School of Medicine, University of California, Irvine, California, 92617.
Beckman Laser Institute and Medical Clinic, University of California, Irvine, California, 92612.
Lasers Surg Med. 2020 Mar;52(3):196-206. doi: 10.1002/lsm.23094. Epub 2019 May 24.
Injury to healthy dermis and the dermoepidermal junction initiates a robust healing process consisting of fibrous tissue overgrowth, collagen deposition, and scar formation. The conventional management of scars and other skin injuries has largely relied upon surgical soft tissue transfer to resurface and/or replace damaged and dysmorphic tissue with new skin. However, these strategies are invasive, expensive, and may further exacerbate integumentary injury. In this study, we examine the creation of in situ redox generated pH changes in fresh human skin. We believe this process of "electrochemical therapy" (ECT) leads to changes in collagen matrix structure. Our objective is to map local tissue pH landscapes and image changes in collagen structure of non-injured skin following ECT.
Ex vivo human study involving ECT of human skin.
Remnant fresh ex vivo human facial skin from facelift operations was enveloped in saline-soaked gauze for a maximum of 2 hours prior to ECT and imaging. ECT was performed by inserting platinum-plated needle electrodes connected to a DC power supply. Voltage (4, 5, or 6 V) and time (3, 4, or 5 minutes) were varied systematically. High frequency ultrasound (25 MHz) was performed immediately after ECT on each sample. Treated samples were also imaged using multiphoton microscopy (MPM) with second harmonic generation (SHG) to specifically visualize collagen fibers in the dermis. The pH landscapes were mapped using indicator dyes in bisected specimens and the MPM images were compared with histologic findings.
Above 4 V and 3 minutes, a profound reduction in dermal collagen SHG signal was observed at the anode. Although there was less blunting of SHG signal seen at the cathode, a decrease in the fluorescence of the dermoepidermal junction was observed. The pH application suggests ECT spatial selectivity and a direct relationship between voltage and application time. Ultrasound demonstrated gas formation between the anode and cathode, which is consistent with ECT's mechanism of action. Importantly, these electrochemical changes occurred without disrupting dermal and epidermal histologic architecture.
ECT alters tissue pH leading to dermal collagen structural change. These results offer additional insight into the translational potential of ECT to locally remodel the soft-tissue matrix. Future directions aim to expand into a skin injury model to determine if similar collagen effects are observed in vivo. ECT is incredibly inexpensive (~$5) and may be a means to treat soft tissue injuries using simple needle-based devices and DC battery power supplies. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
健康真皮和表皮真皮连接处的损伤会引发一个强大的愈合过程，包括纤维组织过度生长、胶原蛋白沉积和瘢痕形成。传统的瘢痕和其他皮肤损伤的治疗方法主要依赖于手术软组织转移，用新皮肤覆盖和/或替代受损和畸形的组织。然而，这些策略具有侵入性、昂贵，并且可能进一步加剧表皮损伤。在这项研究中，我们研究了在新鲜人体皮肤中产生原位氧化还原生成 pH 变化的情况。我们相信这种“电化学治疗”（ECT）过程会导致胶原蛋白基质结构的变化。我们的目标是绘制非损伤皮肤的局部组织 pH 景观，并在 ECT 后成像胶原蛋白结构的变化。
涉及人体皮肤 ECT 的离体人体研究。
包裹在生理盐水浸湿的纱布中，从面部提升手术中取出剩余的新鲜离体人体面部皮肤，最大时间不超过 2 小时，然后进行 ECT 和成像。ECT 通过插入连接到直流电源的镀铂针电极来进行。系统地改变电压（4、5 或 6V）和时间（3、4 或 5 分钟）。在每个样品上立即进行高频超声（25MHz）。用双光子显微镜（MPM）进行处理后的样品的二次谐波产生（SHG）成像，专门观察真皮中的胶原蛋白纤维。使用分割标本中的指示剂染料绘制 pH 景观，并将 MPM 图像与组织学发现进行比较。
在 4V 以上和 3 分钟以上，在阳极处观察到真皮胶原 SHG 信号明显减少。尽管在阴极处观察到 SHG 信号的变钝程度较小，但观察到表皮真皮连接处的荧光减少。pH 值的应用表明 ECT 具有空间选择性，并且电压与应用时间之间存在直接关系。超声显示在阳极和阴极之间形成气体，这与 ECT 的作用机制一致。重要的是，这些电化学变化没有破坏真皮和表皮的组织学结构。
ECT 改变组织 pH 值，导致真皮胶原结构发生变化。这些结果为 ECT 局部重塑软组织基质的转化潜力提供了更多的见解。未来的方向旨在扩展到皮肤损伤模型，以确定是否在体内观察到类似的胶原效应。ECT 非常便宜（~5 美元），并且可能是一种使用简单的针状设备和直流电池电源治疗软组织损伤的方法。激光外科学杂志。© 2019 威利期刊公司
