RR&D Research Career Scientist Award Application

截肢患者通常会被提供基于插座的系统，这些系统通过摩擦来稳定 关节窝与残肢软组织之间的接触。尽管提供了尖端的护理， VA Healthcare System截肢的患者中，许多人放弃了传统的基于插座的系统。 在一项对与战斗相关的单侧上肢丧失的退伍军人进行的研究中，25%的退伍军人放弃了他们的牙槽窝- 以假肢为基础的，女性中的比例最高。为了改善这些患者的功能和生活质量， 经皮骨整合(OI)对接系统正在全球范围内开发。 OI的概念是基于活的骨细胞附着在钛表面的能力，并已被使用 几十年来，将常见的牙科和矫形设备固定在活骨上。我的研究把我带到了外面 这是一种范例。我设计了经皮输液设备，它需要一个承重的金属柱连接到 OI内假体，永久通过皮肤连接到远端外假体 身体外的成分。到目前为止，FDA还没有批准经皮OI设备的广泛使用 在美国境内。不幸的是，几个OI设备已经被试验性地放置到患者体内 其他使用未经授权的欧洲设计复制品或未经证实的设备改装的组织 标签外。在没有FDA批准的情况下，经皮OI技术的广泛商业引入受到限制 所有的医疗系统。 我的研究的首要目标是最大限度地提高美国退伍军人的功能恢复和生活质量 失去四肢。为了实现这一点，我们需要将安全的、FDA批准的经皮OI设备带到这个应得的 病人群体。自2006年以来，我一直领导一个多学科团队的工程工作，该团队使用数据驱动的 为截肢者设计经皮OI装置的方法。我们遵循了严格的科学方法， 实现FDA批准在全美使用的目标。我的临床前工作从基础工作到 大量动物模型试验的台式科学，不仅研究骨骼固定的基本原理，而且 此外，在经皮穿刺桩通过皮肤时，可防止造口感染。有了这些前- 临床表现，我们设计和制造了一系列经股动脉经皮OI装置，我们建立了 最初的手术程序，制造了适当的手术器械，测试了最初的生物力学 稳定性，并建立了该装置的静态力学和疲劳性能。这项临床前的工作达到了顶峰 批准FDA指导的第一项经皮OI装置的早期可行性研究(EFS)，该研究在10人中进行 接受股动脉截肢的退伍军人。通过经股动脉EFS获得的信息现在被用于 过渡到FDA批准的多中心关键临床试验和广泛的临床采用。 自2014年以来，我一直在扩大我的努力，为经胸截肢患者服务，因为他们的 使用传统外假体时的功能损失和困难。我们正在完成临床前开发 建立初始手术程序，制造适当的手术器械，测试 初始生物力学稳定性，并完成提交FDA审议的设计历史文件 进行经胸腔内的EFS。虽然主要目的是在FDA的指导下进行经皮OI的EFS 经胸截肢患者的对接系统，建立其最初的安全性，次要目标是 使用以患者为中心的方法来量化具有靶向肌肉的OI装置的功能有效性 再神经支配来控制外假体。通过经胸EFS获得的信息将被用来帮助 过渡到FDA批准的多中心关键临床试验和广泛的临床采用。

Patients with amputated limbs are customarily offered socket-based systems, which are stabilized by friction contact between the socket and the soft tissues of the residual limb. Despite the leading-edge care provided to patients with amputations by the VA Healthcare System, many abandon their conventional socket-based systems. In a study of veterans with combat-associated unilateral upper-limb loss, 25% of veterans abandon their socket- based prosthetics, with rates highest among women. To improve function and quality of life for these patients, percutaneous osseointegrated (OI) docking systems are being developed worldwide. The concept of OI is based on the ability of living bone cells to attach to a titanium surface and has been used for decades to anchor common dental and orthopaedic devices to living bone. My research takes me outside this paradigm. I engineer percutaneous OI devices, which require a load-bearing metal post to be connected to the OI endoprosthesis, passing permanently through the skin to be connected to the distal exoprosthetic componentry outside of the body. To date, the FDA has not approved the broad use of percutaneous OI devices within the United States. Unfortunately, several OI devices have been experimentally placed into patients by other groups using either unauthorized copies of European designs or using unproven modifications of devices off-label. Without FDA approval, the broad commercial introduction of percutaneous OI technology is limited in all healthcare systems. The overarching goal of my research is to maximize the functional recovery and the quality of life of US Veterans with limb loss. To achieve this, we need to bring safe, FDA approved percutaneous OI devices to this deserving patient population. Since 2006, I have led the engineering efforts of a multidisciplinary team that uses a data-driven approach to engineer percutaneous OI devices for amputees. We have followed a strict scientific approach with the goal of achieving FDA approval for use throughout the United States. My pre-clinical work ranged from basic bench-top science to numerous animal model trials, investigating basic principles of not only skeletal fixation, but also infection prevention at the stoma created as the percutaneous post passes through the skin. With these pre- clinical findings, we designed and manufactured a series of transfemoral percutaneous OI devices, we established the initial surgical procedures, manufactured appropriate surgical instrumentation, tested the initial biomechanical stability, and established the static mechanics and fatigue properties of the device. This pre-clinical work culminated in approval of the first FDA directed Early Feasibility Study (EFS) of a percutaneous OI device in a population of 10 veterans with transfemoral amputations. Information obtained via the transfemoral EFS is now being used to transition to a multicenter pivotal clinical trial for FDA approval and wide-range clinical adoption. Since 2014, I have expanded my efforts to serve patients with transhumeral amputations because of their profound functional losses and difficulties using conventional exoprostheses. We are completing the preclinical development of this device, establishing the initial surgical procedures, manufacturing appropriate surgical instrumentation, testing the initial biomechanical stability, and completing the design history file for submission to the FDA for consideration to conduct a transhumeral EFS. While the Primary Aim is to perform an FDA guided EFS of a percutaneous OI docking system for patients with transhumeral amputations, establishing its initial safety, the Secondary Aim is to use a patient-centered approach to quantify the functional effectiveness of the OI device with targeted muscle re-innervation to control the exoprosthesis. Information obtained via the transhumeral EFS will be used to help to transition to a multicenter pivotal clinical trial for FDA approval and wide-range clinical adoption.