Periosteum structure/function-mimicking bioactive scaffolds with piezoelectric/chem/nano signals for critical-sized bone regeneration

The critical-sized bone regeneration is still a challenge in regenerative medicine. Periosteum possesses excellent osteogenic capacity because it can provide osteogenic cells and growth factors and guide bone healing. Herein, inspired by the nanostructure/piezoelectric property of bone and the structure/function of periosteum, we report a periosteum structure/function-mimicking scaffolds with piezoelectric signal-bioactive ion-nanofibrous surface for critical-sized bone regeneration. The biomimetic scaffolds have a gradient structure including the piezoelectric polymer layer and bioactive glass nanofibrous surface. The bioactive multifunctional scaffolds could remarkably improve the proliferation, adhesion, osteogenesis differentiation of bone marrow stem cells (BMSCs), significantly enhance the formation of periosteum-like tissue and the critical-sized bone regeneration at the center of bone defect. Further studies of the molecular mechanism showed that the bioactive piezoelectric nanostructure scaffolds could activate the calcium sensing receptor of osteoblasts by accumulating Ca²⁺. Our study provides a synergistically piezoelectricity-bioactive ion-nanostructure strategy to design bioactive biomaterials for critical-sized bone regeneration.