Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Feb 26, 2025; 17(2): 102091
Published online Feb 26, 2025. doi: 10.4252/wjsc.v17.i2.102091
Effect of adipose-derived stem cells exosomes cross-linked chitosan-αβ-glycerophosphate thermosensitive hydrogel on deep burn wounds
Lei Xu, Dan Liu, Hai-Long Yun, Wei Zhang, Li Ren, Wen-Wen Li, Chuan Han
Lei Xu, Hai-Long Yun, Department of Pathology, General Hospital of the Western Theater Command, Chengdu 610038, Sichuan Province, China
Dan Liu, Wei Zhang, Li Ren, Wen-Wen Li, Chuan Han, Department of Endocrinology, General Hospital of the Western Theater Command, Chengdu 610038, Sichuan Province, China
Co-first authors: Lei Xu and Dan Liu.
Author contributions: Xu L and Liu D contributed equally to this study and as co-first authors. Xu L, Liu D, Zhang W, Ren L, Li WW, and Han C contributed to manuscript writing; Xu L and Yun HL were responsible for the preparation of figures; and all authors participated in the manuscript review.
Supported by the Incubation Program of the General Hospital of the Western Theater Command, No. 2021-XZYG-C29 and No. 2021-XZYG-B32.
Institutional animal care and use committee statement: The animal care and experimental protocols were approved by the Institutional Animal Care and Use Committee of the General Hospital of the Western Theater Command (Approval Number: XBZQZYY2021-046). The study was designed to minimize animal distress, and all rats were humanely euthanized using an overdose of barbiturate through intravenous injection of 150 mg/kg pentobarbital sodium for tissue collection, aligning with the committee’s guidelines for ethical animal research. The committee ensures that all research involving animals adheres to the principles of the 3Rs (replacement, reduction, refinement) to minimize pain or discomfort. All efforts were made to ensure the welfare of the animals throughout the study, and the methods used for euthanasia were in strict accordance with the guidelines for humane endpoints.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chuan Han, MD, Associate Chief Physician, Department of Endocrinology, General Hospital of the Western Theater Command, No. 270 Tianhui Road, Chengdu 610038, Sichuan Province, China. hanchuan3012005173@126.com
Received: October 8, 2024
Revised: December 16, 2024
Accepted: February 7, 2025
Published online: February 26, 2025
Processing time: 138 Days and 16.8 Hours
Abstract
BACKGROUND

Burn wound management is challenging, and while mesenchymal stem cell-derived exosomes show therapeutic potential, optimal delivery methods are unclear.

AIM

To study chitosan (CS)-αβ-glycerophosphate (CS-αβ-GP) hydrogel crosslinked with adipose-derived stem cell exosomes (ASC-Exos) for healing deep burn injuries.

METHODS

Rats with deep burn injuries were divided into the CS + ASCs-Exos group, the ASCs-Exos group, the CS group, and the control group. The healing rates on days 4, 7, and 14 after treatment were analyzed using ImageJ software. On day 14, the tissues were stained with hematoxylin and eosin staining, Masson’s trichrome staining, and immunohistochemical analysis to evaluate tumor necrosis factor α, interleukin-6 (IL-6), IL-1α, IL-10, transforming growth factor β, and epidermal growth factor. The mRNA levels of IL-1α, CD86, C-C motif chemokine ligand 22, and CD163 were evaluated through quantitative polymerase chain reaction.

RESULTS

The CS + ASC-Exos group exhibited enhanced healing, reduced lymphocyte infiltration, blood vessels, and muscle fiber distribution. Increased IL-10, transforming growth factor β, and epidermal growth factor and decreased tumor necrosis factor α, IL-1α, and IL-6 expression were observed. Quantitative polymerase chain reaction revealed reduced IL-1α and CD86 and increased C-C motif chemokine ligand 22 and CD163 expression. Protein analysis showed downregulation of phosphorylated inhibitor of kappa Balpha and P65 in the nuclear factor κB (NF-κB) pathway. ASC-Exos crosslinked with CS-αβ-GP hydrogel demonstrates superior effects in anti-inflammation, wound healing promotion, and promotion of M1 macrophage transformation to M2 macrophage by blocking the NF-κB pathway compared to ASC-Exos alone.

CONCLUSION

Our research demonstrates that the ASC-Exos cross-linked CS-αβ-GP hydrogel represents an advanced therapeutic approach for treating deep burn wounds. It has anti-inflammatory effects, promotes wound healing, and facilitates the transition of M1 macrophages to M2 macrophages by blocking the NF-κB pathway.

Keywords: Adipose-derived stem cells; Exosomes; Hydrogel; Burn; Wound healing

Core Tip: Studies indicate that the exosome hydrogel composite demonstrates exceptional efficacy in facilitating the healing of deep burn wounds and managing infection. It has anti-inflammatory effects, promotes wound healing, and facilitates the transition of M1 macrophages to M2 macrophages by blocking the nuclear factor κB pathway, thereby offering a novel strategy for the clinical utilization of mesenchymal stem cell-derived exosomes.