pH/glucose dual-responsive protein-based hydrogels with enhanced adhesive and antibacterial properties for diabetic wound healing

Abstract

Designing a wound dressing that offers excellent antibacterial properties while providing dual pH/glucose responsiveness for diabetic wound healing remains a considerable challenge. Herein, a 3D cross-linked native protein hydrogel was constructed through a Schiff base reaction based on -NH2 in paramyosin (PM) and -CHO in oxidized dextran (ODA) under mild conditions. Within the hydrogel, both amikacin and glucose oxidase were encapsulated during gelation. The resulting hydrogel exhibited favorable rheological properties, featuring self-healing, antibacterial activity, tissue adhesiveness, and excellent biocompatibility. Notably, the hydrogel demonstrated excellent pH/glucose dual-responsive properties. In infected wounds, the Schiff base bonds dissociated due to low pH, while in uninfected wounds with high blood glucose levels, the encapsulated glucose oxidase was functional, which also lowered the local pH level and dissociated the Schiff base bonds. Furthermore, the hydrogel quickly achieved pH/glucose dual responsiveness, leading to increased amikacin release to reduce bacterial invasion, alleviate oxidative stress, promote re-epithelialization and collagen deposition, and eventually accelerate diabetic wound healing. Collectively, the constructed hydrogel offers brand-new viewpoints on glucose-responsive biomaterials for diabetic wound therapy.

Keywords

Dual-responsive hydrogel / Schiff base / Paramyosin / Drug delivery / Diabetic wound healing

Author contributions

The authors confirm contribution to the paper as follows: study conception and design: Lv C, Zhao G, Zhang T; data collection: Yin S, Duan M, Wang Z; analysis and interpretation of results: Yin S, Zang J, Lv C, Zhang T, Fellner M; draft manuscript preparation: Yin S, Lv C, Zhang T; funding acquisition and supervision: Zhao G, Zhang T. All authors reviewed the results and approved the final version of the manuscript.

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Acknowledgments

This work was supported by National Key R & D Program of China (2021YFD2100100); the National Natural Science Foundation of China (31901638); and the 2115 Talent Development Program of China Agricultural University (109027). The authors thank Sun Mingyang and Qian Yiran for the animal experimental analysis.

Conflict of interest

The authors declare that they have no conflict of interest.

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