Abstract: BACKGROUND: The study of deer antler stem cells and exosomes to promote the repair of acute skin injuries has received increasing attention in recent years, but the effect and mechanism of exosomes composite hydrogel to promote the repair of burn wounds are still unclear.
OBJECTIVE: To investigate the effect of deer antler stem cell exosome composite hydrogel on the healing speed and quality of rat deep third-degree burn wound and its mechanism of action.
METHODS: Deer antler stem cell exosomes and bone marrow mesenchymal stem cell exosomes were extracted and compounded with Pluronic F-127 to prepare a temperature-sensitive hydrogel. A constant temperature and pressure burn apparatus was used to prepare a rat model of deep third-degree burn. The drug was administered to four groups: deer antler stem cell exosome composite hydrogel group, bone marrow mesenchymal stem cell exosome composite hydrogel group, human epidermal growth factor gel group, and the control group. The healing of burned rats was observed and the wound healing rate was calculated. At 28 days after burn, hematoxylin-eosin staining was used to observe the generation of skin accessory structures in the healing tissues. Masson staining was used to analyze the accumulation of collagen in the healing tissues. Immunohistochemistry was used to examine the angiogenesis and inflammatory response in the healing tissues. qRT-PCR was used to examine the expression level of mRNA of the wound healing-related genes in the healing tissues. 
RESULTS AND CONCLUSION: (1) Deer antler stem cell exosome composite hydrogel can significantly promote the healing rate of deep burn wounds in rats, and improve the quality of wound healing by promoting the regeneration of skin collateral structures, increasing the dermal thickness and enhancing the accumulation of collagen. (2) The number of myofibroblasts in the wound healing tissues of deer antler stem cell exosome composite hydrogel group was significantly reduced, and the number of neovascularization and M2 macrophages was significantly increased. (3) The mRNA levels of transforming growth factor β3 and type III collagen in the wound healing tissue of deer antler stem cell exosome composite hydrogel group were significantly higher than those of the blank group, and the mRNA levels of transforming growth factor β1, matrix metalloproteinase 3, and type I collagen were significantly lower than those of the blank group, and there was no significant difference between the bone marrow-derived mesenchymal stem cell exosome composite hydrogel group and the human epidermal growth factor gel group. In conclusion, deer antler stem cell exosome composite hydrogel can promote the healing speed and the quality of healing of deep burned wounds in rats, which may be achieved by inhibiting fibroblastogenesis, promoting angiogenesis, macrophage M2 polarization, and regulating the expression of genes for collagen production/degradation.

Key words: deer anlter stem cell-derived exosome, deep burn, myofibroblast, angiogenesis, macrophage polarization, Pluronic F-127, thermosensitive hydrogel, transforming growth factor, type III collagen, engineered exosome