality of biotinylated microgels disclosed herein can provide a sustained release of both prCXCL12 and FasL over a period of at least about or about 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, 1.5 months, 2 months, 2.5 months, 3 months, 3.5 months, 4 months, 4.5 months, 5 months, 5.5 months, 6 months, or more than about 6 months. In some embodiments, sustained release of at least one of the polypeptides of interest (e.g., prCXCL12, FasL) from the compositions comprising a plurality of biotinylated microgels begins once the composition is placed in a physiological condition (e.g., a cell culture medium at 37°C, or transplanted into a subject, e.g., a human subject in need thereof). Pharmaceutical Compositions and Methods of Administration The methods described herein include the use of pharmaceutical compositions comprising or consisting of at least one of the biotinylated microgels conjugated to a polypeptide of interest (e.g., SA-prCXCL12, SA-FasL) disclosed herein, and / or compositions comprising a plurality of biotinylated microgels disclosed herein. Pharmaceutical compositions typically include a pharmaceutically acceptable carrier. As used herein the language “pharmaceutically acceptable carrier” includes saline, solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. A listing of active compounds and specific drugs suitable for useherein as supplementary active compounds can be found in The Merck Index Online;Royal Society of Chemistry, 2025; rsc.org / merck-index (accessed March 12, 2025), and the United States Pharmacopeia-47 / National Formulary-47, published by the United States Pharmacopeial Convention, Inc., Rockville Md., 2024. In some embodiments, a supplementary active compound can be one known in the art to treat and / or alleviate a symptom associated with graft vs. host disease (GvHD). In some embodiments, a supplementary active compound can be one known in the art to treat and / or alleviate a symptom associated with T1D. Pharmaceutical compositions are typically formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous (i.v.), intradermal, subcutaneous, oral (e.g., inhalation), transdermal (topical), transmucosal, and rectal administration. In some embodiments, a pharmaceutical composition of the present disclosure is formulated for delivery to the lymph system (e.g., the spleen). In some embodiments, a pharmaceutical composition of the present disclosure is formulated for delivery to the bone marrow. In some embodiments, a pharmaceutical composition of the present disclosure is formulated for delivery to the anterior chamber of the eye. In some embodiments, a pharmaceutical composition of the present disclosure is formulated for intra-hepatic delivery (e.g., intra-hepatic infusion). In some embodiments, a pharmaceutical composition of the present disclosure is formulated for delivery to the omentum (e.g., extra-hepatic; see, e.g., Schaschkow et al., Cell Transplant.2018 Aug;27(8):1289- 1293). In some embodiments, a pharmaceutical composition of the present disclosure is formulated for local delivery at the site of transplantation. Methods of formulating suitable pharmaceutical compositions are known in the art, see, e.g., Remington: The Science and Practice of Pharmacy, 21st ed., 2005; and the books in the series Drugs and the Pharmaceutical Sciences: a Series of Textbooks and Monographs (Dekker, NY). For example, solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such asethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates andagents for the adjustment of tonicity such as sodium chloride or dextrose. pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic. Pharmaceutical compositions suitable for injectable use can include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, NJ) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringability exists. It should be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyetheylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it can be preferable to include isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent that delays absorption, for example, aluminum monostearate and gelatin. Sterile injectable solutions can be prepared by incorporating the active compound in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle, which contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying andfreeze-drying, which yield a powder of the active ingredient plus any additionaldesired ingredient from a previously sterile-filtered solution thereof. Pharmaceutical compositions disclosed herein can be formulated for controlled release of the polypeptide of interest (e.g., prCXCL12, FasL). For example, controlled release of the active agent of interest can be achieved through encapsulation of microgels conjugated to said polypeptide of interest and / or fusion proteins disclosed herein. In some embodiments, the microgels and / or fusion proteins disclosed herein can be encapsulated in liposomes, microspheres, nanoparticles, and the like. See, e.g., U.S. Patent No.5,413,797; Timko et al., Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1349-54; Merkus, Henk G., Gabriel MH Meesters, and Wim Oostra, eds. PARTICLES ANDNANOPARTICLES INPHARMACEUTICALPRODUCTS: DESIGN, MANUFACTURING, BEHAVIOR AND PERFORMANCE Vol.29. Springer, 2018; and Tadros, Tharwat F. BASIC PRINCIPLES OF FORMULATION TYPES Vol.2. Walter de Gruyter GmbH & Co KG, 2018. Non-limiting examples of suitable materials can include a biocompatible natural or artificial polymer such as alginate, cellulose, chitosan, gelatin, polyglycolic acid (PGA), polylactic acid (PLA), or polyethylene glycol (PEG), cationic, anionic and neutral lipids such as cholesterol, Dioleoyl-3- trimethylammonium propane (DOTAP), distearoylphosphatidylcholine (DSPC), 1,2- dioleyloxy-3-dimethylaminopropane (DODMA), N-[1-(2,3-dioleyloxy)propyl]- N,N,N-trimethylammonium chloride (DOTMA), or 1,2-dilinoleyloxy-3-(N,N- dimethyl)aminopropane (DLinDMA), as well as combinations and blends of such polymers and lipids, including structured lipid or polymer-lipid microparticles and nanoparticles. In addition, the fusion protein disclosed herein can be self-assembled with biotinylated polymers and lipids, including single or combination materials in nanoparticles or microparticles, or scaffolds, and which are either biodegradable or non-biodegradable. The pharmaceutical compositions disclosed herein can be included in a container, pack, or dispenser together with instructions for administration. A kit comprising the plasmids encoding the fusion protein disclosed herein (e.g., SA- CXCL12, SA-pr CXCL12, SA-FasL) and instructions for preparing a biotinylated microgel conjugated to the fusion protein for use in the methods disclosed herein isalso contemplated in the present disclosure. Such kits can further include at least onematerial for use in preparing the biotinylated microgel (e.g., PEA macromers, SA and / or avidin moieties). Methods of Use Provided herein are methods of administering a composition comprising a plurality of biotinylated microgels for use in of inducing an immune privileged environment in a subject in need thereof. A “subject in need thereof’ as utilized herein can refer to a subject in need of treatment for a disease or disorder for which the treatment is organ / tissue / cell transplantation. Non-limiting examples of such diseases can include chronic kidney failure, heart failure, valvular heart disease, congenital heart disease, coronary artery disease, cardiomyopathy, cystic fibrosis, pulmonary edema, emphysema, pulmonary hypertension, Type I insulin-dependent diabetes (T1D), congenital liver defects, and short bowel syndrome. In some embodiments, the subject is a human subject. In some embodiments, the subject is a juvenile subject. In some embodiments, the subject is an adult subject. In some embodiments, the subject is female. In some embodiments, the subject is male. In some embodiments, the human subject is between 18 to 45 years of age. In some embodiments, the human subject is between 18 to 65 years of age. In some embodiments, the human subject is over 65 years of age. In some embodiments, the human subject is between 7 to 18 years of age. In some embodiments, the human subject is between 8 to 17 years of age. In some embodiments, a subject is 8-11 years of age. In some embodiments, a subject is between 0-14 years of age. In some embodiments, a subject is 15-39 years of age. Methods herein further comprise transplanting an organ / tissue / cells into a subject. In some embodiments, the subject in need thereof is a transplant recipient. In some embodiments, the subject in need thereof is at risk of needing a transplant. Transplantation is a medical procedure in which an organ / tissue / cell is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ / tissue / cell. In some embodiments, the transplantation is an islet cell transplant, a pancreas transplant, a skin graft, a skin transplant, a bone graft, a bone marrow graft, a bone marrow transplant, a heart transplant, a kidney transplant, a lung transplant, a liver transplant, and / or a vascular-composite