Hydrogels Containing Chitosan-Modified Gold Nanoparticles Show Significant Efficacy in Healing Diabetic Wounds Infected with Antibiotic-Resistant Bacteria

Abstract

Hongqi Meng,1 Ying Zhao,1 Hang Cai,2 Di You,3 Ying Wang,4 Siyu Wu,1 Yixin Wang,5 Wenlai Guo,1 Wenrui Qu1,6 1Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Pharmacy, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 3Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, 130031, People’s Republic of China; 4Institute of Neural Tissue Engineering, Mudanjiang College of Medicine, Mudanjiang, 157011, People’s Republic of China; 5Department of Plastic Surgery, First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 6Joint International Research Laboratory of Ageing Active Strategy and Bionic Health in Northeast Asia of Ministry of Education, Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Wenlai Guo, Email [email protected]: Persistent Infections and inflammation are associated with impaired wound healing in diabetic patients. There is a pressing demand for innovative antimicrobial strategies to address infections arising from antibiotic-resistant bacteria. Polymer-modified gold nanoparticles (AuNPs) show broad-spectrum antibacterial properties and significant biocompatibility. This study investigated the antibacterial and wound healing efficacy of hydrogel dressings conjugated with chitosan-AuNPs in diabetic model rats.Methods: Chitosan (CS)-functionalized gold nanoparticles (CS-AuNPs) were incorporated into hydrogel dressings (Gel/CS-AuNPs), which were formulated through the chemical cross-linking of gelatin with sodium alginate (SA). The basic characteristics of Gel/CS-AuNPs were analyzed by TEM, SEM, XRD, and UV-visible spectra. Rheological, swelling, degradation, and adhesive properties of Gel/CS-AuNPs were also determined. In vitro anti-bactericidal effects of the Gel/CS-AuNPs were analyzed with E. coli, S. aureus, and MRSA. In vitro biocompatibility of the Gel/CS-AuNPs was evaluated using NIH3T3 cells. The in vivo antibacterial and wound healing efficacy of the Gel/CS-AuNPs was analyzed in the diabetic wound model rats. Histological and immunofluorescence staining were performed to determine the status of angiogenesis, epithelization, inflammation response, and collagen deposition.Results: Gel/CS-AuNPs demonstrated significant high biodegradability, water absorption bactericidal, and biocompatibility, and slight adhesiveness. Gel/CS-AuNPs exhibited pronounced antibacterial efficacy against gram-negative, gram-positive, and MRSA in a CS-AuNPs-dose-dependent manner. In the diabetic wound model rats, Gel/CS-AuNPs effectively killed MRSA, reduced inflammation, and promoted angiogenesis and collagen deposition and remodeling at the wound site. As a result, Gel/CS-AuNPs expedited the recovery process for infected diabetic wounds. Among the hydrogels with different CS-AuNPs concentrations, Gel/CS-Au25 with 25% CS-AuNPs showed the best bactericidal and wound healing performance.Conclusion: Gel/CS-AuNPs significantly improve the healing of MRSA-infected diabetic wounds in the rat model. Therefore, Gel/CS-AuNPs show great promise for the treatment of diabetic infection wound healing. Keywords: MRSA, infection, diabetic wounds, hydrogels, CS-AuNPs, antimicrobial

Keywords

• mrsa
• infection
• diabetic wounds
• hydrogels
• cs-aunps
• antimicrobial.