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

Adv Healthc Mater. 2024 Nov;13(29):e2401667. doi: 10.1002/adhm.202401667. Epub 2024 Jul 7.

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.

Keywords: 3D printing; bioceramic; bone scaffold; mechanobiology; skeletal stem cell.

MeSH terms

  • Animals
  • Bone Regeneration* / drug effects
  • Bone Regeneration* / physiology
  • Ceramics* / chemistry
  • Ceramics* / pharmacology
  • Mice
  • Neovascularization, Physiologic / drug effects
  • Osteogenesis / drug effects
  • Osteogenesis / physiology
  • Porosity
  • Printing, Three-Dimensional
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Tissue Engineering / methods
  • Tissue Scaffolds* / chemistry