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 并不是真正治疗这种疾病。到目前为止，外科手术中最好的方法是使用替代性组织移植。 可以从相同的患者(即自体移植)或其他捐赠者(例如同种异体移植)获得或构建 通过组织工程学的方法。然而，这些替代移植物经常遭受机械故障和 长期的不稳定。他们中的许多人无法再生健康负荷所需的透明软骨- 有软骨组织的。关节载荷在关节运动过程中直接作用于软骨组织，发挥着重要的作用。 对于这种机械故障和替代软骨移植的再生能力具有重要作用。而当 关节力，超过一定范围，会损伤软骨，适当大小的力可以促进 损伤组织的愈合。尽管有大量证据表明联合加载的重要作用，但研究和 在活体条件下和临床上，机械刺激治疗骨性关节炎的应用非常有限。 设置。这一限制主要是由于缺乏关于直接施加的实际关节力的信息 活体关节运动过程中软骨移植的研究。因此，为了获得此类信息，需要 开发一种特殊的力传感器，它可以具有几种所需的功能和特性。首先，工具需要 超薄，可与替代软骨移植无缝结合，避免分离和 在植入过程中扰乱关节的复杂力学。其次，传感器应该是可生物吸收的 不干扰组织再生，避免任何侵入性切除手术，这将直接损害- 接合的软骨。最后，传感器可以提供对过程中的力的连续实时监测 活体关节运动。在这里，我们将首次研究设备-软骨接口之间的 压电式PLLA压力传感器和替代的自体软骨移植，两者一起可以监测 体内关节加载和修复软骨缺损。传感器系统将提供准确可靠的 有关关节载荷的信息，可用于跟踪与软骨力相关的骨关节炎的演变/原因 最终，与物理疗法或其他机械刺激相结合，产生最佳的关节力 以获得体内最好的软骨再生。传感器随后将自我降解，促进组织内长和 避免任何侵入性的摘除手术。因此，我们的建议有两个具体目标。目标1是评估 可生物降解聚乳酸传感器的功能寿命、降解曲线和性能 体外模拟关节载荷的测量。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，并展示传感器的可靠性，以无线方式实时测量关节- 在活体内装载。

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.