allograft. In some embodiments, thetransplantation is an islet cell transplant.In some embodiments, the organ / tissue / cell are procured from a donor. In some embodiments, an organ / tissue / cell is explanted from one subject (the donor), submitted to the materials and methods as described herein, and transplanted into another subject (the recipient). In some embodiments, an organ / tissue / cell is explanted from one subject (the donor), submitted to the materials and methods as described herein, and transplanted into the same subject (the donor and the recipient are one subject). In some embodiments, the donors are human subjects. In some embodiments, the donors are non-human subjects (e.g., xenotransplantation). In some embodiments, the recipients are human subjects in need of a transplant. The donor and recipient can be at the same location, or organs can be transported from a donor site to another location. An allograft is a transplant of an organ or tissue between two genetically non-identical members of the same species. Due to the genetic difference between the organ and the recipient, the recipient's immune system can identify the organ as foreign and attempt to destroy it, causing transplant rejection. In addition, in cases of stem cell, bone marrow or other hematopoietic transplants the immune cells of the transplant attack the host cells. This is called Graft-versus-host disease (GvHD). “Graft” refers to transplanted, or donated tissue, and “host” refers to the tissues of the recipient. In some embodiments, a subject treated according to the methods disclosed herein does not require immunosuppressive treatment after transplantation of the graft. In some embodiments, a subject treated according to the methods disclosed herein does not require immunosuppressive treatment for at least about or about 30 days, 60 days, 180 days, 1 year, or more than 1 year after transplantation of the graft. In some embodiments, a subject treated according to the methods disclosed herein can be weaned off of immunosuppressive treatment after transplantation of the graft. In some embodiments, a subject treated according to the methods disclosed herein can be weaned off of immunosuppressive treatment at least about or about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, or more than 6 months after transplantation of the graft. In some embodiments, a subject treated according to the methods disclosed herein can discontinue immunosuppressive treatment at least about or about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3months, 4 months, 5 months, 6 months, or more than 6 months after transplantation ofthe graft. Provided herein are also methods of treating or preventing graft rejection in a subject in need thereof. Methods provided herein comprise administering an effective amount of a composition disclosed herein comprising a plurality of biotinylated microgels to the subject in need thereof. In some embodiments, the administering occurs before transplantation, at the time of transplantation, after transplantation, or any combination thereof. In some embodiments, an effective amount of a composition disclosed herein is administered to the site of transplantation. In some embodiments, an effective amount of a composition disclosed herein is administered to the site of transplantation at the same time of graft transplantation (e.g., the composition and the graft are co- transplanted). In some embodiments, a graft transplanted according to the methods disclosed herein can be functional (e.g., at least about or about 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% functional) for at least about or about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, or more than 6 months after transplantation of the graft. In some embodiments, a graft transplanted according to the methods disclosed herein can survive for at least about or about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, or more than 6 months after transplantation of the graft. In some embodiments, a graft transplanted according to the methods disclosed herein is an islet allograft. In some embodiments, an islet allograft according to the methods disclosed herein can survive for at least about or about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, or more than 6 months after transplantation of the islet allograft. In some embodiments, an islet allograft according to the methods disclosed herein can be functional (e.g., at least about or about 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% functional) for at least about or about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, or more than 6 months after transplantation of the islet allograft. Functionality of an islet allograft can be assessed according to methods known in the art (see, e.g., Sutherland et al., Transplantation.2008 Dec27;86(12):1799-802; Liu et al., Sci Transl Med. 2025 May 21;17(799):eadj9615),including but not limited to assessing stable insulin and C-peptide secretion. In some embodiments, an islet allograft according to the methods disclosed herein can secrete insulin for at least about or about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, or more than 6 months after transplantation of the islet allograft according to the methods disclosed herein. In some embodiments, plasma C-peptide levels can remain relatively stable (about 200 pM to 700 pM) in the subject after transplantation of the islet allograft according to the methods disclosed herein. In some embodiments, plasma C-peptide levels remain relatively stable in the subject for at least about or about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, or more than 6 months after transplantation of the islet allograft according to the methods disclosed herein. Also provided herein are methods of treating Type 1 Diabetes (T1D) in a subject in need thereof. Methods provided herein comprise administering an effective amount of a composition disclosed herein comprising a plurality of biotinylated microgels to the subject in need thereof. In some embodiments, the administering occurs before islet allotransplantation, at the time of islet allotransplantation, after islet allotransplantation, or any combination thereof. In some embodiments, methods disclosed herein can include administering a therapeutically effective amount of a composition disclosed herein, wherein a therapeutically effective amount of the composition treats, prevents, or attenuates T1D or a symptom thereof. Symptoms of T1D and methods of measuring said symptoms, symptom progression, as well as progression of T1D are generally known in the art and are suitable for use herein (see, e.g., Lucier & Mathias. Type 1 Diabetes. [Updated 2024 Oct 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from ncbi.nlm.nih.gov / books / NBK507713 / - accessed June 2, 2025). In some embodiments, insulin use of a TD1 subject is decreased after treatment according to the methods disclosed herein as compared to baseline. Here, baseline refers to the amount of insulin a TD1 subject was administered before treatment according to the methods disclosed herein. In some embodiments, insulin use is decreased by about or at least 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%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95%, or 100% after treatment according to the methods disclosed herein, as compared to a previous time point, after the end of treatment, or as compared to baseline. In some embodiments, a TD1 subject treated according to the methods described herein does not need to administer insulin after transplantation of the islet allograft according to the methods disclosed herein. In some embodiments, a TD1 subject treated according to the methods described herein does not need to administer insulin for at least about or about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, or more than 6 months after transplantation of the islet allograft according to the methods disclosed herein. In some embodiments, the blood glucose level a TD1 subject is decreased after treatment according to the methods disclosed herein as compared to baseline. Here, baseline refers to the blood glucose level of the TD1 subject before treatment according to the methods disclosed herein. In some embodiments, the blood glucose level of the TD1 subject is decreased by about or at least 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%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% after treatment according to the methods disclosed herein, as compared to a previous time point, after the end of treatment, or as compared to baseline. In some embodiments, a TD1 subject treated according to the methods described herein is normoglycemic (about 70-99 mg / dL) after transplantation of the islet allograft according to the methods disclosed herein. In some embodiments, a TD1 subject treated according to the methods described herein is normoglycemic for at least about or about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, or more than 6 months after transplantation of the islet allograft according to the methods