Synergistic Effect of Micro-Nano-Hybrid Surfaces and Sr Doping on the Osteogenic and Angiogenic Capacity of Hydroxyapatite Bioceramics Scaffolds.

BACKGROUND: The synergistic effect of chemical element doping and surface modification is considered a novel way to regulate cell biological responses and improve the osteoinductive ability of biomaterials. METHODS: Hydroxyapatite (HAp) bioceramics with micro-nano-hybrid (a mixture of microrods and nanorods) surfaces and different strontium (Sr) doping contents of 2.5, 5, 10, and 20% (Sr(x)-mnHAp, x: 2.5, 5, 10 and 20%) were prepared via a hydrothermal transformation method. The effect of Sr(x)-mnHAp on osteogenesis and angiogenesis of bone marrow stromal cells (BMSCs) was evaluated in vitro, and the bioceramics scaffolds were further implanted into rat calvarial defects for the observation of bone regeneration in vivo. RESULTS: HAp bioceramics with micro-nano-hybrid surfaces (mnHAp) could facilitate cell spreading, proliferation ability, ALP activity, and gene expression of osteogenic and angiogenic factors, including COL1, BSP, BMP-2, OPN, VEGF, and ANG-1. More importantly, Sr(x)-mnHAp (x: 2.5, 5, 10 and 20%) further promoted cellular osteogenic activity, and Sr(10)-mnHAp possessed the best stimulatory effect. The results of calvarial defects revealed that Sr(10)-mnHAp could promote more bone and blood vessel regeneration, with mnHAp and HAp bioceramics (dense and flat surfaces) as compared. CONCLUSION: The present study suggests that HAp bioceramics with micro-nano-hybrid surface and Sr doping had synergistic promotion effects on bone regeneration, which can be a promising material for bone defect repair.