Autophagy mediates osteoporotic bone regeneration induced by micro-/nano-structured modification on hydroxyapatite bioceramics

Osteoporosis (OP) is an age-related disease of bone metabolism, characterized by bone mass loss and bone microarchitecture deterioration, the poor osteogenesis microenvironment of OP caused hardly repairing of the bone defects. As a dynamic process to fuel cellular renovation, autophagy has been proved to play a vital role in regulating cell differentiation and maintaining bone homeostasis. Traditional bone repairing biomaterials are hardly repairing the bone defects under OP pathological microenvironment. Therefore, it is essential to development novel biomaterials to improve osteoporotic osteogenesis. Compared to biochemical cues, biophysical cues exhibited more advantages in biocompatible and side effects. Herein, inspired by the importance of enhanced autophagic response in osteoporotic environment, we intend to utilize the micro-/nano-structured hydroxyapatite (mnHA) bioceramics as the mimic structure of natural bone tissue to regulate autophagic activity in ovariectomy bone mesenchymal stem cells (OVX-BMSCs), finally promote to bone regeneration in OP condition. The results indicated that mnHA bioceramics promoted cell adhesion and osteogenesis of OVX-BMSCs, and enhanced autophagy level in OVX-BMSCs. In the calvarial defects of OVX-rats, the mnHA scaffold acquired excellent bone repair effect. According to the current findings, regulating the level of autophagy could be a promising strategy for improve osteoporotic osteogenesis in the future.