Bioactive poly(salicylic acid)-poly(citric acid) scaffolds improve diabetic wound repair via regulating HIF-1α, Nrf2 and macrophage

Diabetic wounds environment is over-oxidized, over-inflammatory, leading to difficulties in regenerating blood vessels, and retardation of healing in diabetic wounds. Therefore, diabetic wounds can be treated from the perspective of scavenging oxidative free radicals and reducing the level of inflammation. Herein, we report a bioactive poly(salicylic acid)-poly(citric acid) (FPSa-PCG) hydrogel for diabetic wound repair. The FPSa-PCG hydrogel shows abilities of antioxidation, anti-inflammation, and regulation of macrophage phenotype. The FPSa-PCG hydrogel showed good biocompatibility, and obtain the abilities of promotion of macrophages migration, reduction of ROS generation, suppression of the M1-type macrophage polarization. FPSa and PCG could synergistically enhance the angiogenesis through upregulating the mRNA expression of HIF1Α, VEGF, and CD31 in endothelial cells and reduce the ROS level of macrophages through upregulating the mRNA expression of Nrf2. The in vivo diabetic wound model confirmed the promoting effect of FPSa-PCG hydrogel on wound closure in diabetes. The further studies found that FPSa-PCG hydrogel could induce the CD31 protein expression in the subcutaneous tissue and inhibit the TNF-a protein expression. This work shows that the simple composition FPSa-PCG hydrogel has a promising therapeutic potential in the treatment of diabetic wounds.