disclosed herein. Additional Embodiments Compositions for use are also disclosed. For example, provided are compositions comprising a plurality of biocompatible polymers and / or a plurality of biotinylated microgels for use in treating or preventing graft rejection in a subject in need thereof. Also disclosed are compositions comprising a plurality of biocompatiblepolymers and / or a plurality of biotinylated microgels for use in inducing an immuneprivileged environment in a subject in need thereof. In some instances, disclosed are compositions comprising a plurality of biocompatible polymers and / or a plurality of biotinylated microgels for use in inducing a graft vascularization in a subject in need thereof. The compositions for use include at least one fusion protein comprising a protease-resistant C-X-C motif chemokine 12 (CXCL12) polypeptide fused to a first streptavidin moiety or first avidin moiety; and at least one fusion protein comprising a Fas ligand (FasL) polypeptide fused to a second streptavidin moiety or second avidin moiety. The compositions for use herein incorporate the biocompatible polymers, including microgels and biotinylated microgels discussed in this application. In some instances, disclosed are uses of compositions comprising biocompatible polymers having at least one fusion protein comprising a protease- resistant C-X-C motif chemokine 12 (CXCL12) polypeptide; and at least one fusion protein comprising a Fas ligand (FasL) polypeptide. Also disclosed are uses of any one of the compositions (e.g., biocompatible polymers; e.g., microgels) in the manufacture of a medicament for the treatment or prevention of graft rejection in a subject in need thereof. In some embodiments, disclosed are uses of any one of the compositions (e.g., biocompatible polymers; e.g., microgels) in the manufacture of a medicament for inducing an immune privileged environment in a subject in need thereof. Finally, provided herein are uses of any one of the compositions (e.g., biocompatible polymers; e.g., microgels) in the manufacture of a medicament for inducing a graft vascularization in a subject in need thereof EXAMPLES The invention is further described in the following examples, which do not limit the scope of the invention described in the claims. Materials and Methods The following materials and methods were used in the Examples below. Animals Donor BALB / c and recipient C57BL / 6 mice (8-week-old male, 23-25 g) were purchased from Jackson Laboratories (Bar Harbor, ME). Pancreatic islets were harvested from 8–week-old BALB / c using a standard gradient-based protocol as previously described40,41. Diabetes induction and management Diabetes was induced in animals by a single intraperitoneal injection of freshly dissolved streptozotocin (STZ) in sodium citrate buffer (pH 4.4-4.6) and the STZ dose was calculated based on the body weight of each animal, with a final dose of 200 mg / kg. Diabetes was confirmed by two consecutive blood glucose readings exceeding 250 mg / dL. Blood glucose levels were monitored daily via tail bleeding using EvenCare G2 Blood Glucose Meters (Medline, Northfield, IL, USA). Post-transplant graft rejection and a return to the diabetic state was defined as blood glucose of above 250 mg / dl, based on blood glucose readings taken on two consecutive days. Exogenous insulin (Humulin R, Lilly, Indianapolis, IN, USA) was administered to animals with high blood glucose to maintain normoglycemic levels below 250 mg / dl, either prior to transplant or following graft rejection as needed. Production of SA-CXCL12, SA-prCXCL12 and SA-FasL protein products Prepared herein were fusion proteins that were comprised of a modified form of core streptavidin (SA) (SEQ ID NO: 7) and either CXCL12 (SEQ ID NO: 1) or protease-resistant CXCL12 (SA-prCXCL12) (SEQ ID NO: 2). The SA C terminus was joined to the N terminus of the CXCL12 or prCXCL12 using a flexible serine- glycine linker such that, when the fusion protein was self-assembled with biotin on the surface of the microgel, the binding and signaling domain (optionally with the protease resistant modification) was exposed to the outside. Also prepared was a fusion protein comprising a modified form of core streptavidin (SA) (SEQ ID NO: 7) and a modified form of FasL that includes only the extracellular domain (SEQ ID NO: 15). Similarly, the SA C terminus was joined to the N terminus of the FasL protein using a flexible serine-glycine linker. The SA-FasL, SA-CXCL12 and SA-prCXCL12 proteins were produced using a Drosophila Expression System expression system using previous protocols42,43. PMT / BiP / V5 inducible expression vector (Invitrogen) was used to transfect Drosophila cells for SA-CXCL12, SA-prCXCL12 and SA-FasL. Stable transfected cells were induced for protein expression for 2 or 3 days. Protein was purified usingNi-affinity columns (QIAGEN, Valencia, CA) and protein bioactivity was validatedas previously described16,19and characterized for purity and structure using SDS- PAGE, and Western blots utilizing Rabbit anti-CXCL12 / SDF1 (Cell Signaling Technologies, clone D32F9, Danvers, MA, USA) and IRDye® 680RD Goat anti- Rabbit IgG Secondary Antibody (Licorbio, Lincoln, NE, USA). Validation of SA-CXCL12 and SA-prCXCL12 bioactivity Bioactivity of SA-CXCL12 and SA-prCXCL12 as both a chemotactic and fugetactic agent was validated through a previously designed transmigration assay44,45(see FIG.4I) using purified CD3+ T cells exposed to different concentrations of SA- prCXCL12 in vitro. At a higher concentration, CXCL12 exhibited fugetactic activity, causing T cells to migrate away, while at a lower concentration, CXCL12 acted as a chemoattractant, promoting T cell migration toward the source. AMD3100 functioned by disrupting the binding of CXCL12 to its receptor, CXCR4, thereby inhibiting both chemotaxis and fugetaxis. To abrogate the activity of CXCL12, CD3+ T cells (human PBMC and mouse splenocytes) in the top chamber were pretreated with AMD3100 (CXCR4 antagonist as a control group, 200 nM) (Selleck Chemicals, Houston, TX, USA) for 30 minutes at 37°C. In the chemotaxis assay, CXCL12 protein was added to the lower chamber of a transwell system to attract T cells, allowing them to migrate toward the CXCL12 gradient. In contrast, for the fugetaxis assay, CXCL12 was added to the upper chamber, creating a gradient that repelled T cells from the upper chamber to the lower chamber. Plates were incubated for 3 hours at 37°C, then, cells migrating into the lower chamber were counted using a hemocytometer and trypan blue. Validation of SA-prCXCL12 and SA-FasL binding to microgels Polyethylene glycol-4-maleimide (PEG4-MAL) biotinylated microgels were generated as previously described18,20. Biotinylated microgels with a defined size and composition (150–200 μm in diameter) were used to capture and present SA-FasL and SA-CXCL12 / SA-prCXCL12 through their SA domain19. Microgels were quantified by manual counting under a standard light microscope at 4x magnification. Successful engineering of microgels with SA-FasL, SA-CXCL12 and SA- prCXCL12 fusion proteins was confirmed by fluorescence imaging. A total of 1000 microgels were incubated for 2 hours on a rotator with 1000 ng of SA-FasL and SA-CXCL12 / SA-prCXCL12 in 500 μl PBS. Siliconized 1.5 ml tubes were used formicrogels. Afterwards, the protein engineered microgels were stained with anti–SA- Dylight488 to detect the proteins and SA-PE dye at room temperature for 12 minutes following 17 minutes at 4°C on rotator (cold room) in PBS, then microgels were washed with PBS by centrifuging at 350 g for 5 minutes (Vector laboratories, Shirley, MA) to visualize microgel with fluorescence microscopy at 10x magnification. Image analysis was performed to verify binding of proteins to the microgels. Unmodified microgels (without SA-FasL or SA-CXCL12 / SA-prCXCL12) were used as controls for background staining. Demonstration of the in vitro stability and the release kinetics of SA- prCXCL12 and SA-CXCL12 The in vitro release of protein from the microgel was evaluated by incubating SA-prCXCL12 or CXCL12 (1000 ng) with 1000 microgels. After modification of microgel with protein and subsequent washing steps by centrifuging at 350 g for 5 minutes (min), the supernatant was collected at various time points for each sample (0, 4 hours (h), 6 h, 8 h, 1 day, 2 days, and 3 days post-engineering) to detect the released protein in the supernatant at room temperature. Human CXCL12 / SDF-1 alpha ELISA (R&D Systems, Minneapolis, MN, USA) and Western Blot methods were used to measure the release of proteins. The MATLAB Image Processing Toolbox was utilized for the quantitative analysis of Western blot bands. Release of CXCL12 without SA was detected using DyLight 488-tagged anti-CXCL12 (FIG. 2B). Standard curves of CXCL12α-DyLight488 (ranging from 40 nM to 0) were generated in triplicate on each plate. Data were averaged across technical triplicates, and error bars represented the standard deviation of four independent experimental replicates. Fluorescence at 488 nm was measured with a BioTek Synergy H3 plate