2. Academic Validation
  3. Injectable Porous Microspheres Loaded With Biomimetic Preconditioned Bone Marrow Mesenchymal Stem Cell-Derived Exosomes for Vascularized Bone Regeneration

Injectable Porous Microspheres Loaded With Biomimetic Preconditioned Bone Marrow Mesenchymal Stem Cell-Derived Exosomes for Vascularized Bone Regeneration

  • Adv Sci (Weinh). 2026 Jun;13(32):e74987. doi: 10.1002/advs.74987.
Lijun Li 1,  Hao Zhang 2,  Lingtong Sun 3,  Yingfeng Su 1,  Yang Xu 4,  Jian Huang 5,  Jingchao Wen 1,  Jinjin Zhu 1,  Jianjun Ma 6,  Wenbin Xu 1
Affiliations

Affiliations

  • 1 Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine & Zhejiang Key Laboratory of Mechanism Research and Precision Repair of Orthopaedic Trauma and Aging Diseases, Hangzhou, Zhejiang, China.
  • 2 College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
  • 3 Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
  • 4 Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
  • 5 Department of Ultrasound, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 6 Department of Orthopaedic Surgery, the Fourth Affiliated Hospital of School of Medicine, International Institutes of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
PMID: 41874524 DOI: 10.1002/advs.74987
Abstract

Critical-sized bone defects remain a highly challenging clinical problem due to insufficient intrinsic self-healing capacity. Bone marrow mesenchymal stem cell (BMSC)-derived exosomes have emerged as promising cell-free therapeutic candidates for bone regeneration, owing to their paracrine effects in regulating bone regeneration-related 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-derived exosomes (BioPre-Exos) and injectable porous polydopamine (PDA)-modified 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-Exos robustly promoted BMSC migration, osteogenic differentiation, angiogenesis, and macrophage polarization toward an anti-inflammatory 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-free biomimetic synergistic delivery system holds great application potential in the clinical treatment of bone defects.

Keywords

angiogenesis; biomimetic preconditioning; bone regeneration; exosomes; injectable porous microspheres; tissue engineering.

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