RR&D Research Career Scientist Award Application

RR

• 批准号: 10543085
• 负责人: Kent N. Bachus
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10543085
• 关键词: Adoption; Amputation; Amputees; Animal Model; Animals; Articular Range of Motion; Award; Biomechanics; Body Weight; Cadaver; Caring; Climacteric; Clinical; Clinical Trials; Commercial grade; Coupled; Data; Dental; Dental Prosthesis; Dermatitis; Device or Instrument Development; Devices; Distal; Docking; Effectiveness; Engineering; European; Event; FDA approved; Fatigue; Feasibility Studies; Femur; Fracture Fixation; Freezing; Friction; Gender; Goals; Handedness; Healthcare Systems; Heterotopic Ossification; Hip region structure; Human; Hyperhidrosis disorder; Implant; Infection prevention; Knee; Label; Left; Length; Measures; Mechanics; Metals; Modification; Monitoring Clinical Trials; Morphology; Motion; Multi-Institutional Clinical Trial; Operative Surgical Procedures; Orthopedics; Osseointegration; Pain; Patients; Population; Porosity; Positioning Attribute; Prevalence; Property; Prosthesis; Quality of life; Recording of previous events; Recovery of Function; Replacement Arthroplasty; Reporting; Research; Residual state; Safety; Science; Scientist; Series; Shoulder; Skin; Stomas; Surface; System; Technology; Testing; Titanium; Trauma; United States; Upper Extremity; Veterans; Weight-Bearing state; Woman; Work; battlefield injury; bone; bone cell; career; combat; daily functioning; design; experience; functional improvement; functional loss; humerus; instrumentation; limb amputation; limb loss; manufacture; morphometry; multidisciplinary; muscle reinnervation; novel; patient oriented; patient population; pre-clinical; preclinical development; professor; residual limb; soft tissue; stem

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.

通常为截肢患者提供基于插座的系统，该系统通过摩擦来稳定 接受腔与残肢软组织之间的接触。尽管提供了最先进的护理 退伍军人管理局医疗系统截肢的患者中，许多人放弃了传统的基于插座的系统。 在一项针对因战斗而导致单侧上肢丧失的退伍军人的研究中，25% 的退伍军人放弃了他们的关节窝 基于假肢的假肢，其中女性比例最高。为了改善这些患者的功能和生活质量， 世界范围内正在开发经皮骨整合（OI）对接系统。 OI 的概念基于活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骨科设备固定在活骨上。我的研究带我出去 这个范式。我设计了经皮 OI 设备，需要将承重金属柱连接到 OI内置假体，永久穿过皮肤连接到远端外假体 身体外部的组成部分。迄今为止，FDA 尚未批准经皮 OI 装置的广泛使用 在美国境内。不幸的是，一些 OI 设备已被实验性地植入患者体内 其他团体使用未经授权的欧洲设计副本或使用未经证实的设备修改 标签外。未经 FDA 批准，经皮 OI 技术的广泛商业推广仅限于 所有医疗保健系统。 我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 伴有肢体丧失。为了实现这一目标，我们需要将安全的、经 FDA 批准的经皮 OI 设备带到这个值得关注的领域。 患者群体。自 2006 年以来，我领导了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。我们遵循严格的科学方法 目标是获得 FDA 批准在美国各地使用。我的临床前工作范围从基础 将台式科学应用于大量动物模型试验，不仅研究骨骼固定的基本原理，而且研究 还可以预防经皮柱穿过皮肤时产生的造口处的感染。有了这些预 临床发现，我们设计并制造了一系列经股经皮 OI 装置，我们建立了 最初的手术程序，制造适当的手术器械，测试最初的生物力学 稳定性，并建立了装置的静态力学和疲劳性能。这项临床前工作达到了顶峰 批准第一项 FDA 指导的经皮 OI 装置针对 10 人的早期可行性研究 (EFS) 接受股骨截肢的退伍军人。通过经股 EFS 获得的信息现在被用于 过渡到多中心关键临床试验以获得 FDA 批准和广泛的临床采用。 自 2014 年以来，我加大了为经肱骨截肢患者提供服务的力度，因为它们对患者的影响深远 使用传统外假体的功能丧失和困难。我们正在完成临床前开发 该设备，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，并完成设计历史文件提交给 FDA 考虑 进行经肱骨 EFS。虽然主要目标是对经皮 OI 进行 FDA 指导的 EFS 经肱骨截肢患者的对接系统，建立其初步安全性，次要目标是 使用以患者为中心的方法来量化 OI 设备针对目标肌肉的功能有效性 重新神经支配以控制外假体。通过经肱骨 EFS 获得的信息将用于帮助 过渡到多中心关键临床试验以获得 FDA 批准和广泛的临床采用。