关键词: 创面愈合, 槲皮素, 敷料, 水凝胶, 糖尿病创面, 羧甲基壳聚糖, 皮肤创面, 成纤维细胞

Abstract: BACKGROUND: Quercetin has anti-inflammatory, anti-cancer, anti-oxidation, anti-aging, anti-depression and other pharmacological effects, and has high medicinal value. Quercetin can promote wound healing in normal rats, but few drugs with quercetin as the main component have been developed, which limits its wide application in clinical practice.
OBJECTIVE: To investigate the application effect of quercetin-carboxymethyl chitosan hydrogel on diabetic wound in rats by loading quercetin with hydrogel material.
METHODS: (1) Carboxymethyl chitosan hydrogels and quercetin-carboxymethyl chitosan hydrogels were prepared respectively, and the micromorphology and in vitro drug release properties of the hydrogels were characterized. (2) Cell experiment: Mouse L929 fibroblasts were cultured in four groups. The blank control group was cultured conventionally. Carboxymethyl chitosan hydrogel, quercetin solution and quercetin-carboxymethyl chitosan hydrogel were added to pure hydrogel group, drug group, and drug-loaded hydrogel group, respectively, to detect cell proliferation and migration ability. (3) Animal experiments: Diabetic models were established in 80 SD rats. After successful modeling, full-layer skin defect wounds with a diameter of 2 cm were made on the back of rats, and these models were randomly divided into four groups. Normal saline, carboxymethyl chitosan hydrogel, quercetin solution, and quercetin-carboxymethyl chitosan hydrogel were injected into the wounds of blank control group, pure hydrogel group, drug group, and drug-loaded hydrogel group, respectively. Each group contained 20 animals, which were bound with sterile gauze. Wound healing, pathological morphology, expression of inflammatory factors, and angiogenesis were observed after operation.
RESULTS AND CONCLUSION: (1) Under scanning electron microscope, the microstructures of the two hydrogels were similar, both showed loose porous network structure, and quercetin-carboxymethyl chitosan hydrogels had good drug release performance in vitro. (2) Compared with blank control group, the cell proliferation and mobility of the other three groups were increased (P < 0.05). The cell proliferation and mobility of drug-loaded hydrogel group were higher than those of pure hydrogel group and drug group (P < 0.05). (3) The wound healing rate of the drug-loaded hydrogel group was higher than that of the other three groups at 5 and 11 days after operation. The wound healing rate of rats in the hydrogel group, pure hydrogel group, and drug group reached 100% 18 days after operation, which was higher than that in the blank control group (P < 0.05). Hematoxylin-eosin staining showed that intact skin and skin appendages were visible on the wounds of rats in the drug-loaded hydrogel group 18 days after surgery, while intact skin and skin appendages were visible on the wounds of rats in the blank control group, pure hydrogel group, and drug group 25 days after surgery. The levels of tumor necrosis factor α and interleukin-6 in the drug-loaded hydrogel group were lower than those in the blank control group at 5, 11, and 18 days after surgery (P < 0.05), and the levels of transforming growth factor β1 at 11 and 18 days after surgery were lower than those in the blank control group (P < 0.05). The mRNA expressions of CD31 and vascular endothelial growth factor α in the drug-loaded hydrogel group were higher than those in the other three groups at 11 and 18 days after operation (P < 0.05). (4) These findings indicate that quercetin in quercetin carboxymethyl chitosan hydrogel can regulate inflammatory response, accelerate angiogenesis, promote the proliferation and migration of fibroblasts, and enhance the healing of diabetic wounds in rats.

Key words: wound healing, quercetin, dressing, hydrogel, diabetic wound, carboxymethy, chitosan, skin wound, fibroblast