Zn ion-incorporated injected hydrogels with reactive oxygen species and glucose scavenging capacity for diabetic wound healing

Sicong Chen; Jiajun Qiu; Shuhan Chen; Xiaoshuang Nie; Linlin Zhao; Fang Wang; Hairong Liu; Xuanyong Liu

doi:10.1093/burnst/tkae067

Zn ion-incorporated injected hydrogels with reactive oxygen species and glucose scavenging capacity for diabetic wound healing

Burns Trauma. 2025 Jan 14:13:tkae067. doi: 10.1093/burnst/tkae067. eCollection 2025.

Authors

Sicong Chen^{1

2}, Jiajun Qiu², Shuhan Chen², Xiaoshuang Nie², Linlin Zhao³, Fang Wang², Hairong Liu^{1

4}, Xuanyong Liu^{2

3}

Affiliations

¹ College of Material Science and Engineering, Hunan University, No. 2 Lushan South Road, Yuelu District, Changsha, Hunan 410082, P. R. China.
² State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, No. 1295 Dingxi Road, Changning District, Shanghai 200050, P. R. China.
³ Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, No. 2999 Renmin North Road, Songjiang District, Shanghai 201620, P. R. China.
⁴ Hunan Regenerative Elements Biotechnology Co., Ltd, Unit G2-2, Lushan Science and Technology Innovation Park, No. 966 Lushan South Road, Yuelu District, Changsha, Hunan 410012, P. R. China.

Abstract

Background: Patients with diabetic wounds often experience challenges in the repair process, owing to increased concentration of glucose and reactive oxygen species (ROS). In addition, high glucose levels usually result in bacterial infections, which in turn worsen wound healing. This study aims to develop a multifunctional hydrogel with integrated antibacterial activity, ROS scavenging, and glucose-responsive properties to accelerate healing of infected diabetic wounds.

Methods: A Zn ion-incorporated injected hydrogel was prepared using 4-carboxyphenylboronic acid-modified gelatine, tannic acid, and zinc ions. The spectra were detected using a Fourier transform infrared spectrometer and surface morphologies of hydrogels were obtained using a scanning electron microscopy. The release behavior of Zn ions was investigated using an inductively coupled plasma mass spectrometry instrument. To evaluate the antimicrobial properties of the GPT and GPT@Zn hydrogels, strains of Escherichia coli and Staphylococcus aureus were utilized. Cytocompatibility was evaluated using mouse fibroblasts (L929 cells) and human umbilical vein endothelial cells (HUVECs). Finally, diabetic wound models were constructed in rats to evaluate the effects of hydrogels on wound healing.

Results: The results show that the hydrogels are injectable and have self-healing properties. Moreover, borate ester bonds are formed in the hydrogels, which are responsive to H₂O₂ and glucose and can eliminate them. At the same time, zinc ions were released, giving the hydrogels good antibacterial efficacy, with antibacterial rates of 99.7% and 99.9% against S. aureus and E. coli, respectively. Furthermore, the hydrogels demonstrated good cell compatibility with L929 cells and HUVECs and increased the gene expression of VEGF, COL I, and COL III because of the addition of zinc ions. Based on the ROS, glucose scavenging capacity, and biological functions of zinc ions, the hydrogels advanced the recovery of S. aureus-contaminated whole skin wounds in diabetic rats.

Conclusions: This study provides a novel treatment strategy for diabetic wound healing by constructing Zn ion-incorporated injected hydrogels with reactive oxygen species and glucose-scavenging capacity.

Keywords: Antibacterial; Borate ester bond; Hydrogel; Reactive oxygen species; Zn ions.