Abstract: BACKGROUND: In recent years, novel dressings, including hydrogel dressings, have become an emerging research hotspot in the field of skin wound treatment. Studies have confirmed that composite nanomedical materials loaded with copper nanoparticles can effectively promote the expression of vascular endothelial growth factor in wound tissue and promote angiogenesis, increase collagen deposition, and contribute to wound healing.
OBJECTIVE: To prepare copper phosphate nanohydrogel dressings and analyze their effects on skin wound healing in mice. 
METHODS: (1) Copper phosphate nanohydrogel dressings were prepared using agar hydrogel as the matrix, and the microstructure of the dressings was observed under a scanning electron microscope. (2) Six KM mice were randomly divided into two groups: the experimental group (n=3) received subcutaneous injection of copper phosphate nanohydrogel dressing, and the control group (n=3) received no injection. Tissue samples were collected 24 hours after injection, and hematoxylin-eosin staining was used to observe pathological changes in the heart, liver, spleen, lungs, and kidneys. (3) Escherichia coli bacterial solution was co-cultured with liquid culture medium (blank group), liquid culture medium + agar hydrogel dressing (hydrogel group), and liquid culture medium + copper phosphate nanohydrogel dressing (copper phosphate nanohydrogel group) for 8 hours. Plate coating experiments were performed to detect bacterial survival rate. (4) Fifteen KM mice were used, and a 1 cm diameter full-thickness skin defect was created on the back of each mouse. The mice were randomly divided into three groups: control group (n=5) treated with povidone-iodine and covered with gauze, hydrogel group (n=5) treated with povidone-iodine and covered with agar hydrogel dressing, and copper phosphate nanohydrogel group (n=5) treated with povidone-iodine and covered with copper phosphate nanohydrogel dressing. The dressings were changed every 3 days, and wound healing was observed. After 7 days of intervention, tissue samples were collected. Masson staining was used to observe collagen deposition (granulation tissue). CD31 immunofluorescence staining was utilized to observe angiogenesis. Western blot assay was applied to detect the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins.
RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the copper phosphate nanohydrogel dressing exhibited a porous structure with high porosity and irregular pore sizes, and a sheet-like scaffold structure was visible within the pores. (2) After subcutaneous injection of the copper phosphate nanohydrogel dressing, there were no significant pathological changes in the heart, liver, spleen, lungs, and kidneys of mice. (3) The survival rate of Escherichia coli in the copper phosphate nanohydrogel group was lower than that in the blank group and the hydrogel group (P < 0.01). (4) The wound healing rate in the copper phosphate nanohydrogel group at 5 and 7 days was higher than that in the control group and the hydrogel group (P < 0.05); the collagen deposition rate was higher than that in the control group and the hydrogel group (P < 0.01); the number of neovascularizations was higher than that in the control group and the hydrogel group; and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins was higher than that in the control group and the hydrogel group (P < 0.05). (5) The results exhibit that the copper phosphate nanohydrogel dressing can upregulate the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor and promote collagen deposition and angiogenesis, thereby accelerating skin wound healing in mice.

Key words: skin wound, copper phosphate nanoparticles, nanomedical materials, hydrogel, dressing, wound healing