A biodegradable antimicrobial oligomer-containing hydrogel for drug-resistant bacteria-infected skin wound treatment

Abstract

Antibiotic resistance poses a serious global threat, contributing to severe clinical outcomes such as skin and soft tissue infections. Effective treatment of these infections requires both potent antimicrobial activity against resistant pathogens and wound dressings that can conform closely to the wound site. Degradable antimicrobial polymers offer a promising solution to this challenge. Unlike traditional antibiotic-loaded dressings, which often fail against multidrug-resistant (MDR) bacteria, antimicrobial polymers can effectively overcome resistance barriers. Moreover, these polymers can be easily incorporated into wound dressing materials-hydrogels being a particularly advantageous platform due to their biocompatibility and wound-conforming properties. In this study, we developed a modular strategy to integrate a biodegradable cationic antimicrobial oligomer, oligoamidine (OA1), into a thermo-responsive hydrogel. OA1 exerts a triple antibacterial mechanism involving membrane disruption, DNA binding, and ROS generation. The resulting hydrogel system can be conveniently formulated by simple mixing and undergoes a solution-gel transition at body temperature, enabling easy application to infected skin wounds. Importantly, the hydrogel matrix does not impair the bactericidal efficacy of OA1, preserving its full antimicrobial potential. This synergistic system offers an effective and user-friendly approach for treating wounds infected with MDR pathogens.

Keywords

Antimicrobial hydrogel / Wound infection / Membrane disruption / DNA targeting / Reactive oxygen species

CRediT authorship contribution statement

Min Wang: Writing - original draft, Validation, Formal analysis. Xinyun Zeng: Writing - original draft, Data curation. Xiuping Wang: Investigation. Zhiyuan Zhang: Software. Siwei Guo: Funding acquisition. Yang Deng: Funding acquisition. Xin Li: Funding acquisition. Lin Yao: Funding acquisition. Jiaqi Li: Software. Wing-Leung Wong: Writing - review & editing. Yugang Bai: Writing - review & editing. Xinxin Feng: Writing - review & editing, Resources, Project administration.

Ethics approval

All the animal studies were performed in accordance with the national and provincial regulations on animal studies. The certificate for the use of animals for research was SYXK (Hunan) 2022-0007, licensed by the Department of Science and Technology of Hunan Province on April 20, 2022, valid for 5 years. The protocols were approved by the Laboratory Animal Welfare and Ethics Review Committee, Hunan University.

Declaration of generative AI in scientific writing

Not applicable.

Funding information

The funding support from the National Key Research and Development Program of China (2023YFD1800100 to X.F. and Y. B.), National Natural Science Foundation of China (Grants 22177031 to X.F., 92163127 to Y.B.), Natural Science Foundation of Hunan Province (2024JJ4007 to X.F., 2024JJ2010 to Y.B), Science Fund for Distinguished Young Scholars of Hunan Province (2024RC3078 to X.F., 2022 RC1107 to Y.B), Hunan Provincial Key Laboratory of AntiResistance Microbial Drugs, the Third Hospital of Changsha (2023TP1013 to X.F.), Cross fusion research project of Air Force Medical University (2024JC051 to X.F.), the Health and Medical Research Fund (HMRF), Hong Kong SAR (22210412 to Wong WL), Hunan Provincial Innovation Foundation For Postgraduate (QL20220075 to J. L.) are gratefully acknowledged.

Data availability

All data supporting the findings of this study are included in this published article and its supplementary information files.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

Xinxin Feng also thanks the support from the Institute of Chemical Biology and Nanomedicine, Hunan University. The authors sincerely thank Dr. Kai Zhou (The First Affiliated Hospital of Southern University of Science and Technology), Dr. Hui Wang (Peking University People's Hospital), and Dr. Cuiyan Tan (Fifth Affiliated Hospital of Sun Yat-sen University) for providing bacterial strains. The authors thank the Analytical Instrumentation Center of Hunan University for the assistance with instrumental analysis. We acknowledge the use of Adobe Illustrator for generating figures in this study.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.pscia.2025.100091.

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