Design Optimization of a Non-degradable Synthetic Device for Cartilage Defects

 描述（由申请人提供）：关节的创伤和过度使用可导致关节软骨和底层骨的疼痛性缺损，对整个关节的机械和生物功能产生不利影响。随着时间的推移，这种早期损伤可能会扩散，导致终末期骨关节炎（OA）。虽然骨软骨缺损的治疗方法已被开发用于缓解疼痛和延迟损伤的扩散，但目前的解决方案被认为是不可靠的-需要早期手术翻修。为了更好地治疗这些缺损，我们开发了一种创新的不可降解的现成器械，该器械将在植入期间为缺损部位提供即时的结构完整性，同时还与宿主组织整合。该器械是非细胞基的、不可生物降解的、合成的和多孔的，因此代表了当前治疗软骨和骨软骨缺损的范例的重大转变。植入物由实心圆柱形聚（乙烯）醇（PVA）芯（以抵抗关节载荷）和多孔PVA外缘（与周围组织压配并设计用于与软骨整合）同心包围组成，实心芯连接到多孔金属基底（用于初始固定和与骨整合）。该装置在关节镜下以脱水形式植入到缺损中，然后原位再水合以与宿主组织形成牢固的界面，从而能够立即承重。虽然一系列体外和体内动物模型已经证明该器械可以与宿主组织整合，并且在很大程度上以天然组织的方式发挥机械功能，但当PVA与金属基底分离时，我们遇到了几例器械机械失效的情况。本研究的目的是修改PVA-金属界面以防止失效，同时保持器械在负载关节中的机械功能。为此，我们使用有限元模型来指导修改：（i）PVA-金属界面的宏观几何形状，以及（ii）PVA-金属界面的刚度。我们的目标是确定宏观互锁和PVA刚度（共15组）变化的哪种组合足以承受持续承重。首先，我们将优化PVA-金属界面的剪切和拉伸强度，以避免器械再水化后的机械失效（具体目标1）。其次，我们将使用自定义滚动-滑动器械对器械施加重复的轴向力和剪切力，以模拟原位对器械施加的力（具体目标2）。优化设计标准将基于FE模型（目标1）中计算的PVA-金属界面处的最大剪切应力和拉伸应力，以及 器械（目标2）。通过这一系列测试，我们将确定具有最高剪切和拉伸安全系数的器械设计，该设计能够在延长的载荷循环中恢复整个关节的载荷分布。本研究的最佳设计随后将用于重新植入我们先前建立的体内马模型中。

 DESCRIPTION (provided by applicant): Trauma and overuse of joints can lead to painful defects in the articular cartilage and underlying bone, which adversely affect the mechanical and biological function of the entire joint. Over time this early-stage damage can spread, leading to end-stage osteoarthritis (OA). While treatments for osteochondral defects have been developed to relieve pain and delay the spread of damage, current solutions are perceived as unreliable - requiring early surgical revision. To better treat these defects, we have developed an innovative non- degradable, off-the-shelf device that will provide immediate structural integrity to the defec site for the duration of implantation, while also integrating with the host tissue. The device is non-cell based, non-biodegradable, synthetic and porous, and as such represents a significant shift in the current paradigm for the treatment of chondral and osteochondral defects. The implant consists of a solid cylindrical poly(vinyl) alcohol (PVA) core (to resist joint load) concentrically surrounded by a porous PVA outer rim (press-fit with surrounding tissue and designed to integrate with cartilage), with the solid core attached to a porous metal base (for initial fixation and integration with bone). The device is arthroscopically implanted into the defet in a dehydrated form, which then rehydrates in situ to form a strong interface with the host tissue, thus enabling immediate weight bearing. While a series of in vitro and in vivo animal models have demonstrated that the device can integrate with host tissue and mechanically function much in the way of the native tissue, we encountered several instances of mechanical failure of the device when the PVA disassociated from the metal base. The objective of this study is to modify the PVA-metal interface to prevent failures, while maintaining the ability of th device to mechanically function in a loaded joint. To this end we have used finite element models to direct modifications to: (i) the macroscopic geometry of the PVA-metal interface, and (ii) the stiffness of the PVA-metal interface. Our goal is to determine which combination of changes in macroscopic interlock, and PVA stiffness (15 groups in total) are robust enough to withstand sustained weight bearing. First, we will optimize the shear and tensile strengths of the PVA-metal interface to avoid mechanical failure after device rehydration (Specific Aim 1). Secondly, we will subject the device to repetitive axial and shear forces using a custom rolling-sliding device to simulate the forces applied to the device in situ (Specific Aim 2). Optimized design criteria will be based on the maximum shear and tensile stresses at the PVA-metal interface calculated in the FE model (Aim 1), and characterization of the fatigue properties of the device (Aim 2). Through this suite of tests, we will identify the device design with the highest shear and tensile safety factor that is able to restore load distribution across the joint over extended cycles of loading. The optimal design from this study will be subsequently used for re- implantation into our previously established in vivo horse model.