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In this study, adipose\u2010derived stem cells (ADSCs) were functionally re\u2010engineered using lipoic acid (LA) to fabricate a novel LA\u2010intervened stem cell spheroid (LA\u2010SCS) with enhanced paracrine activity and extracellular matrix (ECM) biosynthetic capacity. Subsequent decellularization mitigated immunogenicity, yielding LA\u2010intervened decellularized stem cell spheroid (LA\u2010dSCS). In vitro assays confirmed its immunomodulatory potency, as evidenced by the activation of signaling cascades associated with macrophage reprogramming, homeostasis, and autophagy. Furthermore, leveraging the intrinsic viscoelastic properties of the LA\u2010dSCS, a convenient preparation method for preparing LA\u2010dSCS derived injectable material was established, wherein LA\u2010dSCS micro\u2010particles assemble into LA\u2010dSCS granular gel. In vivo studies using diabetic rat models demonstrated closure of both wound and cranial defects. Collectively, this study established a biomimetic engineering strategy that integrates cell\u2010free bioactive aggregates with injectable granular gels, offering a novel proof\u2011of\u2011concept strategy for the regeneration of complex diabetic tissue defects.<\/jats:p>","DOI":"10.1002\/advs.202521924","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T11:04:33Z","timestamp":1775559873000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipoic Acid\u2010Intervened Decellularized Stem Cell Spheroid\u2010Based Injectable Granular Gel for Diabetic Tissue Regeneration"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1964-1130","authenticated-orcid":false,"given":"Tao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Plastic and Cosmetic Surgery Tongji Hospital School of Medicine Tongji University  Shanghai P. R. 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