Strontium-incorporated hydroxyapatite nanocomposites promoting bone formation and angiogenesis by modulating M2 macrophage polarization in the bone microenvironment

The treatment of osteoporosis is urgently needed in the clinic. Hydroxyapatite (HAP) has a bone-inducing ability on osteogenic differentiation. Especially, the presence of strontium component in HAP nanoparticles may improve the positive effect on bone regeneration and avoid undesirable bone resorption. However, the incorporating concentrations of strontium still need to be elucidated to balance the osteogenic function and side effects. Herein, a series of strontium-incorporated HAP nanocomposites (Srx-HAP) with different Sr incorporating molar ratio concentrations (0%, 1%, 2%, 5%, 10%, 20%, 50%, 80% and 100%) have been prepared by a simple hydrothermal route. The Srx-HAP samples exhibited uniform and well-dispersed rod-like morphology, mesoporous structure, eminent degradability and good biocompatibility. In particular, Sr20-HAP exhibited prominent advantages in osteogenic differentiation and mineralization of pre-osteoblasts cell line MC3T3-E1. Sr20-HAP nanoparticles were highly effective in enhancing the bone formation in the rat model of postmenopausal osteoporosis compared to the ovariectomy group. In addition, Sr20-HAP nanoparticles could regulate macrophage polarization to M2 type <i>in vivo</i> and <i>in vitro</i>, providing an anti-inflammatory bone microenvironment and promoting bone repair and angiogenesis. This study provides a new insight of strontium-incorporated hydroxyapatite nanoparticles as competent anti-osteoporotic biomaterials for bone formation.