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Research Article

Piezoelectric film promotes skin wound healing with enhanced collagen deposition and vessels regeneration via upregulation of PI3K/AKT

Qi Xu1,,§Wufei Dai1,§Peizhe Li2,§Qinglin Li2Zhen Gao1Xiaoli Wu1Wei Liu1( )Wenbo Wang1( )
Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Research Institute of Plastic Surgery, Shandong Second Medical University, Weifang 261000, China
Present address: Department of Surgery, Air Force Medical Center, PLA, Beijing 100142, China

§ Qi Xu, Wufei Dai, and Peizhe Li contributed equally to this work.

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Graphical Abstract

A self-powered repetitive mechanical impact electrical stimulation (RMI-ES) system, based on BaTiO3/polydimethylsiloxane (PDMS) piezoelectric composite films, was used to promote skin wound healing. It enhanced fibroblast proliferation, reduced inflammation, and promoted collagen deposition and new blood vessel formation through the PI3K/AKT pathway.

Abstract

Skin wounds are common in accidental injuries, and the intricacies of wound repair are closely linked to endogenous electric fields. Electrical stimulation plays a pivotal role in the restorative processes of skin injuries, encompassing collagen deposition, angiogenesis, inflammation, and re-epithelialization. Employing electrical stimulation therapy replicates and enhances the effects of endogenous wound electric fields by applying an external electric field to the wound site, thereby promoting skin wound healing. In this study, we developed a self-powered repetitive mechanical impacts-electrical stimulation (RMI-ES) system utilizing a BaTiO3/polydimethylsiloxane (PDMS) piezoelectric composite film. Compared to conventional electrical stimulation devices, the fabricated piezoelectric composite film efficiently harvests energy from the pressure applied by the stimulation device and the tensile force occurring during natural rat activities. The results demonstrated that piezoelectric stimulation generated by the composite membrane expedited the cell cycle, promoting fibroblast proliferation. Additionally, piezoelectric stimulation induced favorable changes in fibroblast gene expression, including increased expression of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), collagen 1, collagen 3, vascular endothelial growth factor (VEGF), and alpha-smooth muscle actin (α-SMA), while reducing interleukin-6 (IL-6) expression. Transcriptome analysis revealed that piezoelectric stimulation may induce fibroblast migration, proliferation, and collagen expression by influencing PI3K/AKT serine/threonine kinase (AKT) pathways. Further confirmation through the addition of the PI3K inhibitor LY294002 validated that piezoelectric stimulation can regulate the repair process after skin injury through the pathway. Importantly, in vivo results demonstrated that the electric field at the wound site effectively promoted wound healing, reduced inflammation, and stimulated collagen deposition and neovascularization. This study emphasizes the role of the piezoelectric membrane as an effective, safe, and battery-free electrical stimulator crucial for skin wound healing.

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Nano Research
Pages 7461-7478
Cite this article:
Xu Q, Dai W, Li P, et al. Piezoelectric film promotes skin wound healing with enhanced collagen deposition and vessels regeneration via upregulation of PI3K/AKT. Nano Research, 2024, 17(8): 7461-7478. https://doi.org/10.1007/s12274-024-6717-z
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Received: 01 March 2024
Revised: 18 April 2024
Accepted: 22 April 2024
Published: 25 June 2024
© Tsinghua University Press 2024
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