{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:35:29Z","timestamp":1791333329737,"version":"4.3.1"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,7,16]],"date-time":"2022-07-16T00:00:00Z","timestamp":1657929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK128840"],"award-info":[{"award-number":["R01 DK128840"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AI132817"],"award-info":[{"award-number":["U01 AI132817"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Type 1 diabetes (T1D), an autoimmune disorder in which the insulin\u2010producing \u03b2\u2010cells in the islets of Langerhans in the pancreas are destroyed, afflicts over 1.6 million Americans. Although pancreatic islet transplantation has shown promise in treating T1D, continuous use of required immunosuppression regimens limits clinical islet transplantation as it poses significant adverse effects on graft recipients and does not achieve consistent long\u2010term graft survival with 50%\u201370% of recipients maintaining insulin independence at 5\u2009years. T cells play a key role in graft rejection, and rebalancing pathogenic T effector and protective T regulatory cells can regulate autoimmune disorders and transplant rejection. The synergy of the interleukin\u20102 (IL\u20102) and Fas immunomodulatory pathways presents an avenue for eliminating the need for systemic immune suppression by exploiting IL\u20102's role in expanding regulatory T cells and leveraging Fas ligand (FasL) activity on antigen\u2010induced cell death of effector T cells. Herein, we developed a hydrogel platform for co\u2010delivering an analog of IL\u20102, IL\u20102D, and FasL\u2010presenting microgels to achieve localized immunotolerance to pancreatic islets by targeting the upregulation of regulatory T cells and effector T cells simultaneously. Although this hydrogel provided for sustained, local delivery of active immunomodulatory proteins, indefinite allograft survival was not achieved. Immune profiling analysis revealed upregulation of target regulatory T cells but also increases in Granzyme B\u2010expressing CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells at the graft site. We attribute the failed establishment of allograft survival to these Granzyme B\u2010expressing T cells. This study underscores the delicate balance of immunomodulatory components important for allograft survival \u2013 whose outcome can be dependent on timing, duration, modality of delivery, and disease model.\n                  <\/jats:p>","DOI":"10.1002\/jbm.a.37429","type":"journal-article","created":{"date-parts":[[2022,7,16]],"date-time":"2022-07-16T08:09:33Z","timestamp":1657958973000},"page":"1728-1737","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A hydrogel platform for co\u2010delivery of immunomodulatory proteins for pancreatic islet allografts"],"prefix":"10.1002","volume":"110","author":[{"given":"Juan D.","family":"Medina","sequence":"first","affiliation":[{"name":"Biomedical Engineering Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham F.","family":"Barber","sequence":"additional","affiliation":[{"name":"Mechanical Engineering Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M.","family":"Coronel","sequence":"additional","affiliation":[{"name":"Mechanical Engineering Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Hunckler","sequence":"additional","affiliation":[{"name":"Mechanical Engineering Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.","family":"Linderman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle J.","family":"Quizon","sequence":"additional","affiliation":[{"name":"Mechanical Engineering Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahap","family":"Ulker","sequence":"additional","affiliation":[{"name":"Department of Child Health and Molecular Microbiology and Immunology, School of Medicine University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esma S.","family":"Yolcu","sequence":"additional","affiliation":[{"name":"Department of Child Health and Molecular Microbiology and Immunology, School of Medicine University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haval","family":"Shirwan","sequence":"additional","affiliation":[{"name":"Department of Child Health and Molecular Microbiology and Immunology, School of Medicine University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s J.","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Mechanical Engineering Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31506-X"},{"key":"e_1_2_8_3_1","unstructured":"Federation ID. 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