Promoting vascularized bone regeneration via strontium-incorporated hydroxyapatite bioceramic

Abstract

Angiogenesis, well-coupled with osteogenesis, plays an indispensable and vital role in modulating hard tissue regeneration. Thus, simultaneously promoting osteogenesis and angiogenesis in bone reconstruction process is important. Essential trace elements have shown great potential in enhancing osteogenesis and angiogenesis, providing an effective strategy to design grafts for vascularized bone regeneration. In this study, four types of bioactive bioceramic, including hydroxyapatite (HA), strontium (Sr)-incorporated hydroxyapatite (Sr5-HA, Sr10-HA, Sr20-HA) with Sr ions concentrations of 0, 5, 10 and 20%, were investigated for their osteogenic and angiogenic properties. The in vitro results showed that Sr-HA could enhance the proliferation and osteogenic differentiation of BMSCs via Erk1/2 MAPK and PI3K/AKT signaling pathways, and promote the proliferation and angiogenic gene expression of HUVECs via PI3K/AKT pathways. Moreover, HUVECs conditioned medium could apparently promote the osteogenesis of BMSCs, and BMSCs conditioned medium could enhance the angiogenic capacity of HUVECs. Furthermore, in vivo angiogenesis evaluation and bone formation estimation indicated that enhanced newly-formed vessels and new bone formation were observed in Sr-HA porous scaffolds compared to pure HA scaffold. Thus, this study suggests that Sr-incorporation is a promising modification strategy for bone implants to achieve enhanced angiogenic and osteogenic capacities.