机构:[1]School of Biomedical Engineering, Sun Yat-sen University, Shenzhen 518107, P. R. China.深圳医学信息中心中国医学科学院阜外医院深圳医院[2]The State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu 610065, P. R. China.[3]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital Sun Yat-sen University, Guangzhou 510120, P. R. China.中山大学附属第二医院
Antioxidant hydrogel has exhibited great potential for diabetic wound treatment. However, it is still a difficult challenge to realize reactive oxygen species (ROS) scavenging in an intelligent manner. Herein, we designed a novel glucose-responsive antioxidant hybrid hydrogel for enhanced diabetic wound repair. In this study, phenylboronic acid (PBA) with unique glucose-sensitivity was modified onto a hyaluronic acid (HA) chain by one-step synthesis, which was then incorporated into a polyethylene glycol diacrylates (PEG-DA) hydrogel matrix to obtain a novel hybrid hydrogel (PEG-DA/HA-PBA). Then, myricetin (MY) molecules with strong antioxidant activity were immobilized into the hybrid hydrogel by the formation of a dynamic borate bond between the polyphenol group of MY and the phenylboronic acid group of HA-PBA. The PEG-DA/HA-PBA/MY (PHM) hybrid hydrogel achieved glucose-triggered MY release, efficient ROS-scavenging (>80.0%), and also reshaped the hostile oxidative wound microenvironment (reduced MDA activity and increased SOD and GSH/GSSG levels). Furthermore, in vitro and in vivo results indicated that the PHM hydrogel platform effectively ameliorated the inflammatory response (decreased IL-6 and increased Il-10 expression), accelerated angiogenesis (increased VEGF and CD 31 expression), and increased tissue remodeling within 20 days, which was better than the nonresponsive PEG-DA/MY (PM) hydrogel platform in promoting diabetic wound healing. All results strongly suggested that this novel glucose-responsive antioxidant hybrid hydrogel platform has great potential in diabetic wound repair.
基金:
This work was supported by 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), and Key international (regional)
cooperative research projects of the National Natural Science
Foundation of China (5181001045).
第一作者机构:[1]School of Biomedical Engineering, Sun Yat-sen University, Shenzhen 518107, P. R. China.
共同第一作者:
通讯作者:
通讯机构:[1]School of Biomedical Engineering, Sun Yat-sen University, Shenzhen 518107, P. R. China.[3]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital Sun Yat-sen University, Guangzhou 510120, P. R. China.[*1]School of Biomedical Engineering, Sun Yat-sen University, Shenzhen 518107, P. R. China[*2]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital Sun Yat-sen University, Guangzhou 510120, P. R. China