Engineered hierarchical 3D scaffold promotes bone regeneration through enhanced mechanotransduction.

Human bone has an innate capacity for self-repair, but it is insufficient to heal critical-sized bone defects. While current scaffolds have the potential to promote the repair of critical-sized defects, this capacity is hindered by their inadequate bioactivity and osteoconductivity. Therefore, a nano-/micro-hierarchical scaffold with a tunable surface architecture was developed to enhance bone regeneration. The resulting biointerface markedly promoted osteogenic differentiation of bone marrow mesenchymal stem cells in a non-linear, roughness-dependent manner. Furthermore, in vivo results displayed that scaffolds with a fiber roughness of approximately 400 nm exhibited the highest potency on bone defect repair. The promising performance of the hierarchical scaffold was found to result from enhanced cellular mechanotransduction by its nano-/micro-hierarchical architectures at the scaffold's biointerface. The present study offers an interesting strategy to address the challenge of critical-sized bone defect repair based on mechanobiology.