Pre-Clinical Development of an Instrumented Trapezium Carpal Bone

此R21提案的目标是完成临床前开发和评估 能够测量拇指根部关节接触载荷的替换梯形(ITRapz)，建立 未来梯形关节成形术临床试验的严格性。晚期癌症的多种外科治疗 拇指腕掌(CMC)或斜方掌骨(TMC)关节的骨关节炎(OA)有很大的不同 而且不是最优的。TMC OA是一种退行性疾病，由于疼痛和关节功能丧失而导致显著的功能障碍 功能。在50岁以上的人群中，TMC OA的患病率至少为20%-25%，并在进入第80个十年时有所增加 当多达80%的人有疾病的证据时。斜方掌骨关节中的高力被认为是 影响骨性关节炎的发展和治疗的成功。然而，我们对联合载荷的理解是在 Hand仅限于来自数学模型的预测，这些预测尚未得到活体测量的验证。 用来测量关节接触负荷的定制植入物已经被开发出来，用于髋关节、膝盖和脊柱。 来自这些植入物的数据为关节功能提供了关键的洞察力，具有明显的直接好处 验证和改进肌肉骨骼模型，并为植入物设计者和 制造商。仪器化植入物还有可能为患者提供高度新颖的生物反馈 引导康复。基于我们对TMC形态和运动学的广泛和严谨的活体研究， 和其他内固定关节的成功记录，我们建议开发和验证一种临床前 仪器化梯形植入物，我们称之为iTRapz。在我们的首要目标中，我们将设计、制造和 验证有线iTRapz的概念验证。在目标2中，我们将在身体模型中使用 机器人肌肉骨骼模拟器。一旦我们实现了这些目标，我们将拥有一种高度创新的负载传感器 适合身体研究。鉴于需要对拇指关节成形术进行更严格的研究，这 单是成就本身就会产生重大影响。在目标3中，我们将开发一个感应式第一个原型 带电源和远程电控的iTRapz植入物。在目标3中，我们还将开始计划在体内实施 临床研究。在完成目标3后，我们将演示在体内测量拇指负载 日常生活活动是可行的，我们将发展必要的知识、技能和 支持制造适合临床实施的密封植入物的技术。这 该项目意义重大，因为它将使几个群体受益：临床医生将受益于 与疾病、损伤、手术和修复相关的负荷；建模和研究界将受益 直接通过测量日常生活活动中的关节载荷，而这些载荷是手头未知的；以及 工程师和制造商将从急需的性能数据中受益。

The goal of this R21 proposal is to complete the preclinical development and evaluation of an instrumented replacement trapezium (iTrapz) capable of measuring joint contact loads at the base of the thumb, establishing the rigor for a future clinical trial in trapezial arthroplasty. The numerous surgical treatments for late-stage osteoarthritis (OA) of the thumb carpometacarpal (CMC) – or trapeziometacarpal (TMC) – joint, are highly varied and suboptimal. TMC OA is a degenerative disease that results in significant impairment due to pain and loss of function. The prevalence of TMC OA is at least 20-25% in those over 50, and it increases into the eighth decade when as many as 80% have evidence of disease. High forces in the trapeziometacarpal joint are believed to influence OA development and treatment success. However, our understanding of joint loads developed in the hand is limited to predictions from mathematical models that have yet to be validated by in vivo measurements. Custom implants instrumented to measure joint contact loads have been developed for the hip, knee, and spine. Data from these implants has provided critical insight into joint function, with the tangible direct benefits of validating and improving musculoskeletal models and providing important information for implant designers and manufacturers. Instrumented implants also have the potential to provide highly novel biofeedback to patients to guide rehabilitation. Building on our extensive and rigorous in vivo studies of TMC morphology and kinematics, and the records of success in other instrumented joints, we propose to develop and validate a preclinical instrumented trapezium implant, which we refer to as the iTrapz. In our first aim we will design, fabricate and validate a proof-of-concept wired iTrapz. In Aim 2 we will validate the wired iTrapz in a cadaver model using a robotic musculoskeletal simulator. Once we complete these aims we will have a highly innovative load sensor suitable for cadaver studies. Given the need for more rigorous studies of thumb arthroplasties, this accomplishment alone will have a significant impact. In Aim 3 we will develop a first-prototype inductively powered and telemeterized iTrapz implant. In Aim 3 we will also begin planning for in vivo implementation in a clinical study. Upon completion of Aim 3 we will have demonstrated that measuring in vivo thumb loads during the activities of daily living is feasible, and we will have developed the necessary knowledge, skills and technologies to support the fabrication of a hermetically sealed implant suitable for clinical implementation. This project is significant in that it will benefit several constituencies: clinicians will benefit from the knowledge of the loads associated with disease, injury, surgery and repair; the modeling and research communities will benefit directly from measurements of joint loads during activities of daily living, which are unknown in the hand; and engineers and manufacturers will benefit from critically-needed performance data.