Bioglass promotes wound healing through modulating the paracrine effects between macrophages and repairing cells

It has been well accepted that inflammation is a critical stage in the wound healing process and the paracrine effects between macrophages and repairing cells play critical roles in wound healing. Although bioactive glass (BG), such as 45S5 bioglass, has been reported to be able to accelerate skin regeneration through enhancing angiogenesis and collagen deposition in the proliferation stage of the wound healing process, the effects of BG on the inflammation responses of wound healing have rarely been studied. To further elucidate the mechanism of BG enhancing wound healing, in this study, the effects of BG on the phenotype switch of macrophages and paracrine effects between the macrophages and repairing cells in wound healing were investigated. The results showed that BG ionic products activated macrophages towards the M2 phenotype and stimulated macrophages to express more anti-inflammatory and angiogenic growth factors compared to control medium. Conditioned medium of macrophages cultured with BG accelerated the migration of endothelial cells and fibroblasts, thus increasing the capillary-like network formation of endothelial cells and the extracellular matrix protein deposition of fibroblasts. When BG powders were applied to full-thickness excisional wounds of rats, the wound closure was accelerated by BG as compared to the control group. Reduced inflammation during initial stages of healing was observed, which was evidenced by fewer neutrophils and more M2 macrophages in the wound sites treated with BG compared to those without any treatment. All these results indicate that modulating the inflammatory response is one of the critical mechanisms for BG enhancing wound healing.