Carboxymethyl chitosan (CMCS)-based hydrogels have antibacterial activity, and have shown the abilities of preventing wound infection, promoting cell proliferation, accelerating collagen deposition, and stimulating hyaluronic acid formation during wound healing. As a hormone produced by the pineal gland in humans and animals, melatonin promotes skin wound healing by regulating the release of inflammatory mediators and accelerating the proliferation and migration of cells, angiogenesis, and collagen deposition. However, the combined effects of CMCS and melatonin on wound healing remain unclear. Injectable CMCS-based hydrogels containing melatonin were prepared, and their healing effects were evaluated using a full-thickness cutaneous wound model in rats. Compared with the control and the hydrogel with no melatonin groups, the melatonin-loaded hydrogel significantly increased the percentage of wound closure, promoted the proliferation of granulation tissue and re-epithelialization, and accelerated collagen deposition. Additionally, the melatonin-loaded hydrogel promoted angiogenesis and vascular endothelial growth factor receptor protein expression and increased the expression of cyclooxygenase-2 and inducible nitric oxide synthase. The melatonin-loaded hydrogel also markedly increased the expression of collagen III, α-smooth muscle actin, and transforming growth factor-β1 proteins and reduced collagen I expression. These results suggest that the melatonin-loaded hydrogel promoted granulation tissue formation and accelerated wound healing by reducing inflammation and promoting angiogenesis and collagen deposition.

基于羧甲基壳聚糖（CMCS）的水凝胶具有抗菌活性，并且具有在伤口愈合过程中预防伤口感染，促进细胞增殖，加速胶原蛋白沉积以及刺激透明质酸形成的能力。褪黑激素是人和动物中松果体产生的一种激素，它通过调节炎症介质的释放并加速细胞的增殖和迁移，血管生成和胶原蛋白沉积来促进皮肤伤口愈合。但是，CMCS和褪黑激素对伤口愈合的综合作用仍不清楚。制备了含有褪黑激素的可注射的基于CMCS的水凝胶，并使用全厚度皮肤伤口模型在大鼠中评估了它们的愈合效果。与对照组和不含褪黑素基团的水凝胶相比，负载褪黑激素的水凝胶可显着增加伤口闭合的百分比，促进肉芽组织的增殖和上皮再形成，并加速胶原蛋白的沉积。此外，褪黑素负载水凝胶促进血管生成和血管内皮生长因子受体蛋白的表达，并增加了环氧合酶2和诱导型一氧化氮合酶的表达。负载褪黑激素的水凝胶还显着增加了胶原蛋白III，α平滑肌肌动蛋白的表达，并转化了生长因子-β1蛋白并降低了胶原蛋白I的表达。这些结果表明，负载褪黑激素的水凝胶通过减少炎症，促进血管生成和胶原蛋白沉积来促进肉芽组织形成并加速伤口愈合。