{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:58:11Z","timestamp":1793642291181,"version":"4.5.1"},"posted":{"date-parts":[[2025,11,12]]},"group-title":"Bioengineering","reference-count":55,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01-DK132387"],"award-info":[{"award-number":["R01-DK132387"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01-DK124267"],"award-info":[{"award-number":["R01-DK124267"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Breakthrough T1D","award":["SRA-2019-781-S-B"],"award-info":[{"award-number":["SRA-2019-781-S-B"]}]},{"name":"Breakthrough T1D","award":["3-APF-2024-1492-A-N"],"award-info":[{"award-number":["3-APF-2024-1492-A-N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic beta cells, leaving patients dependent on exogenous insulin and at risk of severe hypoglycemic episodes. Stem cell-derived beta-like cells (sBCs) offer a promising approach for beta cell replacement therapy, but clinical translation is limited by immune-mediated rejection, recurrent autoimmunity, and inhospitable transplantation sites. Biomaterials have been investigated to provide localized immune-isolation and immunomodulation, but foreign body responses and rapid depletion of therapeutic agents remain as obstacles to clinical translation. Here, we present a microporous annealed particle (MAP) hydrogel functionalized with an anti-CD3 monoclonal antibody (\u03b1CD3) to provide a localized immunomodulatory microenvironment for beta cell replacement therapy. MAP hydrogels consisting of guest-host interlinked polyethylene glycol-maleimide (PEG-MAL) microgels supported rapid vascularization, minimal foreign body response, and engraftment of syngeneic islets in mice. \u03b1CD3 MAP hydrogel halted T cell migration\n                  <jats:italic>in vitro<\/jats:italic>\n                  and protected transplanted sBCs from immune-mediated destruction by HLA-matched diabetogenic T cells\n                  <jats:italic>in vivo<\/jats:italic>\n                  . Subcutaneous \u03b1CD3 functionalized MAP hydrogel also protected the endogenous islets in the pancreas, demonstrating potential for systemic immune modulation. These findings establish \u03b1CD3 MAP hydrogels as a promising strategy for localized immune modulation in cell replacement therapy.\n                <\/jats:p>","DOI":"10.1101\/2025.11.11.687837","type":"posted-content","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T02:30:16Z","timestamp":1763001016000},"source":"Crossref","is-referenced-by-count":2,"title":["Anti-CD3 microporous annealed particle hydrogel protects stem cell derived beta cells from autoreactive T cells"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7401-3441","authenticated-orcid":false,"given":"Adrienne E.","family":"Widener","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5371-6483","authenticated-orcid":false,"given":"Cameron T.","family":"Manson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6456-9293","authenticated-orcid":false,"given":"Jessie M.","family":"Barra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3626-1847","authenticated-orcid":false,"given":"Christopher P.","family":"Spencer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8481-2863","authenticated-orcid":false,"given":"Amanda D.","family":"Grodman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8566-1485","authenticated-orcid":false,"given":"Andrew M.","family":"Ladd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5117-2927","authenticated-orcid":false,"given":"Holger A.","family":"Russ","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8666-805X","authenticated-orcid":false,"given":"Edward A.","family":"Phelps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"9911","key":"2025111403050560000_2025.11.11.687837v1.1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0140-6736(13)60591-7","article-title":"Type 1 diabetes","volume":"383","year":"2014","journal-title":"The Lancet"},{"key":"2025111403050560000_2025.11.11.687837v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200007273430401"},{"key":"2025111403050560000_2025.11.11.687837v1.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061267"},{"key":"2025111403050560000_2025.11.11.687837v1.4","unstructured":"Association, A.D. , Stem Cell-derived Islet Therapies Shown to Reduce the Need for Injectable Insulin in Breakthrough studies demonstrate stem cell-based technologies as a potential alternative treatment for type 1 diabetes 2025: Chicago, IL"},{"issue":"5","key":"2025111403050560000_2025.11.11.687837v1.5","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/nrendo.2016.178","article-title":"Clinical pancreatic islet transplantation","volume":"13","year":"2017","journal-title":"Nature Reviews Endocrinology"},{"key":"2025111403050560000_2025.11.11.687837v1.6","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1553"},{"issue":"6","key":"2025111403050560000_2025.11.11.687837v1.7","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/s41578-019-0112-5","article-title":"Engineering immunomodulatory biomaterials for type 1 diabetes","volume":"4","year":"2019","journal-title":"Nature Reviews Materials"},{"key":"2025111403050560000_2025.11.11.687837v1.8","doi-asserted-by":"crossref","unstructured":"Brusko, T.M. , H.A. 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