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

摘要 数以百万计的美国人患有骨关节炎（OA），而现有的药物只能缓解症状，但不能 而不是真正治疗这种疾病。在外科手术中，迄今为止最好的方法是使用替代组织移植物 其可以从相同的患者（即自体移植物）或其他供体（例如同种异体移植物）获得或构建 通过组织工程的方法。然而，这些替代移植物经常遭受机械故障， 长期不稳定。他们中的许多人无法再生健康负荷所需的透明软骨- 长着软骨组织关节运动时直接作用于软骨组织的关节负荷， 对于这种机械失效和替代软骨移植物的再生能力具有重要作用。而 关节力超过一定范围时，软骨会受到损伤，适当大小的力可以促进关节软骨的损伤 愈合受伤的组织。尽管有许多证据表明关节负荷的重要作用，研究和 用于治疗OA的机械刺激的应用在体内条件和临床上非常有限 设置.这种局限性主要源于缺乏直接应用的实际关节力的信息 在体内关节运动过程中对替代软骨移植物的影响。为了获得这些信息，需要 开发一种特殊的力传感器，可以拥有几个所需的功能和属性。首先，工具需要 可以与替代软骨移植物无缝结合，以避免分离， 在植入过程中干扰关节的复杂力学。第二，传感器应该是生物可吸收的， 不干扰组织再生，避免任何侵入性切除手术，这将直接损害- 连接的软骨最后，传感器可以提供连续的实时监测力， 体内的关节运动。在这里，我们将首次研究器械-软骨界面， 压电PLLA压力传感器和替代软骨自体移植物，它们一起可以监测 体内关节负荷和愈合软骨缺损。传感器系统将提供准确可靠的 关于关节负荷的信息，可用于跟踪与软骨力相关的OA演变/原因 并最终与物理治疗或其他机械刺激相结合以诱导最佳关节力 以获得体内最佳的软骨再生。然后传感器将自降解，促进组织向内生长， 避免任何侵入性的移除手术。因此，我们的建议有两个具体目标。目标1：评估 所提出的可生物降解PLLA传感器的功能寿命、降解曲线和性能， 测量体外模拟关节负荷。目的2是评估接受自体移植的软骨缺损的愈合情况 与PLLA传感器集成，并证明传感器的可靠性，以无线方式实时测量关节， 体内加载。

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.