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World J Diabetes. Nov 15, 2022; 13(11): 949-961
Published online Nov 15, 2022. doi: 10.4239/wjd.v13.i11.949
Combination therapy of hydrogel and stem cells for diabetic wound healing
Jia-Na Huang, Hao Cao, Kai-Ying Liang, Li-Ping Cui, Yan Li
Jia-Na Huang, Hao Cao, Kai-Ying Liang, Yan Li, School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, Guangdong Province, China
Jia-Na Huang, Hao Cao, Kai-Ying Liang, Yan Li, Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, China
Li-Ping Cui, Endocrinology Department, Panyu Central Hospital, Guangzhou 511400, Guangdong Province, China
Author contributions: Li Y designed the research study; Huang JN and Cao H searched the literature and drafted the initial manuscript; Liang KY and Cui LP provided further revision; all authors have read and approved the final version of the manuscript.
Supported by the Shenzhen Basic Research Project, No. JCYJ20190807155805818; and the Foundation of Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument, No. 2020B1212060077.
Conflict-of-interest statement: There are no conflicts of interest to report.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Yan Li, PhD, Associate Professor, School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, No. 66 Gongchang Road, Shenzhen 518107, Guangdong Province, China.
Received: August 28, 2022
Peer-review started: August 28, 2022
First decision: September 12, 2022
Revised: September 25, 2022
Accepted: November 2, 2022
Article in press: November 2, 2022
Published online: November 15, 2022

Diabetic wounds (DWs) are a common complication of diabetes mellitus; DWs have a low cure rate and likely recurrence, thus affecting the quality of patients’ lives. As traditional therapy cannot effectively improve DW closure, DW has become a severe clinical medical problem worldwide. Unlike routine wound healing, DW is difficult to heal because of its chronically arrested inflammatory phase. Although mesenchymal stem cells and their secreted cytokines can alleviate oxidative stress and stimulate angiogenesis in wounds, thereby promoting wound healing, the biological activity of mesenchymal stem cells is compromised by direct injection, which hinders their therapeutic effect. Hydro-gels form a three-dimensional network that mimics the extracellular matrix, which can provide shelter for stem cells in the inflammatory microenvironment with reactive oxygen species in DW, and maintains the survival and viability of stem cells. This review summarizes the mechanisms and applications of stem cells and hydrogels in treating DW; additionally, it focuses on the different applications of therapy combining hydrogel and stem cells for DW treatment.

Keywords: Combination therapy, Mesenchymal stem cells, Hydrogel, Diabetic wound, Cells delivery, Wound healing

Core Tip: Diabetic wounds are a common diabetes mellitus complication with a low cure rate and likely recurrence. Although stem cell therapy is suitable for diabetic wound healing, simple transplantation methods, such as intravenous, subcutaneous, intramuscular, and local injection, are not conducive to cell survival, thus resulting in compromised efficacy. To improve the outcome of stem cell therapy, researchers have designed different types of hydrogels for stem cell delivery to ensure cell viability and paracrine functions. Herein, we discuss the current roles and applications of hydrogel and stem cell combination therapy for diabetic wound treatment.