Green synthesis of silver nanoparticles using Fructus Aurantii-loaded Citrus pectin hydrogel for accelerated healing of MRSA-infected diabetic wounds

Abstract

To address the challenges of bacterial infection and wound healing in diabetic wounds, we developed a multi-bioactive citrus pectin hydrogel (CPH) loaded with Fructus Aurantii-derived green synthesized silver nanoparticles (FA-Ag NPs), termed FA-Ag NPs/CPH. Here, FA-Ag NPs exhibited excellent antibacterial activity alongside antioxidant, anti-inflammatory and wound-healing activities. When combined with CPH, this formulation significantly enhanced biocompatibility and accelerated wound repair processes. In vitro experiments demonstrated sustained release of FA-Ag NPs, achieving a 97.66 % eradication rate against methicillin-resistant Staphylococcus aureus (MRSA) through disrupting bacterial membrane integrity by inducing intracellular content leakage and inhibiting ATP synthesis. The hydrogel also demonstrated antioxidant and anti-inflammatory activities, promoting cell migration and angiogenesis. In vivo assays showed that FA-Ag NPs/CPH reduced wound area to 8 % by day 11 (vs. 23.4 % in control group). This therapeutic effect was attributable to suppressing MRSA infection, promoting macrophage polarization from pro-inflammatory M1 to reparative M2 phenotype, accelerating cellular migration and neovascularization, stimulating collagen deposition, and promoting skin appendage development. Collectively, these findings confirm the combined antibacterial and wound-healing efficacy of FA-Ag NPs/CPH with superior biocompatibility, highlighting its promising clinical application potential. However, further validation of long-term biological effects through large animal studies is still required.

Keywords: Citrus pectin; Fructus Aurantii-silver nanoparticles; Green synthesis; Hydrogel; MRSA-infected diabetic wound.