reader (Vermont, USA) using costar 96-well black, opaque-bottom plates (n=4). Islet functionality assay Islet isolation and culturing procedures were optimized for transplant surgery. Isolated islets were cultured in a gas permeable Grex flasks (Wilson Wolf, New Brighton, MN, USA). The effect of SA-prCXCL12 protein (1 μg and 100 ng) on islet functionality was evaluated on handpicked islets using glucose-stimulated insulin / C peptide secretion (GSIS) assay, as previously described26. Briefly, islets incubatedfor 24, 48, or 72 hours at 37°C in a cell culture incubator were subjected to starvationconditions in a KREBS buffer (Krebs-Ringer Bicarbonate Solution) solution containing 1.67 mM glucose for one hour. Subsequently, the islets were exposed to a low glucose concentration of 2 mM for 30 minutes, followed by stimulation with a high glucose solution of 20 mM. At each phase of stimulation, supernatant samples were collected to quantify release of insulin and C-peptide secretion, an indicator of insulin release. C-peptide or insulin levels were measured using mouse C-Peptide or ultra-sensitive insulin ELISA kits (Crystal Chem, IL, USA). Statistical analyses were performed two-way ANOVA-Graphpad (Dotmatics, Boston, MA, USA) to evaluate significant differences between low and high glucose phases and across the time points, with a p-value < 0.05 considered significant. Transplantation surgery and diabetes monitoring Islets were prepared from BALB / c donors using a standard isolation protocol40,41. A total of 2400 engineered microgels and 1200 BALB / c islets were co- transplanted into the epididymal fat pad (EFP) of streptozotocin (STZ)-induced diabetic C57BL / 6 recipients43,46(FIGS.13A-13B). Diabetic animals (n=10) received either islets with unmodified microgel or islets combined with SA-FasL and / or SA-CXCL12 / SA-prCXCL12-presenting microgels. Animals were monitored for blood glucose levels twice a week for 180 days. Intraperitoneal Glucose Tolerance Test (IPGTT) The glucose response of long-term survival animals was assessed at day 90. Long-term survival is defined as the maintenance of normoglycemia in animals after transplant, with BG level below 250 mg / dL. At 4-weeks and 12-weeks post transplantation, mice were fasted for 6 hours and subjected to IPGTT via intraperitoneal glucose (2 g / kg body weight) injection. A glucose solution was prepared by dissolving 0.4 g of glucose in 2 mL of saline. Each animal received an injection of the glucose solution adjusted to their body weight (e.g., a 25 g animal received 250 µL of the solution). Blood glucose levels were measured before glucose injection and at 15, 30-, 60-, 90-, and 120-minutes post-injection. At the endpoint of the IPGTT, serum samples were collected via retroorbital bleed and immediately frozen at −80°C for subsequent analysis. Insulin or C-peptide levels were measured by ELISA as described above. Immunoprofiling with flow cytometryMononuclear cells from spleens and lymph nodes (LN) from transplant recipient animals were harvested and characterized using an optimized flow cytometry panel of anti-mouse CD45-AF488, CD3-pacific blue, CD4-Spark plus UV395, CD8-BV785, CD25-BV650, CXCR4-BV711, TNFα-BV421, IFN-γ- PE / Dazzle594, IL-2-Spark-red718, FoxP3-PE, IL-10-AF647, CD69-PE / Cy5, CD68- BV605, CD163-PE / Cye7 (Biolegend, San Diego, CA, USA) and CD127-BUV737, CD86-BUV563 (BD Biosciences, Bedford, MA, USA) (see Table 1). Table 1: Optimized Flow Cytometry Panel Single-cell suspensions from spleens and LN were surface-stained, fixed, permeabilized, and intracellularly stained before data acquisition on an Aurora™ flow cytometer (Cytek Biosciences, Bethesda, MD, USA). Data analysis was performed with FlowJo (BD Life Sciences, Ashland, OR, USA) and OMIQ (Dotmatics, Boston, MA, USA) software. To evaluate antigen-specific responses, lymph node (LN) and spleen cells (n=3) were stimulated for 6- and 12-hours at 37°C in a cell culture incubator with BALB / c islet antigens (sonicated 80 islets per well) or pooled islet antigen peptides (10 μg / ml concentration). Positive control stimulation was performed by 6-hours incubation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. Table 2 provides the islet antigen peptides which were custom synthesized for use herein (Aapptec, Louisville, KY, USA). The C-terminal of the peptides were synthesized as an amide to neutralize negative charge created by the C-terminal COOH. Table 2: Islet Antigen Peptides Immunohistochemistry Islet grafts, pancreas, and surrounding tissues were fixed with 10% zinc formalin, 5 μm sections were cut. FFPE tissue sections were baked for 30 minutes at 60°C and deparaffinized (Leica AR9222) prior to staining. Immunofluorescent staining was performed on the Leica Bond RX automated staining platform using the Leica Biosystems Refine Detection Kit (Leica DS9800). Tissues were stained using antibodies against mouse CD3 (clone D4V8L), CD8 (clone D4W2Z), F4 / 80 (clone D2S9R), CD31 (clone D8V9E), CD4 (clone D7D2Z), FoxP3 (clone D6O8R), glucagon (clone D16G10), and insulin (polyclonal)(Cell Signaling Technology, Danvers, MA, USA). Immunofluorescence staining was performed using two panels: first panel included markers for insulin, CD31, FOXP3, and CD4, while second panel targeted glucagon, F4 / 80, CD3, and CD8. Following staining, slides were counterstained with DAPI (Nucblue; Invitrogen R37606) and coverslipped (Prolong Diamond; Invitrogen P36961, Thermo Fisher Scientific, Carlsbad, CA, USA). Stained sections (n=3 biological replicates with n=2 technical replicates) were examined and scanned with Ventana multicolor imaging system (Roche, Boston, MA, USA), with images captured for quantitative analysis of immune cell infiltration, islet integrity, and insulitis (inflammation of the islets). Data from IHC (quantified using ImageJ software) were examined for statistical differences between control and experimental groups. Mixed Lymphocyte Reaction (MLR) Assay T cells were isolated from animals that received the combination treatment (islets combined with SA-FasL and / or SA-prCXCL12-presenting microgels) and the microgel (n = 3 biological replicates per group, with two technical replicates per animal, resulting in a total of n = 6 for each treatment group). Spleens were processed into single-cell suspensions, and a mouse T cell isolation kit was used to enrich T cells in responder splenocytes (combination treatment group (islets with SA-FasL and SA-prCXCL12, long-term survival animals) and the microgel only group). T cells from responder splenocytes (2 × 10⁶ cells) were labeled with 1 µM carboxyfluorescein succinimidyl ester (CFSE) cell trace dye (Thermofisher, Waltham, MA, USA) to label cells in order to track cell division and proliferation, and then the cells were resuspended in compete RPMI medium. CFSE labeled responder cells were collected, washed twice, before co-cultured in 96-well U-bottom plates (1.5 × 10⁵ cells / well) with the same number of irradiated (3000 cGy) splenocytes isolated from BALB / c, C57BL / 6 or C3H third-party mice (1.5 × 10⁵ cells / well). These irradiated BALB / c donor, C57BL / 6 or C3H third-party splenocytes (2 × 106cells) were labelled with 1 µM cell tracer violet dye (Thermofisher, Waltham, MA, USA) before culture with responder cells in 96 well U-bottom plate. After 5 days, cells were stained with fluorochrome-labeled antibodies targeting CD45-BV650, CD3-AF647, CD4-Spark plus UV395, CD8-BV785, CD69-PE / Cye5, TNFα-BV421, IFN-γ-PE / Dazzle594, IL- 2-Spark-red718, and analyzed by flow cytometry. Irradiated cells labelled with violet were negatively gated from flow analysis. Survival of allogeneic and third-party skin grafts in allo-islet transplant recipients Long term survival C57BL / 6 transplant recipients (SA-prCXCL12 plus SA- FasL combination treatment, 180 days survival) were selected and transplanted with BALB / c donor, C57BL / 6 or C3H third-party skin grafts (tail skin harvested from donor mice) onto the dorsal (back) region of the recipient mice24. Graft survival was monitored for more than a month to evaluate any systemic immune tolerance and protective effects conferred by the SA-prCXCL12 and SA-FasL-engineered microgel treatment (n=4). Statistical analysis Unless otherwise indicated, statistical analysis was performed using GraphPad Prism v10.3.1 using unpaired t-tests or two-way ANOVA-Graphpad (Dotmatics, Boston, MA, USA) with significance thresholds set as follows: * p<0.05, ** p<0.01, and *** p<0.001. Example 1: SA-CXCL12 and SA-prCXCL12 protein production and validation with Western blot analysis. We designed two constructs: one with a FLAG tag (SEQ ID NO: 17) and the other with a His tag (SEQ ID NO: 18) in a PMT / BiP / V5-HisA CuSO4-inducible expression vector (Invitrogen) where the C terminus of the tags were joined to the N terminus of the SA. These constructs were transfected into Drosophila cells for induced expression. The FLAG construct produced significantly higher amounts of protein. As such, we proceeded with this construct for protein production. Stable transfected cells were induced for protein expression