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Full Length Article | Open Access

Fibrous scaffolds loaded with BMSC-derived apoptotic vesicles promote wound healing by inducing macrophage polarization

Xudong Sua,b,1, Jianye Yanga,b,1, Zhenghao Xua,b,1, Li Weia,b, Shuhao Yanga,b, Feilong Lia,b, Min Sunc, Yingkun Hua,b, Wenge Hea,b, Chen Zhaoa,b, Li Chena,b, Yonghua Yuand( ), Leilei Qina,b( ), Ning Hua,b( )
Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Laboratory of Orthopedics, Chongqing Medical University, Chongqing 400016, China
Department of Knee Joint Sports Injury, Sichuan Provincial Orthopedic Hospital, Chengdu, Sichuan 610042, China
Research Center for Pharmacodynamic Evaluation Engineering Technology of Chongqing, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China

1 These authors contributed equally to this work.

Peer review under the responsibility of the Genes & Diseases Editorial Office, in alliance with the Association of Chinese Americans in Cancer Research (ACACR, Baltimore, MD, USA).

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Abstract

Macrophages play a key role in wound healing. Dysfunction of their M0 polarization to M2 leads to disorders of the wound immune microenvironment and chronic inflammation, which affects wound healing. Regulating the polarization of M0 macrophages to M2 macrophages is an effective strategy for treating wound healing. Mesenchymal stem cells (MSCs) deliver endogenous regulatory factors via paracrine extracellular vesicles, which may play a key role in wound healing, and previous studies have shown that apoptotic bodies (ABs) are closely associated with inflammation regression and macrophage polarization. However, the specific regulatory mechanisms involved in ABs remain unknown. In the present study, we designed an MSC-AB (MSC-derived AB)-loaded polycaprolactone (PCL) scaffold, evaluated the macrophage phenotype and skin wound inflammation in vivo and in vitro, and explored the ability of MSC-AB-loaded PCL scaffolds to promote wound healing. Our data suggest that the PCL scaffold regulates the expression of the CCL-1 gene by targeting the delivery of mmu-miR-21a-5p by local sustained-release MSC-ABs, and drives M0 macrophages to program M2 macrophages to regulate inflammation and angiogenesis, thereby synergistically promoting wound healing. This study provides a promising therapeutic strategy and experimental basis for treating various diseases associated with imbalances in proinflammatory and anti-inflammatory immune responses.

Keywords

Apoptotic bodyExtracellular vesiclesMacrophage polarizationMesenchymal stem cellsmiR-21a-5pPolycaprolactoneWound healing

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Genes & Diseases
Volume 12 Issue 2,
March 2025
Article number: 101388
DOI: 10.1016/j.gendis.2024.101388
Cite this article:
Su X, Yang J, Xu Z, et al. Fibrous scaffolds loaded with BMSC-derived apoptotic vesicles promote wound healing by inducing macrophage polarization. Genes & Diseases, 2025, 12(2): 101388. https://doi.org/10.1016/j.gendis.2024.101388

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Received: 11 March 2024
Accepted: 21 June 2024
Published: 09 August 2024
© 2024 The Authors.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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