Hollow spherical mineralized scaffold integrated with a bone marrow mesenchymal stem cell-laden three-dimensional delivery system for regeneration of critical-sized bone defects

Treating critical-sized bone defects is a significant clinical challenge. Three-dimensional (3D) printing combined with bone tissue engineering (BTE) has emerged as a promising strategy for bone regeneration; however, key limitations persist, including a mismatch between scaffold degradation and osteogenesis, as well as insufficient bioactivity. In this study, we aimed to fabricate a hollow spherical mineralized biphasic calcium phosphate scaffold by 3D printing (photopolymerization via digital light processing) and incorporated within its cavity a 3D delivery system composed of methacryloyl-modified gelatin hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs). The composite scaffold was systematically evaluated using material characterization, in vitro cytocompatibility analysis, and in vivo rabbit bone defect models. Our findings demonstrated that the scaffold exhibited favorable mechanical properties, biocompatibility, and enhanced osteogenic differentiation, migration, and pro-osteogenic gene expression in BMSCs. Notably, the scaffold effectively repaired critical-sized bone defects in rabbit models within 12 weeks. This novel BTE composite scaffold provides a groundbreaking design philosophy and an innovative therapeutic strategy for complex bone defect repair.