for 2 or 3 days. Protein was purified using affinity columns. Proteins (SA-CXCL12 and SA- prCXCL12) were characterized for purity and structure using Western blots (FIG. 1A). The tetrameric structure and verification of the SA-CXCL12 protein was assessed under heat treatment and room temperature, and different protein concentrations were also tested using CXCL12-specific antibody (FIG.1B). Example 2 : Validation of SA-CXCL12 and SA-prCXCL12 bioactivity using a cell-based migration assay. CXCL12 is a chemokine that plays a crucial role in directing the migration of T cells and other immune cells. The migration of T cells in response to CXCL12 can vary depending on its concentration. High doses of CXCL12 can act as achemorepellent for lymphocytes. Movement away from stimuli is CXCR4 receptorand Gai signaling dependent.44,47,48. The bioactivity of the SA-CXCL12 and SA- prCXCL12 proteins was evaluated using an established chemotaxis (chemoattraction) and fugetaxis (chemorepulsion) assay of the response of purified CD3+ T cells to different doses of protein in vitro44,45. In this assay SA-CXCL12 and SA-prCXCL12 exhibited dose-dependent chemotactic or chemorepellent activity for murine splenocytes and primary CD3+T cells from human PBMC in vitro. At a concentration of 1 µg / ml (42.7 nM), SA-CXCL12 and SA-prCXCL12 demonstrated a fugetactic effect on T cells, a key function of the protein that has the potential to immune isolate the transplanted islets (FIGS.4A-4H). SA-prCXCL12 induced a stronger fugetactic response than SA-CXCL12 in both splenocytes and CD3⁺ T cells (FIGS.4C-4D versus FIGS. 4G-4H). The bioactivity of SA-FasL has been previously published and well-established19. Example 3: Validation of SA-CXCL12 and SA-FasL binding to microgels. Hydrogel microparticles (microgels) were synthesized from maleimide- terminated four-arm poly(ethylene) glycol (PEG-4MAL) macromers using microfluidics polymerization to generate microgels of defined size (150-200 μm) and composition in a high throughput fashion. After the protein engineering with microgel, fluorescence imaging was conducted on microgels modified with SA- CXCL12, SA-prCXCL12 and SA-FasL proteins. The co-localization of the anti-SA protein dye with the microgel-SA dye confirmed the successful binding of the proteins to the microgel after the engineering process (FIG.10). Example 4: SA-CXCL12 protein release kinetics from microgels after engineering. Following the validation of SA-CXCL12 binding to the microgel, we characterized its release kinetics. To assess the release dynamics, two complementary techniques were employed: Western blotting to detect the engineered protein and ELISA to quantitatively track its release over time. At the conclusion of the SA- CXCL12 assembly onto the microgel, Western blot analysis revealed that 14.7% of the protein remained in the supernatant while 85.3% was retained within the microgel matrix (FIG.2A). Microgels loaded with CXCL12 alone, without SA, exhibitedminimal release over a 48-hour period, with cumulative release measuring less than0.1 fmol. (FIG.2B). This limited release was anticipated, as the absence of SA, CXCL12 would not bind effectively to the biotinylated microgels, resulting in negligible protein binding and subsequent release. This experiment was used to show the necessity of using an SA-CXCL12 conjugate to achieve effective localization of the protein on the biotinylated microgels. CXCL12 ELISA data showed a substantial loss of SA-CXCL12 detection within 24 hours (FIG.3A) contrary to the expected release from the microgel, indicating the need for a more stable protein formulation. Subsequently, a protein release kinetics assay was also performed using SA-prCXCL12 which was also detectable with this ELISA. The supernatants from each time points were collected after the microgel engineering with SA-prCXCL12 protein. An ELISA was conducted to quantify the amount of protein released in vitro. A rapid release of SA-prCXCL12 was observed at 6 hours post microgel engineering, exceeding the levels detected at other time points. No protein loss was observed throughout the 72 hours incubation time. Between 6 and 24 hours, a slower release kinetic was observed and SA- prCXCL12 demonstrating increased stability compared to CXCL12 (FIG.3B). These findings prompted us to explore the use of SA-prCXCL12 in an allo-islet transplant setting in addition to SA-CXCL12. Example 5: Effect of SA-prCXCL12 on islet functionality ex vivo. SA-prCXCL12 was tested for direct effects on islet function using an ex vivo GSIS assay, as previously described26. Isolated islets were responsive to glucose stimulation and secreted C-peptide over 72 h (FIG.5A). Cultured islets were incubated with varying concentrations of SA-prCXCL12 protein (1 μg and 100 ng) and the impact of the protein on islet functionality was measured. The functionality of the islets remained consistent across all conditions, irrespective of the presence or concentration of SA-prCXCL12 (FIG.5B)26. This was consistent with previously published findings that CXCL12 does not impact islet function or viability23. Example 6: Survival allogeneic islet grafts co-transplanted with SA-FasL and / or SA-CXCL12 or SA-prCXCL12 presenting microgels without systemic immune suppression. We demonstrated successful delivery of CXCL12, prCXCL12 and FasL fusedwith SA and incorporated into biotin coated microgels mixed with allogeneic islets in immunocompetent C57BL / 6 diabetic mice. Engineered microgels and BALB / c islets were co-transplanted into the EFP of diabetic immunocompetent C57BL / 6 recipients without systemic immune suppression. Animals that received either single agent SA- CXCL12 or SA-FasL microgel with allo-islets exhibited approximately 2 weeks of survival. However, when the two microgels were combined and co-transplanted with BALB / c islets, survival was extended to up to one month (p < 0.01), without the need for systemic immune suppression. These results fell short of the previous survival results observed in the CXCL12-alginate model, which demonstrated prolonged survival (>150 days) of human stem cell-derived beta cells without systemic immunosuppression in immunocompetent C57BL / 6 mice26. As noted above, we observed that the degradation of CXCL12 protein in vitro was more pronounced in the microgel formulation, suggesting that protein stability and in vivo exposure might be a key factor in the shorter survival observed in the initial studies using the microgel platform. We hypothesized that using SA-prCXCL12 might help overcome this challenge. We observed a significant and accelerated reduction in hyperglycemia around day 55 in diabetic C57BL / 6 recipients implanted with SA-prCXCL12 microgels and BALB / c islets (n=10, p<0.001) compared to unmodified microgels with islets alone (microgel + islets, n=10) (FIG.6A). We also demonstrated that SA- prCXCL12 and SA-FasL microgels, when combined with allogeneic BALB / c islets, achieved long-term diabetes reversal (n=10, p<0.001) compared to unmodified microgels with islets alone (FIG.6A). Mice treated with the combination of SA- prCXCL12 and SA-FasL achieved long-term allograft survival and maintained optimal glycemic control for over six months (FIG.6B). Furthermore, removal of the EFP graft from a subgroup of these mice after 6 months post-transplantation resulted in hyperglycemia in this group (n=3), indicating that the grafted allo-islets were functional and actively contributing to glycemic control. This observation suggested that the allo-islets within the graft were functional but also potentially protected from immune attack, supporting the hypothesis of immunoprotection within the graft environment. Example 7: Function of allogeneic islet grafts co-transplanted with SA-FasL and / or SA-CXCL12 or SA-prCXCL12 presenting microgels. Next, we evaluated the functional capacity of the transplanted islets with combination treatment, an IPGTT was performed at 4- and 12-weeks post- transplantation (FIG.6C). The IPGTT results demonstrated that glucose response in three transplanted animals with combination therapy (M1, M2 and M3) was comparable to three healthy controls non-diabetic animals (C1, C2, C3), indicating successful engraftment and functional integration of the transplanted islets (FIG.6C). Sera from transplanted mice were also used to evaluate insulin secretion after the IPGTT test. Mice treated with a combination of SA-prCXCL12 and SA-FasL demonstrated a significantly higher insulin levels compared to those transplanted with non-engineered microgels and islets (FIG.5C). Notably, the insulin levels in the combination treatment group were comparable to those in healthy, non-diabetic control mice. These findings suggested that the comparable insulin level in serum samples from transplanted animals were attributable to the functional insulin- secreting islets, which were effectively protected by the microgel engineered with the therapeutic proteins. The concentration of CXCL12 protein was quantified in the serum of transplanted mice post-transplantation to investigate the presence of the