Cellular Scale Curvature in Bioceramic Scaffolds Enhanced Bone Regeneration by Regulating Skeletal Stem Cells and Vascularization

Critical-sized segmental bone defects cannot heal spontaneously, leading to disability and significant increase in mortality. However, current treatments utilizing bone grafts face a variety of challenges from donor availability to poor osseointegration. Drugs such as growth factors increase cancer risk and are very costly. Here, a porous bioceramic scaffold that promotes bone regeneration via solely mechanobiological design is reported. Two types of scaffolds with high versus low pore curvatures are created using high-precision 3D printing technology to fabricate pore curvatures radius in the 100s of micrometers. While both are able to support bone formation, the high-curvature pores induce higher ectopic bone formation and increased vessel invasion. Scaffolds with high-curvature pores also promote faster regeneration of critical-sized segmental bone defects by activating mechanosensitive pathways. High-curvature pore recruits skeletal stem cells and type H vessels from both the periosteum and the marrow during the early phase of repair. High-curvature pores have increased survival of transplanted GFP-labeled skeletal stem cells (SSCs) and recruit more host SSCs. Taken together, the bioceramic scaffolds with defined micrometer-scale pore curvatures demonstrate a mechanobiological approach for orthopedic scaffold design. Critical-sized bone defects cannot heal on their own, leading to disability and death. Current treatments are costly and with significant side effects. This study introduces a porous bioceramic scaffold designed based on mechanobiological principles. High-curvature pores in the scaffold induce more bone formation, vessel invasion, and faster regeneration of bone defects by activating mechanosensitive pathways and recruiting skeletal stem cells. image