{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:56:30Z","timestamp":1790283390649,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070796"],"award-info":[{"award-number":["82070796"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by \u03b2\u2010cell damage and absolute insulin deficiency. We consider combining immune intervention and \u03b2\u2010cell replacement by biological scaffold to treat T1DM. Zinc transporter 8 (ZnT8) is known to be a pancreatic islet\u2010specific autoantigen. Studies have shown that ZnT8(107\u2013115)\/HLA\u2010A2 dimers can be used as antigen\u2010specific immunosuppressants for T1DM. Mesenchymal stem cells (MSCs) can be induced to differentiate into insulin\u2010producing cells (IPCs) under certain conditions in vitro. In recent years, the development of biomaterials has provided a more suitable three\u2010dimensional microenvironment for cell transplantation. Our research group previously prepared gelatin\/polylactic acid (PLLA\/G) nanofiber scaffold by electrospinning technology, fixed GLP\u20101 analogues on the scaffold by surface modification with polydopamine (pDA) and confirmed the scaffold can promote bone mesenchymal stem cells (BMSCs) proliferation and improve cell survival rate. In addition, the scaffold can promote the differentiation of BMSCs into IPCs. Subsequently, ZnT8(107\u2013115)\/HLA\u2010A2 dimer was constructed and loaded on the scaffold and confirmed the scaffold loaded with immunosuppressants can inhibit the proliferation and cytotoxicity of specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells in vitro. This study used the above scaffold to co\u2010load ZnT8(107\u2013115)\/HLA\u2010A2 dimer and IPCs and implanted the scaffold into T1DM mice to study the blood glucose control and immunomodulatory effects on T1DM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>First, the PLLA\/G scaffold was modified with pDA and fixed with Liraglutide (LIR) to obtain the PLLA\/G\u2010pDA\u2010LIR scaffold. Rat BMSCs were loaded on the scaffold and the \u2018three\u2010step induction method\u2019 was used to induce differentiation in vitro. The insulin expression of IPCs was detected by Dithizone (DTZ) staining, glucose stimulate insulin secretion (GSIS) in vitro and intraperitoneal glucose tolerance test (IPGTT) in vivo. Then, non obese diabetes mice were modelled with T1DM and randomly divided into 5 groups. Blank control group was not treated; negative control group underwent sham surgery; positive control group was injected with IPCs through tail vein; single load scaffold group was subcutaneously transplanted with PLLA\/G\u2010pDA\u2010LIR scaffold loaded with IPCs; double load scaffold group was subcutaneously transplanted with PLLA\/G\u2010pDA\u2010LIR scaffold loaded with IPCs and ZnT8(107\u2013115)\/HLA\u2010A2 dimer. Blood glucose and body weight were measured weekly before and after transplantation. At 2, 4 and 6\u2009W after transplantation, some mice were taken from each group to detect serum insulin and C\u2010peptide, spleen lymphocyte subsets and Tregs and pancreatic Th1\/Th2 cell inflammatory factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results of insulin expression in induced differentiated IPCs show that cells with insulin expression can be obtained through the \"three\u2010step induction method\", and transplanting IPCs can effectively reduce blood glucose and improve glucose tolerance. Compared with non\u2010scaffold induced IPCs, fixing Liraglutide scaffolds can improve the insulin expression level of IPCs and promote the induction of differentiation. The results after scaffold transplantation showed that compared with the positive control group and the single load scaffold group, the blood glucose was significantly reduced, and the serum insulin and C\u2010peptide were significantly increased and lasted longer. In addition, the pathogenic T cells and inflammatory factors in the double load scaffold group were significantly reduced, and Tregs and anti\u2010inflammatory factors were significantly increased.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results show that the biological scaffold with IPCs and ZnT8(107\u2010115)\/HLA\u2010A2 dimers has the dual functions of controlling blood glucose and regulating immunity, and may effectively treat T1DM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16373","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T12:37:15Z","timestamp":1743338235000},"page":"3464-3476","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Two\u2010pronged approach: Therapeutic effect of biological scaffold combined with immune 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