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, we report a porous bioceramic scaffold that promote bone regeneration via solely mechanobiological design. Two types of scaffolds with high versus low pore curvatures were created using high precision 3D printing technology to fabricate pore curvatures radius in the 100s of microns. While both were able to support bone formation, the high curvature pores induced higher ectopic bone formation and increased vessel invasion. Scaffolds with high curvature pores also promoted faster regeneration of critical-sized segmental bone defects by activating mechanosensitive pathways. High curvature pore recruited skeletal stem cells and type H vessels from both the periosteum and the marrow during the early phase of repair. High curvature pores had increased survival of transplanted GFP-labelled skeletal stem cells (SSCs) and recruited more host SSCs. Taken together, our bioceramic scaffolds with defined micron-scale pore curvatures demonstrate a mechanobiological approach for orthopedic scaffold design. This article is protected by copyright. All rights reserved.