protein in the systemic circulation 15-30 days post-surgery. Serum from mice (n=3) transplanted with unmodified microgels and islets served as a negative control. Comparative analysis between this control group and mice transplanted with SA-prCXCL12 microgel, either alone or in combination with SA-FasL, showed no significant difference in protein levels in serum samples (FIG.5D). Example 8: Localized immune tolerance to skin transplants in recipients of allo- islets with microgels containing SA-prCXCL12 and SA-FasL. C57BL / 6 recipients of allo-islets and microgels containing SA-prCXCL12 and SA-FasL were transplanted with BALB / c donor, C57BL / 6 and C3H third-party skin grafts at 180 days post islet transplant. Graft survival was monitored to evaluate thelocal versus systemic immune tolerance and protective effects conferred by the SA-prCXCL12 and SA-FasL-engineered microgel treatment. Both donor and third-party skin grafts were acutely rejected (~11 days), indicating that localized immune isolation of the allo-islet graft was induced in an anatomic site-specific manner in these mice (FIG.6D). Example 9: A time matched study of immune profiling by flow cytometry. Immune protection achieved with the combination treatment of SA- prCXCL12 and SA-FasL delivery was further investigated using immunohistochemical (IHC) and flow cytometric assays to analyze anti-allo humoral and cell-mediated immunity. Comprehensive immune profiling was conducted to assess the presence of CD4+ T cells, Tregs, CD8+ Teff cells, and macrophages in both experimental and control groups two weeks post-transplantation. The percentage of CD3+, CD4+, and CD8+ populations did not show a significant change between treatment groups (combination (SA-FasL and SA-prCXCL12) versus microgel) in the LN or spleen (FIGS.7A and 11A-11C), with the exception of higher percentage of CD8+ population observed in the spleen samples of the microgel group compared to the combination treatment group (p<0.01). LN samples from animals receiving the unmodified microgel (microgel group – FIGS.11A-11C) with islets demonstrated consistent high expression of the CD69 activation marker in both CD4+ and CD8+ T cell populations (p<0.001) compared to combination treatment group. The percent of CD4+ T cells from the microgel group also demonstrated higher CXCR4+ expression in both spleen and LN (p<0.001). Additionally, increased expression of the pro- inflammatory cytokine IFN-γ was observed in CD8+ cells from LN and spleen samples in the unmodified microgel group (p<0.001), as well as a higher prevalence of pro-inflammatory IFN-γ+ macrophages was noted in spleen samples (FIGS.7A and 11A-11C, p<0.01). Overall, the microgel group exhibited a more inflammatory immune profile compared to the combination (SA-prCXCL12 and SA-FasL) or SA- prCXCL12 treatment group alone based on the percentage of populations. AS such, the data suggested that the treatment could exert an immune modulatory effect and influence T cell and macrophage responses to the allo-islet graft. Detailed phenotyping of immune cells in the LN and spleen was performed using PMA / ionomycin stimulation, BALB / c islet antigens, and pooled islet antigenpeptides. We evaluated the immune response to BALB / c islet antigens and pooledislet antigen peptides in animals treated with combination therapy (SA-prCXCL12 + FasL), SA-prCXCL12, or microgel (control) by analyzing spleen and lymph node samples at 6- and 12-hours after stimulation. PMA / ionomycin stimulation was performed at the 6-hour time point as an internal positive control. BALB / c islet antigens were obtained from BALB / c frozen islets and demonstrated comparable responses to custom synthesized pooled islet antigen peptides in immune stimulation experiments. Both BALB / c islet antigens and pooled islet antigen peptides were found to increase CXCR4 expression in CD4+ and CD8+ T cells at the 12-hour time point in both LN and spleen in the microgel group compared to the combination (SA- prCXCL12 + SA-FasL) treatment group at the 12-hour time point (p<0.05-p<0.001, FIGS.7B, 12A, 12B). Additionally, the CD8+IFN-γ+ T cells were higher in the microgel group compared to the combination treatment group at both the 6- and 12- hour time points after BALB / c islet antigens and pooled islet antigen peptides stimulation, similar to the unstimulated samples (p < 0.05 to p < 0.001, FIGS.7B, 12A, 12B). BALB / c islet antigens and pooled islet antigen peptides were found to increase IL-2 expression in CD8+ T cells at the 12-hour time point in the spleen, with higher levels observed in the microgel group compared to the combination treatment group (p < 0.05 to p < 0.001, FIGS.7B, 12A, 12B). Interestingly, CD4+CXCR4+FOXP3+ T cells were significantly higher in the combination treatment group compared to the microgel group at the 12-hour time point in the spleen. In contrast, the CD4+CXCR4+ cell population was higher in the microgel group compared to the combination treatment group at the 12-hour time point in both the spleen and LN after BALB / c islet antigens and pooled islet antigen peptides stimulation, similar to the unstimulated samples (p < 0.05 to p < 0.001, FIGS.7B, 12A, 12B). PMA / Ionomycin stimulation, used as an internal positive control, demonstrated the expected increase in IFN-γ, IL-2, and the activation marker CD69 in this group. Example 10: A time matched study of IHC staining of the EFP graft. There was enhanced vascularization as evidenced by increased numbers of CD31+ cells at the EFP graft site, and Treg cells (FoxP3 positive cells) were present in significantly higher numbers in animals treated with the modified microgels (SA-prCXCL12 + SA-FasL) compared to those in the control group, which receivedunmodified microgels. Lastly, we observed increased numbers of CD8+ cells and C68+ macrophages in grafts transplanted with islets and unmodified microgels compared to combination treatment group (FIG.8). Example 11: Allograft tolerance was associated with hypoproliferation of donor- specific CD8+ T cells and reduced expression of IFN-γ and IL-2. We further investigated the mechanism of tolerance in the combination group using an MLR assay. A reduced proliferative response of donor-reactive CD8+ T cells was observed in graft recipients treated with the combination therapy compared to the microgels only group (FIG.9). These findings indicated that allograft tolerance in the combination group was associated with donor-specific T cell hypoproliferation and decreased expression of IFN-γ and IL-2 cytokines in the CD8 T cells (FIG.9). This suggested a state of reduced responsiveness to donor antigens or the establishment of localized anatomic site-specific immune privilege or immune isolation when SA- prCXCL12 and SA-FasL were co-delivered with the allo-islets. Example 12: Long term study of SA-prCXCL12 + / - SA-FasL microgel formulation in diabetic NOD / LtJ mice. Islets derived from healthy non-diabetic BALB / c mice are mixed with the optimal microgel formulation as described above and transplanted into the epididymal fat pad of spontaneously diabetic female NOD / LtJ mice (BG ≥ 300 mg / ml)(Jackson Laboratory). Treatment groups (n=10 per group) include donor islets with (1) no microgels (negative control); (2) microgels without bound protein; (3) microgels alone with bound protein (prCXCL12 + / - FasL) (optimal dose of protein per graft); and (4) suboptimal 10% of optimal dose of SA-protein microgel (0.2 mg per graft per protein). Graft function is monitored via assessment of blood glucose, levels of serum murine C-peptide and glucagon and fasting IPGTTs at day 60, 90 and 180 post transplantation in a subgroup of long-term survivors in the treatment group. Reversal of diabetes is defined as blood glucose readings <250 mg / dl upon commencement of treatment and graft failure is defined as blood glucose >250 mg / dl on two consecutive readings up to 180 days post-transplant. Upon graft recovery at explantation, paraffin- embedded sections of the islet graft are subjected to immunohistochemistry for C-peptide / insulin, glucagon, CD3, CD45 and FoxP3 immune staining and quantitation of beta cells, CD8+ or Fox P3+T cells by image analysis according to methods previously described52,56. Assays of NOD / LtJ and human islet cell function in vitro pre transplantation and ex vivo post-explantation. Viability of murine alloislets pre-transplantation and post-explantation are measured by FDA / PI staining. At these same time points, islet cell subset analysis is performed using IHC staining and flow cytometry as previously described52, 53, 56. Briefly, the alloislets are fixed in 4% PFA followed by ethanol dehydration. Samples are embedded in paraffin followed by 4-µm sectioning. These sections are deparaffinized, rehydrated and processed for appropriate antigen retrieval and then stained with insulin, glucagon, somatostatin and CXCL12-specific antibodies for 1-hr at 37°C. Following a brief wash, sections are incubated with fluorescently-labeled secondary antibodies for an hour at 37°C. The cells are counterstained with DAPI and the labelled sections