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Research Article | Open Access

Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion

Jing Du1,2,† , Wei Liu1,†, Yajuan Song1, Yu Zhang1, Chen Dong1 , Shaoheng Xiong1, Zhaosong Huang1 , Tong Wang1, Jianke Ding1, Qiang He1 , Zhou Yu1( ), Xianjie Ma1 ( )
Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, No. 127 Changle West Road, Xi’an, Shaanxi 710032, China
Key Laboratory of Aerospace Medicine of Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, No. 169 Changle West Road, Xi’an, Shaanxi 710032, China

†These authors contributed equally to this work.

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Highlights

• This study is the first to reveal that mechanical stretch-induced skin regeneration during tissue expansion is accompanied by autophagy induction. We also monitored autophagic flux in the expanded skin at different time points after tissue expansion.

• Activating autophagy accelerated skin regeneration during tissue expansion by enhancing the proliferation and number of epidermal basal and hair follicle stem cells, reducing apoptosis, improving angiogenesis, and promoting collagen synthesis and growth factor secretion.

• Inhibition of autophagy impaired skin regeneration during tissue expansion and even increased the risk of necrosis in the expanded skin.

• Autophagy modulation may be a promising therapeutic strategy for improving the efficiency of tissue expansion and preventing the incidence of the complication of skin necrosis in clinical applications.

Abstract

Background

Tissue expansion, a technique in which skin regeneration is induced by mechanical stretch stimuli, is commonly used for tissue repair and reconstruction. In this study, we aimed to monitor the autophagy levels of expanded skin after the application of expansion stimuli and explore the effect of autophagy modulation on skin regeneration.

Methods

A rat scalp expansion model was established to provide a stable expanded skin response to mechanical stretch. Autophagy levels at different time points (6, 12, 24, 48 and 72 h after the last expansion) were detected via western blotting. The effect of autophagy regulation on skin regeneration during tissue expansion was evaluated via skin expansion efficiency assessment, western blotting, immunofluorescence staining, TUNEL staining and laser Doppler blood flow imaging.

Results

The autophagic flux reached its highest level 48 h after tissue expansion. Activating autophagy by rapamycin increased the area of expanded skin as well as the thicknesses of epidermis and dermis. Furthermore, activating autophagy accelerated skin regeneration during tissue expansion by enhancing the proliferation of cells and the number of epidermal basal and hair follicle stem cells, reducing apoptosis, improving angiogenesis, and promoting collagen synthesis and growth factor secretion. Conversely, the regenerative effects were reversed when autophagy was blocked.

Conclusions

Autophagy modulation may be a promising therapeutic strategy for improving the efficiency of tissue expansion and preventing the incidence of the complication of skin necrosis.

Keywords

AutophagyMechanical stretchSkin regenerationTissue expansion

References

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Burns & Trauma
Volume 12,
December 2024
Article number: tkad057
DOI: 10.1093/burnst/tkad057

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Cite this article:
Du J, Liu W, Song Y, et al. Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion. Burns & Trauma, 2024, 12: tkad057. https://doi.org/10.1093/burnst/tkad057

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Received: 05 April 2023
Revised: 28 August 2023
Accepted: 15 November 2023
Published: 10 October 2026
© The Author(s) 2024. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.