Banerjee Jaideep, Das Ghatak Piya, Roy Sashwati, Khanna Savita, Sequin Emily K, Bellman Karen, Dickinson Bryan C, Suri Prerna, Subramaniam Vish V, Chang Christopher J, Sen Chandan K
Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States of America.
Department of Mechanical & Aerospace Engineering, The Ohio State University, Columbus, Ohio, United States of America.
PLoS One. 2014 Mar 3;9(3):e89239. doi: 10.1371/journal.pone.0089239. eCollection 2014.
Exogenous application of an electric field can direct cell migration and improve wound healing; however clinical application of the therapy remains elusive due to lack of a suitable device and hence, limitations in understanding the molecular mechanisms. Here we report on a novel FDA approved redox-active Ag/Zn bioelectric dressing (BED) which generates electric fields. To develop a mechanistic understanding of how the BED may potentially influence wound re-epithelialization, we direct emphasis on understanding the influence of BED on human keratinocyte cell migration. Mapping of the electrical field generated by BED led to the observation that BED increases keratinocyte migration by three mechanisms: (i) generating hydrogen peroxide, known to be a potent driver of redox signaling, (ii) phosphorylation of redox-sensitive IGF1R directly implicated in cell migration, and (iii) reduction of protein thiols and increase in integrinαv expression, both of which are known to be drivers of cell migration. BED also increased keratinocyte mitochondrial membrane potential consistent with its ability to fuel an energy demanding migration process. Electric fields generated by a Ag/Zn BED can cross-talk with keratinocytes via redox-dependent processes improving keratinocyte migration, a critical event in wound re-epithelialization.
外源施加电场可引导细胞迁移并促进伤口愈合；然而，由于缺乏合适的设备，以及在理解分子机制方面存在局限性，该疗法的临床应用仍然难以实现。在此，我们报告一种新型的、经美国食品药品监督管理局（FDA）批准的、具有氧化还原活性的银/锌生物电敷料（BED），它能够产生电场。为了深入理解BED可能如何影响伤口再上皮化的机制，我们着重研究BED对人角质形成细胞迁移的影响。对BED产生的电场进行绘图后发现，BED通过三种机制促进角质形成细胞迁移：（i）产生过氧化氢，已知其是氧化还原信号的有力驱动因素；（ii）直接参与细胞迁移的氧化还原敏感型胰岛素样生长因子1受体（IGF1R）发生磷酸化；（iii）蛋白质硫醇还原以及整合素αv表达增加，这两者均已知是细胞迁移的驱动因素。BED还增加了角质形成细胞的线粒体膜电位，这与其为需要能量的迁移过程提供能量的能力相一致。银/锌BED产生的电场可通过氧化还原依赖性过程与角质形成细胞相互作用，从而促进角质形成细胞迁移，这是伤口再上皮化中的一个关键事件。