are analyzed on a fluorescent microscope for percent (%) insulin, glucagon and somatostatin positive cells. CXCL12 content of the capsules pre-transplant and post-explant is measured by LC / MS assay. Glucose stimulated insulin release (GSIR) is measured in vitro using perfusion device (BioRep) as previously described52,56. A GSIS value of ≥ 2 is considered a positive response. GSIS of ILC is carefully evaluated to determine the potency of the alloislet over time. Immunogenicity and immunohistochemistry assays. In all NOD / LtJ mice, explanted islets, pancreas and surrounding tissues are frozen or fixed, sectioned and stained for IgG and complement components (C3) as well as infiltrating macrophages and T cells using IHC staining for CD3, CD4, CD8, CD25, F4 / 80 or CD68, CD163 and FoxP3 as well as c-peptide and insulin as previously described52,56. The mechanisms of tolerance in the experimental groups are examined using established mixed lymphocyte reaction (MLR) assays, flow cytometry, and skin graft experiments. Proliferative response of donor-reactive CD8+, CD4+ T cells is examined with a MLR assay. Immune cell profile in LN and spleen is assessed using our optimized flow panel for specific markers to CD45, CD3, CD4, CD8, CD25,CD127, and CXCR4, in conjunction with intracellular staining for TNFα, IFN-γ, IL-2,FoxP3, IL-10, and activation markers CD69, Ki-67, and macrophage markers CD68, CD86, and CD163 to quantitate activation markers, Teffs, Tregs and M1 (pro- inflammatory) , M2 (anti-inflammatory) macrophage cell populations. Peripheral blood anti-murine is quantitated on a monthly basis from NOD / LtJ recipients of murine islets. In addition, allogeneic and 3rdparty skin grafts is performed on a subgroup (n = 5) of long-term surviving alloislet recipients. Additionally, the grafts and serum samples are evaluated for FasL and CXCL12 presence at graft at day 7 and day 180 post-retrieval using commercially available ELISA assays. References 1. 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Pharmacology and Therapeutics vol.19363–74 Preprint at https: / / doi.org / 10.1016 / j.pharmthera.2018.08.011 (2019). 26. Alagpulinsa, D. A. et al. Alginate-microencapsulation of human stem cell–derived β cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression. American Journal of Transplantation 19, 1930–1940 (2019). 27. Sremac, M. et al. Short-term function and immune-protection of microencapsulated adult porcine islets with alginate incorporating CXCL12 in healthy and diabetic non-human primates without systemic immune suppression: A pilot study. Xenotransplantation 30, e12826 (2023). 28. Alagpulinsa, D. A. et al.209.6: Long-term Functional Survival of Human Stem Cell- derived Islets Microencapsulated in Alginate With CXCL12 in Non-human Primates Without Immunosuppression. Transplantation 105, S16–S16 (2021). 29. Leng, Q., Nie, Y., Zou, Y. & Chen, J. Elevated CXCL12 expression in the bone marrow of NOD mice is associated with altered T cell and stem cell trafficking and diabetes development. BMC Immunol 9, 51 (2008). 30. Ara, T., Tokoyoda, K., Okamoto, R., Koni, P. A. & Nagasawa, T. The role of CXCL12 in the organ-specific process of artery formation. Blood 105, 3155–3161 (2005). 31. Chen, T. et al. Alginate encapsulant incorporating CXCL12 supports long-term allo- and xenoislet transplantation without systemic immune suppression. American Journal of Transplantation 15, 618–627 (2015). 32. Papeta, N. et al. Long-term survival of transplanted allogeneic cells engineered to express a T cell chemorepellent. Transplantation 83, 174–183 (2007). 33. Liu, Z. & Habener, J. F. Stromal cell-derived factor-1 promotes survival of pancreatic beta cells by the stabilisation of beta-catenin and activation of transcription factor 7-like 2 (TCF7L2). Diabetologia 52, 1589–1598 (2009). 34. Jin, D. K. et al. Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nature Medicine 200612:512, 557–567 (2006). 35. McCandless, E. E., Wang, Q., Woerner, B. M., Harper, J. M. & Klein, R. S. CXCL12 Limits Inflammation by Localizing Mononuclear Infiltrates to the Perivascular Space during Experimental Autoimmune Encephalomyelitis. The Journal of Immunology 177, 8053–8064 (2006). 36. Sremac, M. et al. Preliminary Studies of the Impact of CXCL12 on the Foreign Body Reaction to Pancreatic Islets Microencapsulated in Alginate in Nonhuman Primates. Transplant Direct 5, (2019). 37. Lobmann, R. et al. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients. Diabetologia 45, 1011–1016 (2002). 38. Spiller, S. et al. Protease-triggered release of stabilized CXCL12 from coated scaffolds in an ex vivo wound model. Pharmaceutics 13, 1597 (2021). 39. Janssens, R., Struyf, S. & Proost, P. The unique structural and functional features of CXCL12. Cell Mol Immunol 15, 299 (2018). 40. Villarreal, D. et al. A Simple High Efficiency Protocol for Pancreatic Islet Isolation from Mice. J Vis Exp 2019, (2019). 41. Corbin, K. L. et al. A Practical Guide to Rodent Islet Isolation and Assessment Revisited. Biological Procedures Online 202123:123, 1–21 (2021). 42. Yolcu, E. S. et al. Induction of tolerance to cardiac allografts using donor splenocytes engineered to display on their surface an exogenous fas ligand protein. J Immunol 181, 931– 939 (2008). 43. Yolcu, E. S. et al. Pancreatic islets engineered with SA-FasL protein establish robust localized tolerance by inducing regulatory T cells in mice. J Immunol 187, 5901–5909 (2011). 44. Poznansky, M. C. et al. Active movement of T cells away from a chemokine. Nature Medicine 20006:56, 543–548 (2000). 45. Vianello, F., Olszak, I. T. & Poznansky, M. C. Fugetaxis: active movement of leukocytes away from a chemokinetic agent. J Mol Med (Berl) 83, 752–763 (2005). 46. Yolcu, E. S., Zhao, H. & Shirwan, H. Immunomodulation with SA-FasL protein as aneffective means of preventing islet allograft rejection in chemically diabetic NOD mice.Transplant Proc 45, 1889–1891 (2013). 47. Britton, C., Poznansky, M. C. & Reeves, P. Polyfunctionality of the CXCR4 / CXCL12 axis in health and disease: Implications for therapeutic interventions in cancer and immune- mediated diseases. The FASEB Journal 35, e21260 (2021). 48. Phillips, R. & Ager, A. Activation of pertussis toxin-sensitive CXCL12 (SDF-1) receptors mediates transendothelial migration of T lymphocytes across lymph node high endothelial cells. doi:10.1002 / 1521-4141(200203)32:3. 49. Sremac, M. et al. Preliminary Studies of the Impact of CXCL12 on the Foreign Body Reaction to Pancreatic Islets Microencapsulated in Alginate in Nonhuman Primates. Transplant Direct 5, (2019). 50. Sremac M, Lei J, Penson MFE, Schuetz C, Lakey JRT, Papas KK, Varde PS, Hering B, de Vos P, Brauns T, Markmann J, Poznansky MC. Preliminary Studies of the Impact of CXCL12 on the Foreign Body Reaction to Pancreatic Islets Microencapsulated in Alginate in Nonhuman Primates. Transplant Direct.2019 Apr 15;5(5):e447.Yang Y, Chen Q, Lin J, Cai Z, Liao G, Wang K, Bai L, Zhao P, Yu Z. Recent Advance in Polymer Based Microspheric Systems for Controlled Protein and Peptide Delivery. Curr Med Chem.2019;26(13):2285- 2296. 51. Liu, Z. and Habener, J.F. (2009) Stromal cell-derived factor-1 promotes survival of pancreatic beta cells by the stabilisation of beta-catenin and activation of transcription factor 7-like 2 (TCF7L2). Diabetologia 52 (8), 1589-98. 52. Alagpulinsa, D.A. et al. (2019) Alginate-microencapsulation of human stem cell- derived beta cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression. Am J Transplant.1930-1940. doi: 10.1111 / ajt.15308. 53. Chen, T. et al. (2015) Alginate encapsulant incorporating CXCL12 supports long-term allo- and xenoislet transplantation without systemic immune suppression. Am J Transplant 15 (3), 618-27 54. Sharp, C.D. et al. (2008) Stromal cell-derived factor-1 / CXCL12 stimulates chemorepulsion of NOD / LtJ T-cell adhesion to islet microvascular endothelium. Diabetes 57 (1), 102-12. 55. Papeta, N. et al. (2007) Long-term survival of transplanted allogeneic cells engineered to express a T cell chemorepellent. Transplantation 83 (2), 174-83. 56. Buchwald P., Tamayo-Garcia A, Manzoli V, Tomei AA, Stabler CL. Glucose-stimulated insulin release: Parallel perifusion studies of free and hydrogel encapsulated human pancreatic islets. Biotechnol Bioeng.2018 Jan;115(1):232-245. 57. King A, Andersson A, Strand BL, Lau J, Skjåk-Braek G, Sandler S. The role of capsule composition and biologic responses in the function of transplanted microencapsulated islets of Langerhans. Transplantation.2003 Jul 27;76(2):275-9. 58. Hu X, Gattis C, Olroyd AG, Friera AM, White K, Young C, Basco R, Lamba M, Wells F, Ankala R, Dowdle WE, Lin A, Egenberger K, Rukstalis JM, Millman JR, Connolly AJ, Deuse rigT, Schrepfer S. Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice. Sci Transl Med.2023 Apr 12;15(691):eadg5794. 59. Adrian et al., Int J Mol Sci.2021 Oct 28;22(21):11666. doi: 10.3390 / ijms222111666. 60. Righi et al. Cancer Res.2011 Jul 8;71(16):5522–5534. doi: 10.1158 / 0008-5472.CAN- 10-3143 OTHER EMBODIMENTS It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

