Promoting in vivo early angiogenesis with sub-micrometer strontium-contained bioactive microspheres through modulating macrophage phenotypes.

Early vascularization capacity of biomaterials plays an essential role in efficient wound healing and tissue regeneration, especially in large tissue tension implanting position such as bone augmentation. Strontium-contained silica-based bioactive materials have shown the role of promoting angiogenesis by stimulating osteoblasts to secrete angiogenesis related cytokines. However, osteoblasts have little effect on early angiogenesis due to the inflammatory reaction of implantation site. Here, for the first time, we found that the monodispersed strontium-contained bioactive glasses microspheres (SrBGM) could significantly promote the early angiogenesis through regulating macrophage phenotypes. After being stimulated with SrBGM in vitro, RAW cells (macrophages) presented a trend towards to M2 phenotype and expressed high level of platelet-derived growth factor-BB (PDGF-BB). Moreover, the RAW conditioned medium of SrBGM significantly enhanced the angiogenic capacity of HUVECs. The in vivo early vascularization studies showed that significant new vessels were observed at the center of SrBGM-based scaffolds after implantation for 1 week in a bone defect model of rats, suggesting their enhanced early vascularization. Due to the efficient vascularization, the in vivo new bone formation was promoted significantly. Our study may provide a novel strategy to promote the early vascularization of biomaterials through modulating the microphage phenotypes, which has wide applications in various tissue regeneration and wound healing.