Abstract: BACKGROUND: Excessive reactive oxygen species and bacterial infections in diabetic wounds can interfere with cell activity and function, increasing the difficulty of wound healing. Additionally, the lack of bioactive substances is an important factor contributing to delayed wound healing.
OBJECTIVE: To investigate the protective effects of metal organic framework/carboxymethyl chitosan-oxidized sodium alginate/platelet-rich plasma hydrogel on cells under oxidative stress and in vitro antibacterial activity, as well as its role in the repair of diabetic infected wounds.
METHODS: Manganese oxide and silver nanoparticles were loaded onto UIO-66-NH2 to prepare metal organic frameworks, and then metal organic framework/carboxymethyl chitosan-oxidized sodium alginate/platelet-rich plasma hydrogels were prepared. The structure and morphology of the hydrogels and their effects on the proliferation and morphology of NIH-3T3 fibroblasts were characterized. Under H2O2-induced oxidative stress, the effects of the hydrogels on the proliferation, activity, reactive oxygen species levels, cell cycle and cell migration of NIH-3T3 fibroblasts were characterized. The inhibitory effects of the hydrogels on Staphylococcus aureus and Escherichia coli in vitro were characterized. Twelve SD rats were selected and the diabetic model was established by intraperitoneal injection of streptozotocin. After the model was successfully established, a circular (20 mm in diameter) full-thickness skin wound was made on the back of the rats and Staphylococcus aureus suspension was dripped. After 12 hours, the rats were randomly divided into two intervention groups: the control group (n=6) had the wound wrapped with gauze, and the experimental group had the wound covered with metal organic framework/carboxymethyl chitosan-oxidized sodium alginate/platelet-rich plasma hydrogel and wrapped with gauze. The wound healing was observed regularly. On day 14 of treatment, the wound was collected and the wound healing quality was observed by hematoxylin-eosin staining and Masson staining.
RESULTS AND CONCLUSION: (1) The components in the metal organic framework/carboxymethyl chitosan-oxidized sodium alginate/platelet-rich plasma hydrogel were cross-linked to present a uniform network structure, which could promote the proliferation of NIH-3T3 fibroblasts without affecting the cell morphology. Under oxidative stress, the hydrogel could reduce the level of reactive oxygen species and the number of dead cells in NIH-3T3 fibroblasts, reverse cell cycle arrest, and increase cell proliferation rate and migration ability. The hydrogel could significantly inhibit the growth of Staphylococcus aureus and Escherichia coli. (2) The diabetic rat infection wound repair experiment showed that the metal organic framework/carboxymethyl chitosan-oxidized sodium alginate/platelet-rich plasma hydrogel could promote wound repair and improve the quality of wound healing. (3) The results show that the metal organic framework/carboxymethyl chitosan-oxidized sodium alginate/platelet-rich plasma hydrogel can protect cells from the influence of excessive reactive oxygen species, improve the activity and functional expression of cells in an oxidative stress environment, and significantly promote the healing of infected wounds in diabetic rats. 

Key words: platelet-rich plasma, metal organic framework, carboxymethyl chitosan, oxidized sodium alginate, hydrogel, fibroblast, antibacterial, antioxidant, engineered skin materia