WHAT IS CLAIMED IS:

1. A composition comprising a plurality of biotinylated microgels, wherein the plurality of biotinylated microgels comprises at least one biotinylated microgel comprising: at least one fusion protein comprising a protease-resistant C-X- C motif chemokine 12 (CXCL12) polypeptide fused to a first streptavidin moiety or first avidin moiety; and at least one fusion protein comprising a Fas ligand (FasL) polypeptide fused to a second streptavidin moiety or second avidin moiety.

2. The composition of claim 1, wherein the protease-resistant CXCL12 polypeptide comprises an amino acid sequence at least 70% identical to SEQ ID NO:

2.

3. The composition of claim 1 or 2, wherein the FasL ligand polypeptide comprises an amino acid sequence at least 70% identical to SEQ ID NO:

15.

4. The composition of any one of claims 1-3, wherein the composition comprises between 1% and 80% (w / w) of biotinylated microgels conjugated to the at least one fusion protein comprising the protease-resistant CXCL12 polypeptide fused to the first streptavidin moiety or the first avidin moiety, optionally wherein the composition comprises about 50% (w / w) of biotinylated microgels conjugated to the at least one fusion protein comprising the protease-resistant CXCL12 polypeptide fused to the first streptavidin or the first avidin moiety.

5. The composition of any one of claims 1-4, wherein the composition comprises between 1% and 80% (w / w) of biotinylated microgels conjugated to at least one fusion protein (prCXCL12) and a second immune-modulatory or immune regulatory or anti-inflammatory polypeptide fused to the second streptavidin moiety or the second avidin moiety,optionally wherein the composition comprises about 50% (w / w) of biotinylated microgels conjugated to at least one fusion protein comprising a second immune-modulatory or immune regulatory or anti-inflammatory protein to the second streptavidin moiety or the second avidin moiety.

6. The composition of any one of claims 1-5, wherein the first and / or second streptavidin or the first and / or second avidin moiety comprises an amino acid sequence at least 80% identical to SEQ ID NOs: 5-8.

7. The composition of any one of claims 1-6, wherein the biotinylated microgel comprises a diameter ranging from 150 to about 200 microns.

8. A composition comprising a plurality of biocompatible polymers, wherein the plurality of biocompatible polymer comprises at least one biocompatible polymer comprising: at least one fusion protein comprising a protease-resistant C-X-C motif chemokine 12 (CXCL12) polypeptide fused to a first streptavidin moiety or first avidin moiety; and at least one fusion protein comprising a Fas ligand (FasL) polypeptide fused to a second streptavidin moiety or second avidin moiety.

9. The composition of claim 8, wherein the composition further comprises at least one polyethylene glycol (PEG) macromer, optionally wherein the PEG macromer is selected from the group consisting of a PEG-maleimide (PEG-MAL) macromer, a PEG-acrylate (PEG- Ac) macromer, a PEG-vinylsulfone (PEG-VS) macromer, and a PEG- diacrylate (PEG-DA) macromer.

10. The composition of claim 9, wherein the PEG macromer comprises a multi- arm PEG macromer, wherein a functional group is attached to the terminal end of the arm, optionally wherein the multi-arm PEG macromer comprises at least four arms.

11. The composition of any one of claims 8-10, wherein the biotinylated microgels comprise at least one biomaterial selected from the group consisting of methacrylated hyaluronic acid (HAMA), poly(lactic-co-glycolic acid) (PLGA), alginate, gelatin, and gelatin methacrylate (GelMA).

12. The composition of any one of claims 1-7, wherein the composition further comprises at least one polyethylene glycol (PEG) macromer, optionally wherein the PEG macromer is selected from the group consisting of a PEG-maleimide (PEG-MAL) macromer, a PEG-acrylate (PEG- Ac) macromer, a PEG-vinylsulfone (PEG-VS) macromer, and a PEG- diacrylate (PEG-DA) macromer.

13. The composition of claim 12, wherein the PEG macromer comprises a multi- arm PEG macromer, wherein a functional group is attached to the terminal end of the arm, optionally wherein the multi-arm PEG macromer comprises at least four arms.

14. The composition of any one of claims 1-7, 12, or 13, wherein the composition comprises at least one biomaterial selected from the group consisting of methacrylated hyaluronic acid (HAMA), poly(lactic-co-glycolic acid) (PLGA), alginate, gelatin, and gelatin methacrylate (GelMA).

15. The composition of any one of claims 1-14, wherein the composition is configured to release at least 50% of the amount of the protease- resistant CXCL12 polypeptide and / or the FasL polypeptide over 2 to 60 days after a transplantation.

16. The composition of any one of claims 1-15, wherein the composition is biodegradable.

17. A method of treating or preventing graft rejection in a subject in need thereof, the method comprising administering an effective amount of the composition of any one of claims 1-16 to the subject in need thereof, wherein the administering occurs before transplantation of a graft, at the time of transplantation the graft, after transplantation of the graft, or any combination thereof.

18. A method of inducing an immune privileged environment in a subject in need thereof, the method comprising implanting an effective amount of the composition of any one of claims 1-16 in a subject in need thereof, wherein the implantation is localized to a site of graft transplantation.

19. A method of inducing a graft vascularization in a subject in need thereof, the method comprising implanting an effective amount of the composition of any one of claims 1-16 in a subject in need thereof, wherein the implantation is localized to a site of graft transplantation.

20. The method of any one of claims 17-19, wherein the implanting occurs before transplantation of the graft, at the time of transplanting the graft, after transplantation of the graft, or any combination thereof, optionally wherein the composition and the graft are co-implanted.

21. The method of any one of claims 17-20, wherein the subject in need thereof does not require immunosuppressive therapy after transplantation of the graft, optionally wherein the subject does not require immunosuppressive treatment for at least 60 days after transplantation of the graft.

22. The method of any one of claims 17-21, wherein the graft is an allograft.

23. The method of any one of claims 17-22, wherein the subject in need thereof is a transplant recipient or is at risk of needing a transplant, optionally whereinthe subject is a recipient of or is at risk of needing transplantation of at least one cell, at least one tissue, at least one organ, or any combination thereof.

24. The method of any one of claims 17-23, wherein the transplant is an islet cell transplant, a pancreas transplant, a skin graft, a skin transplant, a bone graft, a bone marrow graft, a bone marrow transplant, a heart transplant, a kidney transplant, a lung transplant, a liver transplant, a vascular-composite allograft, or any combination thereof.

25. A method of treating Type 1 Diabetes (T1D) in a subject in need thereof, the method comprising administering an effective amount of the composition of any one of claims 1-16 to the subject in need thereof, wherein the administering occurs before islet allotransplantation, at the time of islet allotransplantation, after islet allotransplantation, or any combination thereof.

26. The method of claim 25, wherein the effective amount of the composition and the islet allograft are co-transplanted, wherein the site of co-transplantation is an extrahepatic site, optionally wherein the site of co-transplantation is in the omentum of the subject in need thereof.

27. The method of claim 25 or 26, wherein the subject in need thereof does not require immunosuppressive treatment after islet allotransplantation, optionally wherein the subject in need thereof is normoglycemic for at least 60 days after islet allotransplantation.

28. The method of any one of claims 17-27, wherein the islet allograft survives at least 60 days after islet allotransplantation.

29. The method of any one of claims 25-28, wherein the subject in need thereof is normoglycemic after islet allotransplantation, optionally wherein the subject in need thereof does not require immunosuppressive treatment for about 1 week to 6 months after islet allotransplantation.

30. The method of any one of claims 17-29, wherein the subject in need thereof is a human.

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