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Research Article

A novel hydrogel with glucose-responsive hyperglycemia regulation and antioxidant activity for enhanced diabetic wound repair

Zejun Xu1,§, Guiting Liu3,§, Qing Li4, Jun Wu1,2( )
School of Biomedical Engineering, Sun Yat-sen University, Shenzhen 518107, China
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital Sun Yat-sen University, Guangzhou 510120, China
The State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu 610065, China
School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan 250012, China

§ Zejun Xu and Guiting Liu contributed equally to this work.

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Graphical Abstract

A novel hydrogel with glucose-responsive hyperglycemia regulation and antioxidant activity has been developed forenhanced diabetic wound repair.

Abstract

Enhanced diabetic wound repair remained a global challenge. Herein, we reported a novel hydrogel with glucose-responsive hyperglycemia regulation and antioxidant activity for enhanced diabetic wound repair. In this study, gallic acid (GA) with strong antioxidant activity was grafted onto chitosan (CS) chains by one-step synthesis, and then incorporated into poly (ethylene glycol) diacrylate (PEG-DA) hydrogel matrix to obtain a novel antioxidant hybrid hydrogel (PEG-DA/CS-GA). Meanwhile, polyethyleneimine (PEI) was modified with a unique glucose-sensitive phenylboronic acid (PBA) molecule to load insulin (PEI-PBA/insulin nano-particles, PEI-PBA/insulin NPs), which could be immobilized in the PEG-DA/CS-GA hybrid hydrogel by the formation of dynamic borate bond between the phenylboronic acid groups on the PEI-PBA and the polyphenol groups on the CS-GA. The results indicated that the PEG-DA/PEI-PBA/insulin/CS-GA (PPIC) hydrogel platform not only had remarkable biocompatibility, but also displayed extraordinary antioxidant properties (DPPH scavenging rate > 95.0%), and effectively protected cells from oxidative damage (decreased MDA levels, increased Superoxide dismutase (SOD) levels and stable GSH/GSSG levels). Meanwhile, the PPIC hydrogel also exhibited unique glucose-responsive insulin release characteristics, and effectively regulated the blood glucose level. The in vitro and in vivo results demonstrated that our PPIC hydrogel could promoted angiogenesis (increased VEGF and CD 31 expression), reshaped the inflammatory microenvironment (decreased IL-6 and increased IL-10 level), and achieved wound closure within 20 days. All these results strongly indicated that the PPIC hydrogel represented a tough and efficient platform for diabetic wound treatment.

Keywords

insulindiabetic woundglucose responsiveantioxidationhyperglycemia regulation

Electronic Supplementary Material

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Nano Research
Volume 15 Issue 6,
June 2022
Pages 5305-5315
DOI: 10.1007/s12274-022-4192-y
Cite this article:
Xu Z, Liu G, Li Q, et al. A novel hydrogel with glucose-responsive hyperglycemia regulation and antioxidant activity for enhanced diabetic wound repair. Nano Research, 2022, 15(6): 5305-5315. https://doi.org/10.1007/s12274-022-4192-y
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Received: 13 December 2021
Revised: 20 January 2022
Accepted: 25 January 2022
Published: 29 March 2022
© Tsinghua University Press 2022
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