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

Abstract

Purpose

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.

Graphical Abstract

Keywords:

• MRSA
• infection
• diabetic wounds
• hydrogels
• CS-AuNPs
• antimicrobial

Ethics Approval and Consent

The use of experimental animals in this study has been approved by the Institutional Animal Care and Use Committee of Jilin University. All procedures strictly adhere to the guidelines for the care and utilization of experimental animals set forth by Jilin University.

Acknowledgments

This research received financial support from the National Natural Science Foundation of China under Grant/Award Number 81901365, the Department of Finance of Jilin Province with Grant/Award Number 2020SCZT051, and the Jilin Science and Technology Agency through Grants/Award Numbers YDZJ202201ZYTS572, YDZJ202201ZYTS071, and 20210402001GH. This work additionally received support from the Heilongjiang Natural Science Foundation of China under Grant/Award Number JQ2021H004. The authors express their gratitude to Ms. Zhengxian Xu (from Bengbu Medical University), Mr. Huidong Zhou and Dr. Rui Li (from the Second Hospital of Jilin University) for their valuable contributions to the study.

Disclosure

The authors declare no conflicts of interest in this work.