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.

截肢患者通常会使用基于关节窝的系统，通过摩擦力来稳定 接受腔与残肢软组织的接触。尽管提供了先进的护理， 在VA医疗保健系统截肢的患者中，许多人放弃了传统的基于插座的系统。 在一项对与战斗有关的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， 女性的比例最高。为了改善这些患者的功能和生活质量， 经皮骨整合（OI）对接系统正在世界范围内开发。 OI的概念是基于活骨细胞附着在钛表面的能力， 几十年来，将普通的牙科和矫形装置锚到活骨上。我的研究把我带到了 这个范式。我设计了经皮OI设备，需要连接一个承重金属柱， OI内假体，永久穿过皮肤连接到远端外假体 身体外的组件。迄今为止，FDA尚未批准经皮OI器械的广泛使用 在美国境内。不幸的是，几种OI装置已经被实验性地放置到患者体内， 使用未经授权的欧洲设计复制品或使用未经证实的设备修改的其他团体 标签外使用。未经FDA批准，经皮OI技术的广泛商业引入受到限制， 所有的医疗系统。 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 失去了肢体为了实现这一目标，我们需要将安全的、FDA批准的经皮OI设备带到这个值得关注的领域。 患者人群。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器械的方法。我们遵循严格的科学方法， 实现FDA批准在美国各地使用的目标。我的临床前工作从基本的 台式科学到大量的动物模型试验，调查的基本原则，不仅骨骼固定， 也防止了在经皮柱穿过皮肤时产生的造口处的感染。这些预- 临床研究发现，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 最初的外科手术，制造适当的手术器械，测试最初的生物力学 稳定性，并建立了器械的静态力学和疲劳性能。这项临床前工作最终 批准首个FDA指导的经皮OI器械在10人人群中的早期可行性研究（EFS） 做过股骨截肢手术的退伍军人通过经股动脉EFS获得的信息现在用于 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，我已经扩大了我的努力，为患者提供经股动脉截肢，因为他们的深刻 使用传统外假体的功能损失和困难。我们正在完成临床前开发 建立初始手术程序，制造适当的手术工具，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 进行一次跨季节的EFS。虽然主要目的是对经皮OI进行FDA指导的EFS 用于经肱骨截肢患者的对接系统，确定其初始安全性，次要目的是 使用以患者为中心的方法来量化OI器械对靶肌肉的功能有效性 重新支配神经来控制外装假体通过transshumeral 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。