Free or fixed state of nHAP differentially regulates hBMSC morphology and osteogenesis through the valve role of ITGA7

Nano-hydroxyapatite(nHAP)has been widely used in bone repair as an osteo-inductive and naturally-occurring material.However,the optimal applied form of nHAP and the underlying mechanisms involved remain unclear.Herein,to investigate into these,a range of corresponding models were designed,including three applied forms of nHAP(Free,Coating and 3D)that belong to two states(Free or fixed).The results indicate that when fixed nHAP was applied in the 3D form,optimal osteogenesis was induced in human bone marrow stem cells(hBMSCs)with increased bone volume via integrinα7(ITGA7)-mediated upregulation of the PI3K-AKT signaling pathway,while contrary results were observed with free nHAP.Ectopic osteogenesis experiments in mice subcutaneous transplantation model further confirmed the different tendencies of ITGA7 expression and osteogenesis of hBMSCs in free and fixed states of nHAP.Our results revealed that the two states of nHAP play a different regulatory role in cell morphology and osteogenesis through the valve role of ITGA7,providing cues for better application of nanoparticles and a potential new molecular target in bone tissue engineering.