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Targeted modulation of key immunoregulatory cell populations is a promising strategy to restore tolerance to \u03b2 cells. This strategy can be used to prevent T1D onset or reverse T1D with transplanted islets. To this end, drug delivery systems can be employed to transport immunomodulatory cargo to specific cell populations that inhibit autoreactive T cell\u2013mediated destruction of the \u03b2 cell mass. The rational engineering of biomaterials into nanoscale and microscale drug carriers can facilitate targeted interactions with immune cells. The physicochemical properties of the biomaterial, the delivered immunomodulatory agent, and the target cell populations are critical variables in the design of these delivery systems. In this review, we discuss recent biomaterials-based drug delivery approaches to induce islet tolerance and the need to consider both immune and metabolic markers of disease progression.<\/jats:p>","DOI":"10.4049\/jimmunol.2300527","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T21:08:56Z","timestamp":1704229736000},"page":"216-224","source":"Crossref","is-referenced-by-count":7,"title":["Rational Engineering of Islet Tolerance via Biomaterial-Mediated Immune Modulation"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9064-7145","authenticated-orcid":false,"given":"Natalie","family":"Klug","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University , Evanston, IL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University , Evanston, IL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8945-2892","authenticated-orcid":false,"given":"Evan","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine , Chicago, IL"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"2025020405430454100_r1","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1001\/jama.2023.2063","article-title":"Effect of tight glycemic control on pancreatic beta cell function in newly diagnosed pediatric type 1 diabetes: a randomized clinical trial","volume":"329","author":"McVean","year":"2023","journal-title":"JAMA"},{"key":"2025020405430454100_r2","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"key":"2025020405430454100_r3","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.2337\/dc15-1419","article-title":"Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association","volume":"38","author":"Insel","year":"2015","journal-title":"Diabetes Care"},{"key":"2025020405430454100_r4","doi-asserted-by":"crossref","first-page":"R41","DOI":"10.1530\/JOE-21-0358","article-title":"100 years of insulin: pancreas pathology in type 1 diabetes: an evolving story","volume":"252","author":"Richardson","year":"2021","journal-title":"J. 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