Real-time measurement of joint-loading for osteoarthritis study and treatment

实时测量关节负荷，用于骨关节炎研究和治疗

• 批准号: 10359757
• 负责人: Thanh Nguyen
• 金额: $ 21.18万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10359757
• 关键词: American; Anatomy; Animals; Autologous Transplantation; Benchmarking; Cartilage; Cells; Chondrogenesis; Clinical; Complex; Defect; Degenerative polyarthritis; Devices; Disease; Engineering; Evolution; Excision; Exhibits; Failure; Film; Growth; Hyaline Cartilage; Implant; In Vitro; Joints; Knee; Leg; Life; Limb structure; Measurement; Measures; Mechanical Stimulation; Mechanics; Medical; Medicine; Methods; Monitor; Motion; Natural regeneration; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Patients; Performance; Physical Exercise; Physical therapy; Play; Polymers; Process; Property; Reporting; Role; Surgical sutures; System; Theoretical model; Time; Tissue Engineering; Tissue Grafts; Tissues; Variant; Weight-Bearing state; biomaterial compatibility; bone; cartilage regeneration; cartilage repair; cartilage transplantation; distraction; flexibility; force sensor; healing; implantation; implanted sensor; in vivo; in vivo monitoring; in vivo regeneration; individual patient; injured; innovation; instrument; joint loading; knee replacement arthroplasty; mechanical load; osteochondral tissue; patient population; pressure sensor; real time monitoring; reduce symptoms; regenerative; scaffold; sensor; stem; success; temporal measurement; tissue regeneration; tool; ultrasound; wireless; wireless sensor

Abstract Millions of American suffer from Osteoarthritis (OA) while available medicines only alleviate symptoms but do not actually treat this disease. Surgically, the golden method so far has been to use substitutive tissue grafts which can be obtained from the same patients (i.e. auto-grafts) or other donors (e.g. allo-grafts) or constructed by tissue-engineering approach. However, these replacement grafts often suffer from mechanical failures and long-term instability. Many of them fail to regenerate hyaline cartilages which are required for healthy load- bearing cartilage tissues. Joint-loading, directly applied on cartilage tissues during joint-motions, plays a significant role for such mechanical failures and regenerative capability of replacement cartilage grafts. While joint-force, beyond a certain range, damages the cartilages, the force with appropriate magnitudes can promote healing of injured tissues. Despite numerous evidences on the important role of joint-loading, studies and applications of mechanical stimulation for the treatment of OA are very limited in in vivo conditions and clinical settings. This limitation mainly stems from the lack of information about actual joint-force which is directly applied on replacement cartilage grafts during motion of joints in vivo. To obtain such information, it is thus needed to develop a special force sensor that can possess several desired functions and properties. First, the tools need to be ultrathin and can be seamlessly integrated with replacement cartilage grafts to avoid being detached and disturbing the joint’s complex mechanics during implantation. Second, the sensors should be bioresorbable to not interfere in tissue regeneration and avoid any invasive removal surgery, which would damage the directly- interfaced cartilages. And finally, the sensor can provide a continuous real-time monitoring of the force during joint motions in vivo. Here, we will study, for the first time, a device-cartilage interface between the piezoelectric PLLA pressure sensor and a replacement cartilage auto-graft, which together can monitor in vivo joint-loading and heal cartilage-defects. The sensor system will provide accurate and reliable information about joint-loading, which can be used to track OA-evolution/cause in relation with cartilage-force and ultimately, combined with physical therapy or other mechanical stimulations to induce an optimal joint-force for the best cartilage regeneration in vivo. The sensor will be then self-degraded, facilitating tissue ingrowth and avoiding any invasive removal surgery. Accordingly, our proposal has two specific aims. Aim 1 is to assess functional lifetime, degradation profile and performance of the proposed biodegradable PLLA sensors for measuring simulated joint-loading in vitro. Aim 2 is to assess the healing of cartilage defects, receiving autografts integrated with the PLLA sensors and demonstrate reliability of the sensors to wirelessly measure real-time joint- loading in vivo.

抽象的 数以百万计的美国患有骨关节炎（OA）的患者虽然可用的药物仅减轻症状，但会减轻症状 实际上不是治疗这种疾病。从外科手术上，到目前为止的黄金方法是使用替代组织移植 可以从同一患者（即自动移植物）或其他捐助者（例如Allo-Grafts）或构造的患者获得 通过组织工程方法。但是，这些替代移植物通常会遭受机械故障的困扰和 长期不稳定。他们中的许多人未能再生健康负荷所需的透明软骨 - 轴承软骨组织。联合负载在关节运动过程中直接应用于软骨组织，播放A 这种机械故障和替代软骨移植物的再生能力的重要作用。尽管 联合力量超出一定范围，损坏了软骨，具有适当尺寸的力可以促进 受伤组织的愈合。尽管有许多关于联合负载，研究和 机械模拟在体内条件和临床上的应用非常有限 设置。该限制主要是由于缺乏直接应用的实际关节力量的信息 在体内运动过程中，在替换软骨移植物上。要获取此类信息，因此需要 开发一种特殊的力传感器，该传感器可以潜力几个所需的功能和特性。首先，工具需要 要成为超薄，并且可以与替换软骨移植物无缝集成以避免被脱落和 在植入过程中打扰关节的复杂力学。其次，传感器应可生物吸收到 不会中断组织再生并避免进行任何侵入性去除手术，这会损害直接的 接口软骨。最后，传感器可以在期间对力进行连续的实时监控 体内关节运动。在这里，我们将首次研究 压电PLLA压力传感器和替换软骨自动移植物可以一起监测 体内联合负载和治愈软骨缺失。传感器系统将提供准确可靠的 有关联合负载的信息，该信息可用于跟踪与软骨力有关的OA进化/原因 最终，结合物理疗法或其他机械刺激，诱导最佳关节力量 在体内最好的软骨再生。然后，传感器将被自降解，支撑组织inrowth和 避免进行任何侵入性去除手术。根据，我们的建议有两个具体的目标。目标1是评估 功能寿命，降解概况和提议的可生物降解PLLA传感器的性能 在体外测量模拟的联合负载。 AIM 2是评估软骨缺陷的愈合，接受自体移植 与PLLA传感器集成，并证明传感器可靠地测量实时关节的可靠性 在体内加载。