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

 描述(申请人提供)：创伤和过度使用关节会导致关节软骨和底层骨的疼痛缺陷，从而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，这种早期损害可能会扩散，导致终末期骨关节炎(OA)。虽然骨软骨缺失的治疗方法已经被开发出来，以缓解疼痛和延缓损伤的扩散，但目前的解决方案被认为是不可靠的-需要及早手术修复。为了更好地治疗这些缺陷，我们开发了一种创新的不可降解的现成设备，该设备将在植入过程中立即为缺失部位提供结构完整性，同时还与宿主组织整合。该装置是基于非细胞的、不可生物降解的、人工合成的和多孔的，因此代表着目前治疗软骨和骨软骨缺陷的范例的重大转变。该植入物由一个坚固的圆柱形聚乙烯醇(PVA)核心(用于抵抗关节负荷)组成，由一个多孔的PVA外圈(与周围组织压配合并设计为与软骨结合)同心包围，该固体核心附着在一个多孔的金属底座上(用于初始固定和与骨的结合)。该装置在关节镜下以脱水的形式植入支架内，然后在原位重新水化，与宿主组织形成牢固的界面，从而能够立即负重。虽然一系列体外和体内动物模型已经证明，该装置可以与宿主组织结合，并以自然组织的方式发挥机械功能，但我们遇到了几例PVA与金属基底分离时装置发生机械故障的情况。这项研究的目的是修改PVA-金属界面，以防止故障，同时保持该设备在加载的关节中机械运行的能力。为此，我们使用有限元模型来直接修改：(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联锁和PVA硬度(总共15组)中的哪一种组合足够坚固，能够承受持续的负重。首先，我们将优化PVA-金属界面的剪切和拉伸强度，以避免设备复水后的机械故障(具体目标1)。其次，我们将使用定制的滚动-滑动设备在现场模拟施加到设备上的力(特定目标2)，使设备承受重复的轴向力和剪切力。优化设计标准将基于在有限元模型(目标1)中计算的PVA-金属界面处的最大剪应力和拉应力，以及疲劳性能的表征 设备(目标2)。通过这套测试，我们将确定具有最高剪切和拉伸安全系数的设备设计，该设备能够在延长的加载循环中恢复连接上的负载分布。这项研究的优化设计将随后用于重新植入我们先前建立的活体马模型。

 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.