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Yang J, Zeng W, Xu P, et al. Glucose-responsive multifunctional metal-organic drug-loaded hydrogel for diabetic wound healing. Acta Biomater. 2021;doi: 10.1016/j.actbio.2021.11.043.
Yang, J., Zeng, W., Xu, P., Fu, X., Yu, X., Chen, L., Leng, F., Yu, C., & Yang, Z. (2021). Glucose-responsive multifunctional metal-organic drug-loaded hydrogel for diabetic wound healing. Acta biomaterialia, . https://doi.org/10.1016/j.actbio.2021.11.043
Yang, Jiaxin, et al. "Glucose-responsive multifunctional metal-organic drug-loaded hydrogel for diabetic wound healing." Acta biomaterialia vol. (2021). doi: https://doi.org/10.1016/j.actbio.2021.11.043
Yang J, Zeng W, Xu P, Fu X, Yu X, Chen L, Leng F, Yu C, Yang Z. Glucose-responsive multifunctional metal-organic drug-loaded hydrogel for diabetic wound healing. Acta Biomater. 2021 Dec 05; doi: 10.1016/j.actbio.2021.11.043. Epub 2021 Dec 05. PMID: 34879294.
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Acta Biomater. 2021 Dec 05; doi: 10.1016/j.actbio.2021.11.043. Epub 2021 Dec 05.

Glucose-responsive multifunctional metal-organic drug-loaded hydrogel for diabetic wound healing.

Acta biomaterialia

Jiaxin Yang, WeiNan Zeng, Ping Xu, Xiaoxue Fu, Xiaojuan Yu, Lu Chen, Feng Leng, Chao Yu, Zhangyou Yang

Affiliations

  1. College of Pharmacy, Chongqing Engineering Research Center for Pharmacodynamics Evaluation, Chongqing Medical University, Chongqing 400016, China.
  2. Orthopedic Research institution, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610041, China.
  3. College of Pharmacy, Chongqing Engineering Research Center for Pharmacodynamics Evaluation, Chongqing Medical University, Chongqing 400016, China. Electronic address: [email protected].
  4. College of Pharmacy, Chongqing Engineering Research Center for Pharmacodynamics Evaluation, Chongqing Medical University, Chongqing 400016, China. Electronic address: [email protected].

PMID: 34879294 DOI: 10.1016/j.actbio.2021.11.043

Abstract

As the incidence of diabetes increases, its complication, diabetic foot ulcers, has become the main type of clinically chronic refractory wounds. Due to the hyperglycemic microenvironment of the diabetic wound, which leads to vascular defects and bacterial growth, the therapeutic effect of wound dressings lacking strategic design is relatively limited. In this study, we designed an injectable, "self-healing", and glucose-responsive multifunctional metal-organic drug-loaded hydrogel (DG@Gel) for diabetic wound healing. The functionalized hydrogel was prepared by phase-transfer-mediated metallo-nanodrugs, which were made by co-assembling zinc ions, organic ligands, and a small-molecule drug, deferoxamine mesylate (DFO), and the programmed loading of glucose oxidase (GOX). When injected into a diabetic wound, the GOX in DG@Gel changed the hyperglycemic wound microenvironment by decomposing excess glucose into hydrogen peroxide and glucuronic acid, which decreased the pH of the wound site. The low pH promoted the release of zinc ions and DFO, which exhibited synergistic antibacterial and angiogenesis activity for diabetic wound repair. In vitro experiments revealed the antibacterial activity and the cell proliferation, migration, and tube formation ability of DG@Gel. Moreover, in vivo experiments showed that DG@Gel can induce re-epithelialization, collagen deposition, and angiogenesis during wound healing in diabetic mice with good biocompatibility and biodegradability. The results suggest that this hydrogel is a promising innovative dressing for the treatment of diabetic wounds. STATEMENT OF SIGNIFICANCE: Diabetic ulcers, as one of the main types of chronic refractory wounds, are not treated effectively in the clinic due to a lack of strategic approach. In this study, we designed a glucose-responsive multifunctional metal-organic drug-loaded hydrogel (DG@Gel), which can change the hyperglycemic wound microenvironment by decomposing excess glucose into hydrogen peroxide and glucuronic acid. This in turn promoted the release of zinc ions and deferoxamine mesylate (DFO) in the hydrogel, which exhibited synergistic antibacterial and angiogenic activity for diabetic wound repair. Furthermore, the DG@Gel exhibited good biocompatibility and biodegradability in vivo. In general, this innovative strategy design may have great application potential in the treatment of various chronic wounds.

Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Keywords: Diabetic wound healing; Glucose-responsive; Metal–organic hydrogel; Multifunctional; Programmed loading

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this pa

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