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Bone marrow mesenchymal stem cell (BMSC)\u2010derived exosomes have emerged as promising cell\u2010free therapeutic candidates for bone regeneration, owing to their paracrine effects in regulating bone regeneration\u2010related processes. However, enhancing exosome bioactivity via biomimetic preconditioning and developing efficient delivery vectors remain key bottlenecks in this field. Herein, we developed a synergistic bone regenerative system composed of biomimetic preconditioned BMSC\u2010derived exosomes (BioPre\u2010Exos) and injectable porous polydopamine (PDA)\u2010modified gelatin methacryloyl (GelMA) microspheres. The biomimetic preconditioning strategy adopted 3% hypoxia combined with 3D GelMA microsphere culture, mimicking the bone marrow microenvironment to regulate BMSC functions and significantly boost exosome bioactivity. Functional experiments verified that BioPre\u2010Exos robustly promoted BMSC migration, osteogenic differentiation, angiogenesis, and macrophage polarization toward an anti\u2010inflammatory phenotype in vitro. Furthermore, in a rat femoral condyle defect model, the composite system markedly improved neovascularization density and bone volume fraction, thus achieving efficient vascularized bone regeneration. These findings indicate that this cell\u2010free biomimetic synergistic delivery system holds great application potential in the clinical treatment of bone defects.<\/jats:p>","DOI":"10.1002\/advs.74987","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T19:20:16Z","timestamp":1774380016000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Injectable Porous Microspheres Loaded With Biomimetic Preconditioned Bone Marrow Mesenchymal Stem Cell\u2010Derived Exosomes for Vascularized Bone Regeneration"],"prefix":"10.1002","volume":"13","author":[{"given":"Lijun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine &amp; Zhejiang Key Laboratory of Mechanism Research and Precision Repair of Orthopaedic Trauma and Aging Diseases  Hangzhou Zhejiang 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