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

Abstract 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.