Inflammatory response is a critical stage in typical wound healing. Although studies have reported that some bioactive materials can modulate the polarization of macrophages to benefit tissue regeneration, the roles of the inflammatory responses, especially the crucial roles of macrophages, in tissue regeneration stimulated by biomaterials remains unclear. Bioactive glass (BG) and hydrogel containing BG have been reported to be able to promote both hard and soft tissue regeneration. However, the critical roles of macrophages in tissue regeneration enhanced by BG have not been fully elucidated. In this study, the effects of BG/sodium alginate (SA) hydrogel (BG/SA hydrogel) on the behaviors of macrophages as well as on the interactions between macrophages and repairing cells were investigated. In addition, macrophage-depleted mice were used to investigate the necessity of macrophages in the regeneration of full-thickness skin wounds treated with BG/SA hydrogel. Our results indicated that BG/SA hydrogel could polarize macrophages towards M2 phenotype in vitro and in vivo and upregulate the expression of anti-inflammatory genes. In addition, the M2 polarized macrophages could further recruit fibroblasts and endothelial cells as well as enhance the extracellular matrix (ECM) synthesis of fibroblasts and vascularization of endothelial cells in vitro and in vivo. Depletion of macrophages in the wound sites impeded the recruitment of repairing cells and reduced the formation of blood vessels and ECM, slowing down skin regeneration. These results provide an insight into the biomaterial-immune system interactions and demonstrate that modulation of macrophages by BG/SA hydrogel in the inflammatory response is crucial in skin regeneration enhanced by the hydrogel.

炎症反应是典型伤口愈合的关键阶段。尽管已有研究报道某些生物活性物质可以调节巨噬细胞的极化，从而有利于组织再生，但在生物材料刺激的组织再生中，炎症反应的作用，尤其是巨噬细胞的关键作用仍不清楚。据报道，生物活性玻璃（BG）和含有BG的水凝胶能够促进硬组织和软组织的再生。然而，尚未完全阐明巨噬细胞在由BG增强的组织再生中的关键作用。在这项研究中，研究了BG /藻酸钠（SA）水凝胶（BG / SA水凝胶）对巨噬细胞行为以及巨噬细胞与修复细胞之间相互作用的影响。此外，消耗巨噬细胞的小鼠用于研究巨噬细胞在用BG / SA水凝胶处理的全层皮肤伤口再生中的必要性。我们的结果表明BG / SA水凝胶可以使巨噬细胞向M2表型极化在体外和体内并上调抗炎基因的表达。另外，M2极化的巨噬细胞可进一步募集成纤维细胞和内皮细胞，以及增强体外和体内成纤维细胞的细胞外基质（ECM）合成和内皮细胞的血管化。伤口部位巨噬细胞的耗竭阻碍了修复细胞的募集，并减少了血管和ECM的形成，减慢了皮肤的再生。这些结果提供了对生物材料-免疫系统相互作用的见解，并证明了BG / SA水凝胶在炎症反应中对巨噬细胞的调节对于水凝胶增强皮肤再生至关重要。