Mechanical stretching enhances the cellular and paracrine effects of bone marrow mesenchymal stem cells on diabetic wound healing

作者：Wei Dai, Haowei Zhou, Jincheng Du, Ruozu Xiao, Junwei Su, Zhe Liu, Rong Huang, Yuqian Li, Jing Li · 发表于：Burns & Trauma · 年份：2025 · DOI：10.1093/burnst/tkaf022 · 被引用次数：5 · 研究领域：Wound Healing and Treatments、Tissue Engineering and Regenerative Medicine、Mesenchymal stem cell research

Abstract Background Diabetic wounds present persistent clinical challenges characterized by disrupted extracellular matrix (ECM) homeostasis, which critically impedes tissue regeneration. While bone marrow-derived mesenchymal stem cells (BMSCs) exhibit therapeutic potential through ECM remodeling, conventional transplantation strategies are limited by suboptimal cell retention and transient therapeutic effects. Methods BMSCs cultured on Flexcell plates were subjected to programmable mechanical stretching using a custom-built spherical cell-stretching system. Strain rate- and duration-dependent effects on paracrine signaling and ECM secretion were longitudinally assessed through western blot ting and ELISA. The optimized mechanical parameters (15% deformation, 1440 cycles, 5-s vertex residence time) were subsequently applied to generate BMSC sheets. Comparative analyses of biological activity and mechanical properties were performed between non-stretched controls and mechanically optimized groups. In vivo therapeutic efficacy was evaluated in diabetic rat models through wound closure kinetics, Masson's trichrome staining, and immunofluorescence detection of neovascularization markers. Mechanistic insights were obtained via transcriptomic profiling of stretch-activated signaling pathways. Results Mechanical stretching significantly upregulated type I collagen, type III collagen, vascular endothelial growth factor, and transforming growth factor-beta (TGF-β) secretion in BMSCs. ...