Compliant Limb Reconstruction: Co-engineering Body and Machine to Revolutionize Limb Salvage

项目总结 我的长期目标是重建因受伤或疾病而失去功能的肢体。为了实现这一目标， 我的研究项目将外科手术和机械设计结合在一个叫做解剖学的范例中，在这个范例中，身体 和机器共同设计，追求卓越的仿生性能。在这项提议中，我应用了解剖学- 四肢病变外科治疗的中心进路。人体是由顺从的 (“灵活的”)结构是基本功能的基础。连接的高度柔顺的结构--接头 骨骼结合在一起，可能是这些结构中对人类运动最重要的。细微差别 关节组织中的载荷和变形之间的关系(称为“顺应性”)决定了关节组织的内部和外部环境。 外力转换为肢体运动。破坏固有的生物顺应性往往是毁灭性的 身体以健康的方式移动的能力。这种中断可能是由于受伤或疾病，甚至是 旨在减轻肢体病理的重建手术。在严重的情况下，疼痛和残疾造成的 由于肢体顺应性的变化如此剧烈，治疗选择如此有限，以至于患者选择截肢 他们有生存能力但功能失调的四肢在寻求解脱。不幸的是，目前还没有办法纠正 生物关节和组织在受到破坏时的遵从性；这给 越来越多的四肢病变患者，他们经常被留下来生活在有生存能力但不是 功能齐全。为了回应这种需求，我提出了一种新型的顺应性可植入假体，它将 使病理关节顺应性得到纠正，功能恢复。在新创新者的支持下 奖，我将提出一种新的顺应性肢体重建(CLR)管道，能够产生关节和- 病理特定的植入物机制，并应用该管道为两种肢体病变设计植入物 紧急的未得到满足的临床需求。然后我将制造和验证这些植入物，收集关键数据来支持 人类受试者的早期可行性研究。这项工作将为未来的计划奠定基础 CLR管道的改进，是迈向使用该方法进行目标的研究计划的第一步 身体所有的关节都有许多不同的病理。我预计拟议的研究将改变 肢体病理治疗的临床范例，为革命性的新抢救选择打开了大门 减轻疼痛，恢复功能，防止截肢。

PROJECT SUMMARY My long-term goal is to reconstruct limbs that have lost function due to injury or disease. To achieve this goal, my research program combines surgical and mechanical design in a paradigm called anatomics, in which body and machine are co-engineered in pursuit of superior bionic performance. In this proposal, I apply an anatomics- centered approach to the surgical treatment of limb pathology. The human body is made up of compliant (“flexible”) structures that are fundamental to basic function. Joints, the highly-compliant structures that link bones together, are perhaps the most important of these structures for human movement. The nuanced relationships between load and deformation (called “compliance”) in joint tissues dictate how internal and external forces are converted to limb motion. Disruption of inherent biological compliance is often devastating to the body’s ability to move in a healthy way. This disruption can occur as a result of injury or disease, or even the reconstructive procedures intended to alleviate limb pathology. In severe cases, the pain and disability caused by changes to limb compliance are so intense, and treatment options so limited, that patients choose to amputate their viable but dysfunctional limb in search of relief. Unfortunately, there is currently no way to correct the compliance of biological joints and tissues when they are disrupted; this creates enormous challenges for the increasing number of patients with limb pathology, who are often left to live with limbs that are viable but non- functional. In response to this need, I propose a novel class of compliant implantable prostheses that would enable pathological joint compliance to be corrected, and function restored. With support from the New Innovator Award, I will advance a novel compliant limb reconstruction (CLR) pipeline capable of generating joint-and- pathology-specific implant mechanics, and apply this pipeline to design implants for two limb pathologies with urgent unmet clinical needs. I will then fabricate and validate these implants, collecting critical data to support early feasibility studies in human subjects. This work will form the foundation for future initiatives supporting refinement of the CLR pipeline, and is the first step toward a research program that uses the approach to target many different pathologies across all of the body’s joints. I expect that the proposed research will transform the clinical paradigm for treatment of limb pathology, opening the door to revolutionary new salvage options that alleviate pain, restore function, and prevent amputation.