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Here, we developed a multifunctional composite integrating antigen\u2010extracted xenogeneic scaffold, IL\u201010\u2010loaded mesoporous polydopamine nanoparticles (MPDA@IL\u201010), and autologous bone marrow\u2010derived mesenchymal stem cells (BMSCs). The composite establishes a temporally phased immunoregulatory axis: nanoparticle\u2010delivered exogenous IL\u201010 compresses the early inflammatory window, and BMSCs then secrete endogenous anti\u2010inflammatory factors that prevent scaffold resorption and maintain a pro\u2010regenerative milieu. Beyond immunomodulation, IL\u201010 acts as a lineage\u2010determining cue, activating PI3K\u2010Akt\/Wnt signaling to drive BMSC osteogenic commitment and suppress adipogenic drift at the early differentiation stage. In a canine critical\u2010sized skull defect model, this strategy markedly enhanced radiographic and histological regeneration. By uniting temporal immune modulation with stem cell fate programming, this approach offers a translatable route to skull repair.<\/jats:p>","DOI":"10.1002\/advs.76971","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:37:56Z","timestamp":1785937076000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineered Xenogeneic Bone Scaffold with IL\u201010 Nanodelivery System: Immunomodulation and BMSC Fate Programming for Skull Defect Repair"],"prefix":"10.1002","author":[{"given":"Weihao","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Xijing Hospital Air Force Medical University (Fourth Military Medical University)  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Xijing Hospital Air Force Medical University 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