A Biomimetic Scaffold for Single-Stage Reconstruction of Load-Bearing Segmental Bone Defects

Objective: This study aimed to develop a single-stage biomimetic scaffold that recapitulates hierarchical bone microenvironments for the repair of critical-sized segmental bone defects. Impact Statement: This scaffold integrates structural support and biological cues, eliminating secondary surgery and enabling load-bearing repair, thus advancing clinical translation. Introduction: The current Masquelet technique uses nondegradable spacers requiring 2 surgeries. A degradable scaffold with regenerative capacity could overcome this limitation. Methods: A porous brushite framework was combined with decellularized periosteal matrix and decellularized bone matrix to mimic periosteal, cortical, and medullary niches. In vitro bone marrow mesenchymal stem cell (BMSC) assays and an in vivo rat femoral critical-sized defect model assessed osteogenesis, angiogenesis, and biomechanics. Results: The scaffold enhanced BMSC adhesion, osteogenic, and angiogenic activities in vitro. In vivo, it promoted complete defect bridging, vascularized bone formation, direct integration, and biomechanical restoration. Histology revealed progressive scaffold replacement via accelerated endochondral ossification. Conclusion: This biomimetic scaffold effectively coordinates vascularization and bone regeneration, achieving functional single-stage repair of load-bearing segmental defects.