Hydrogels loaded with MSC‐derived small extracellular vesicles: A novel cell‐free tissue engineering system for diabetic wound management
Weicheng Zhong,
Hao Meng,
Liqian Ma,
Xizi Wan,
Shengqiu Chen,
Kui Ma,
Lu Lu,
Jianlong Su,
Kailu Guo,
Yufeng Jiang,
Xi Liu,
Xiaobing Fu,
Cuiping Zhang
Affiliations
Weicheng Zhong
College of Graduate Tianjin Medical University Tianjin P. R. China
Hao Meng
Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing P. R. China
Liqian Ma
Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing P. R. China
Xizi Wan
CAS Key Laboratory of Bio‐Inspired Materials and Interfacial Science Technical Institute of Physics and Chemistry Chinese Academy of Sciences Beijing P. R. China
Shengqiu Chen
Innovation Center for Wound Repair West China Hospital Sichuan University Chengdu P. R. China
Kui Ma
Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing P. R. China
Lu Lu
Institute of NBC Defence PLA Army Beijing P. R. China
Jianlong Su
Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing P. R. China
Kailu Guo
College of Graduate Tianjin Medical University Tianjin P. R. China
Yufeng Jiang
Department of Tissue Regeneration and Wound Repair PLA General Hospital Beijing P. R. China
Xi Liu
Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing P. R. China
Xiaobing Fu
Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing P. R. China
Cuiping Zhang
Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department PLA General Hospital and PLA Medical College Beijing P. R. China
Abstract With the aging and obesity era, the increasing incidence of diabetes and diabetic complications, especially the non‐healing wounds, imposes a serious economic burden on both patients and society. The complex microenvironments, including hyperglycemia, bacterial infection, ischemia, and nerve damage, lead to the prolonged inflammation and proliferation phase of diabetic wounds. Mesenchymal stem cell‐derived small extracellular vesicles (MSC‐sEVs), which contain a rich variety of therapeutic molecules, have been chased for decades because of their potential roles in cellular communication, tissue regeneration, and drug delivery. As powerful tools for the controlled‐sustained release of sEVs, biocompatible hydrogels have been applied in a wide range of biomedical applications. Herein, we first summarize the pathological features of diabetic wounds, such as angiopathy, neuropathy, and immune cell dysfunction. Then, we discuss the biological properties, therapeutic performance, and stability of pure MSC‐sEVs. After that, we discuss the components, application patterns, and responsiveness of hydrogels. Next, we discuss the loading avenues of MSC‐sEVs into hydrogel, the release behaviors of sEVs from hydrogels, and the influence of the crosslinking method on the hydrogel‐sEV composites. Finally, we provide an overview of the current applications of hydrogels loaded with MSC‐sEVs as a novel cell‐free tissue engineering system in managing diabetic wounds and propose the critical unsolved issues. This review is expected to provide meaningful guidance for developing a novel cell‐free tissue engineering system for diabetic wound management.
