期刊
NANO RESEARCH
卷 15, 期 6, 页码 5305-5315出版社
TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-022-4192-y
关键词
diabetic wound; glucose responsive; antioxidation; hyperglycemia regulation; insulin
类别
资金
- National Natural Science Foundation of China [51973243]
- Fundamental Research Funds for the Central Universities [191gzd35]
- Guangdong Innovative and Entrepreneurial Research Team Program [2016ZT06S029]
- Shenzhen Basic Research Project [JCYJ20190807155801657]
- Key international (regional) cooperative research projects of the National Natural Science Foundation of China [5181001045]
A novel hydrogel with glucose-responsive hyperglycemia regulation and antioxidant activity has been developed for enhanced diabetic wound repair. The hydrogel platform shows remarkable biocompatibility and antioxidant properties, as well as the ability to regulate blood glucose levels, promote angiogenesis, and effectively treat inflammation.
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.
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