Molecular Mechanism Of Bioglass Promoting Wound Healingthrough Regulating Macrophages Behavior

Chronic wound healing has always been the difficulties in regenerative medicine.The treatment of chronic wound aims to transit the process from inflammation stage to repair stage.Macrophage is one of the most important and widely reported inflammatory cells.The activation of macrophages towards M1 or M2 often determines the process of wound healing.The chemokines and cytokines secreted by macrophages play important roles in the process.The chemical signal provided by bioactive glass(BG)has been proved to promote wound healing,but its molecular mechanism remains to be elucidated.In consideration of the important roles of macrophages and cell-cell interaction in wound healing,this paper focuses on the effect of BG on macrophage phenotype,behavior and the interaction between macrophages and repair cells.In this article,we first investigated the effects of BG on the phenotype and secretion capacity of macrophages.The results showed that BG was able to suppress M1 and stimulate M2 activation.The expression of pro-inflammatory factor was suppressed and the expression of growth factor was upregulated.The in vivo results showed that BG could suppress inflammation and promote the polarization towards M2 phenotype.Then,we studied the paracrine effects between macrophages,human umbilical vein endothelial cells(HUVECs)and human dermal fibroblasts(HDFs)through indirect co-culture.The results showed that BG-activated macrophages could stimulate the migration,the angiogenesis of HUVECs and the extracellular matrix deposition of HDFs.Furthermore,we studied the effects of BG-activated macrophages on the HUVEC-HDF co-cultures.The results showed that as compared to the macrophages without BG treatment,BG-activated macrophages were able to promote the paracrine effects and communications through gap junction and adhension junction between co-cultured cells.Therefore,one of the mechanisms of BG promoting wound healing is to influence the interaction between regulated macrophages and reparing cells and to affect the effects of macrophages on HUVEC-HDF interaction through modulating the behavior of macrophages.Thus,the angiogenesis and the production of extracellular matrix are promoted,and eventually wound healing is stimulated.