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Review
. 2023 Sep 22:23:100810.
doi: 10.1016/j.mtbio.2023.100810. eCollection 2023 Dec.

Extracellular vesicle biopotentiated hydrogels for diabetic wound healing: The art of living nanomaterials combined with soft scaffolds

Zhenzhen Yan  1 , Tinglin Zhang  2 , Yuxiang Wang  1 , Shichu Xiao  1 , Jie Gao  2
Affiliations
Review

Extracellular vesicle biopotentiated hydrogels for diabetic wound healing: The art of living nanomaterials combined with soft scaffolds

Zhenzhen Yan et al. Mater Today Bio. .

Abstract

Diabetic wounds (DWs) pose a major challenge for the public health system owing to their high incidence, complex pathogenesis, and long recovery time; thus, there is an urgent need to develop innovative therapies to accelerate the healing process of diabetic wounds. As natural nanovesicles, extracellular vesicles (EVs) are rich in sources with low immunogenicity and abundant nutritive molecules and exert potent therapeutic effects on diabetic wound healing. To avoid the rapid removal of EVs, a suitable delivery system is required for their controlled release. Owing to the advantages of high porosity, good biocompatibility, and adjustable physical and chemical properties of hydrogels, EV biopotentiated hydrogels can aid in achieving precise and favorable therapy against diabetic wounds. This review highlights the different design strategies, therapeutic effects, and mechanisms of EV biopotentiated hydrogels. We also discussed the future challenges and opportunities of using EV biopotentiated hydrogels for diabetic wound healing.

Keywords: Design strategy; Diabetic wounds; Extracellular vesicle; Hydrogel; Mechanism.

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Conflict of interest statement

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 paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Synthesis of hydrogels from different material sources. (A) Sodium alginate hydrogel loaded with ADSC-EXOs. Reproduced with permission from Ref. [85], Copyright © 2019 Wiley Periodicals, Inc. (B) The combination of GMSC-derived exosomes and chitosan/silk protein hydrogel. Reproduced with permission from Ref. [35], Copyright © 2017 Frontiers. (C) Preparation process of PEG hydrogel loaded with M2-Exos (Exogel). Reproduced with permission from Ref. [108], Copyright © 2020 Elsevier B.V. (D) Schematic illustration of the exo@H pro-healing mechanism. Reproduced with permission from Ref. [50], Copyright © 2022 Wiley-VCH GmbH. ADSC-EXOs, adipose-derived mesenchymal stem cell-derived exosomes; GMSC, gingiva-derived mesenchymal stem cells.
Fig. 2
Fig. 2
Anti-inflammatory mechanism of hydrogels loaded with EVs. (A) Schematic diagram of the poly (SBMA) hydrogel for wound closure. Reproduced with permission from Ref. [127], Copyright © 2018 Elsevier Ltd. (B) Schematic illustration of NV@BSA-GEL hydrogel fabrication. (C) Anti-inflammatory effects of the NV@BSA-GEL hydrogel on macrophages. Reproduced with permission from Ref. [117], Copyright © 2023 Elsevier Ltd. SBMA, sulfobetaine methacrylate.
Fig. 3
Fig. 3
Antioxidant mechanism of hydrogels loaded with EVs. (A) HA-DA/hydrogel synthesis and antioxidant application. Reproduced with permission from Ref. [135], Copyright © 2019 Elsevier B.V. (B) Schematic illustration of the preparation and application of the ADSC-exo@MMP-PEG smart hydrogel. (C) Fluorescence images of ROS in HDFs, HaCaT cells, and HUVECs. (D) Statistical analysis of C. Reproduced with permission from Ref. [66], Copyright © 2022 Elsevier Ltd.
Fig. 4
Fig. 4
Anti-infection mechanism of hydrogels loaded with EVs. (A) Antibacterial mechanism of chitosan and its derivatives. Reproduced with permission from Ref. [143], Copyright © 2020 Elsevier B.V. (B) Construction and application of the multifunctional HA@ MnO2/FGF-2/Exos hydrogel. (C) Viability of P. aeruginosa, S. aureus, and MRSA after incubation for 4 h at 37 °C. Reproduced with permission from Ref. [113], Copyright © 2021 Wiley-VCH GmbH. (D) Scheme of pH-responsive exosome release in the FHE hydrogel. (E) Antimicrobial efficiency of FHE hydrogels. Reproduced with permission from Ref. [32], Copyright © Ivyspring International Publisher.
Fig. 5
Fig. 5
Pro-angiogenesis mechanism of hydrogels loaded with EVs. (A) Schematic of the preparation of the PEG/Ag/CNT-M + E hydrogel. (B) Schematic diagram showing the mechanism of microvascular injury protection by PEG/Ag/CNT-M + E hydrogels. (C) Coimmunofluorescence of mitochondria and F-actin. Reproduced with permission from Ref. [119], Copyright © 2023 Elsevier. (D) μCT images of angiogenesis treated with CS-SMSC-126-Exos. (E) Immunofluorescence staining of CD31 and α-SMA at 7 and 14 days after the operation. Reproduced with permission from Ref. [154], Copyright © 2016 Wiley Periodicals, Inc. (F) Formation of Gel-VH-EVs for pro-angiogenesis. Reproduced with permission from Ref. [155], Copyright © 2022 Elsevier Ltd.
Fig. 6
Fig. 6
Pro-cell proliferation mechanism of hydrogels loaded with EVs. (A) Photographs of wound closure after intervention with the ADSC-exo-loaded β-ChNF hydrogel. (B) Wound closure rates of the indicated treatment groups. (C) Expression of Actn2 and Aldoa protein in rat skin. Reproduced with permission from Ref. [156], Copyright © 2022 VIA Medicine Journals. (D) Schematic diagram of the hUMSC-EM hydrogel for skin wound healing. (E) hUMSC-derived EMs promoted the proliferation of hDF-a. Reproduced with permission from Ref. [115], Copyright © 2022 Frontiers.
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