Toward smart personalized electrotherapy for enhanced healing of ischemic wounds

不愈合的缺血性伤口是有身体损伤和/或残疾的退伍军人的主要问题。 这些慢性伤口会引起严重的疼痛和残疾，在高危人群中发生的频率高得惊人。 由退伍军人医疗保健管理局（VHA）照顾的退伍军人群体。使用电 用于缺血性伤口治疗的电刺激（ES）早已为人所知，但是结果是可变的。在 在以前的工作中，我们开发了一种无束缚的电子绷带，具有表面刺激的所有组件 系统安装在柔性基板上。我们系统地研究了一系列临床应用的影响， 相关的ES，并发现两个范例，显着提高愈合的大鼠缺血性伤口模型。一 还发现这些范例中的一种在急性临床前模型中显著减少伤口感染， 临床相关的大伤口。 该项目将在Smart的相关大型动物模型中提供转化开发和测试 模块化自适应电疗输送系统（SmartMAEDS）提供治疗和远程 监测慢性缺血性伤口。获得专利的SmartMAEDS系统是一种创新方法， 结合ES和实时伤口监测。SmartMAEDS将降低成本并改善愈合 通过在绷带中提供治疗性ES来提高疗效，每次治疗都不需要重新定位 从而提高ES治疗的均匀性。SmartMAEDS还提供创新的远程监控 减少不必要的换药。通过评估伤口床阻抗，SmartMAEDS将 监测愈合的进展。SmartMAEDS还将通过监测来检查感染的早期迹象 伤口床温度。 Smart MAEDS系统的开发将包括对一次性柔性基板和 可重复使用的刺激/控制模块。我们在Koronis生物医学技术公司的合作者将开发两种 管理SmartMAEDS无线通信的软件应用程序。StimCheck将在后台运行 提供关于连接状态的即时反馈。StimMANAGE将为真实的 伤口状态的时间监测，包括图形历史和趋势，使临床医生能够控制和 根据需要调整治疗。我们将在猪缺血性伤口模型中评价SmartMAEDS， 相关尺寸在我们的初步工作中，ES范例显示出增强愈合和减少感染， 评估。定量非破坏性体内评估方法将包括监测组织 使用经皮血气水平和连续3D数字 摄影.将使用组织学、组织形态计量学， 免疫组织化学和RT-PCR来确定参与所有阶段的80多个基因的表达。 伤口愈合浮游细菌感染状况、生物膜形成和微生物群落分析将 也可以按照我们以前工作中制定的协议进行评估。 SmartMAEDS设备原型已在高级平台技术中心开发 质量体系/设计控制程序。多学科临床专家评审小组将确保这一点， 慢性伤口治疗的新方法将被临床用户高度接受。的有效治疗方法 慢性伤口是为退伍军人提供最高标准的医疗保健不可或缺的。翻译前 使用有效的动物模型对SmartMAEDS进行临床评价将为有效的 转化为临床护理。我们与Koronis Biomedical Technologies的合作将为上市前提供支持 开发一种使用方便的绷带，可佩戴长达五天，同时提供治疗 并监测伤口状况SmartMAEDS将成为伤口护理领域的颠覆性价值驱动技术 VHA以更低的成本向市场提供更多的临床受益，为患有慢性伤口的退伍军人提供更多的临床受益。

Non-healing ischemic wounds are a major problem for Veterans with physical impairment and/or disability. These chronic wounds cause significant pain and disability and occur at an alarmingly high frequency in at-risk Veteran populations cared for by the Veterans Healthcare Administration (VHA). The use of electrical stimulation (ES) for ischemic wound therapy has long been known but the outcomes have been variable. In previous work we developed an untethered electronic bandage with all the components of a surface stimulation system mounted on a flexible substrate. We systematically investigated the effects of a range of clinically relevant ES and found two paradigms that significantly enhanced healing in a rat ischemic wound model. One of these paradigms was also found to significantly reduce wound infection in an acute preclinical model of clinically relevant large wounds. The project will provide translational development and testing in a relevant large animal model of the Smart Modular Adaptive Electrotherapy Delivery System (SmartMAEDS) to provide both treatment and remote monitoring of chronic ischemic wounds. The patented SmartMAEDS system is an innovative approach incorporating both ES and real-time wound monitoring. SmartMAEDS will reduce cost and improve healing efficacy by providing therapeutic ES in a bandage that does not need to be repositioned for each treatment session thus improving uniformity of ES therapy. SmartMAEDS also provides innovative remote monitoring capabilities to reduce unnecessary dressing changes. By assessing wound bed impedance, SmartMAEDS will monitor progress towards healing. SmartMAEDS will also check for early indications of infection by monitoring wound bed temperature. Development of the Smart MAEDS system will include refinement of the disposable flexible substrate and the reusable stimulation/control module. Our collaborators at Koronis Biomedical Technologies will develop two software applications to manage SmartMAEDS wireless communication. StimCheck will run in the background providing instant feedback on connection status. StimMANAGE will provide a clinical user interface for real time monitoring of wound status including graphical history and trends, enabling the clinician to control and modify therapy as needed. We will evaluate SmartMAEDS in a pig model of ischemic wounds of a clinically relevant size. ES paradigms shown to enhance healing and reduce infection in our preliminary work will be assessed. Quantitative non-destructive in vivo assessment methodologies will include monitoring of tissue ischemia and progressive wound healing using transcutaneous blood gas levels and serial 3D digital photography. Wound status at fixed timepoints will be evaluated using histology, histomorphometry, immunohistochemistry and rt-PCR to determine the expression of over 80 genes involved in all stages of wound healing. Planktonic bacterial infection status, biofilm formation and microbial community profiling will also be evaluated following protocols developed in our previous work. Prototype SmartMAEDS devices have been developed under the Advanced Platform Technology Center Quality Systems/Design Control-program. A multidisciplinary clinical expert review panel will ensure that this new approach to chronic wound therapy will be highly acceptable to clinical users. The effective treatment of chronic wounds is integral to providing the highest standards of health care for Veterans. Translational pre- clinical evaluation of SmartMAEDS using a valid animal model will provide a strong foundation for effective translation to clinical care. Our collaboration with Koronis Biomedical Technologies will support pre-market development of a user-friendly bandage that can be worn for up to five days, concurrently delivering treatment and monitoring wound status. SmartMAEDS will be a disruptive value-driven technology in the wound care market at lower cost to VHA providing increased clinical benefit for Veterans with chronic wounds.