Overcoming Complications of Polypropylene Prolapse Meshes: Development of Novel Elastomeric Auxetic Devices

项目摘要 盆腔器官脱垂（POP）是一种常见的，昂贵的条件，在妇女与手术修复的终身风险， 百分之十二点六在接受自体组织修复的患者中，40%的患者在2年内会失败，这促使外科医生转向 生物材料，最常见的是聚丙烯网片。不幸的是，POP补片是腹部疝补片 在510 K应用程序下重新销售用于POP修复，因此从未专门设计 为了阴道我们的研究表明，植入聚丙烯补片会导致变性、萎缩 以及阴道功能丧失。聚丙烯的高材料刚度决定了补片 由这种聚合物制成的针织物，导致经历孔塌陷、扭曲和变形的装置， 永久变形-所有这些都导致补片负荷增加，异物反应加剧， 可怜的结果。我们假设由弹性聚合物和材料制成的补片 硬度与阴道的硬度在同一数量级，有利于稳定毛孔的几何形状， 最小的张拉变形将与更有利的主机响应相关联， 现有聚丙烯脱垂补片。在这里，我们建议开发和评估一个网格 由聚碳酸酯-聚氨酯（PCU）合成，PCU是一种弹性体，其固有刚度与 但其也足够坚韧以满足生理负载需求。补片设计为 拉胀孔隙;这意味着它们随着负载而膨胀而不是收缩。此外，该网可以3D打印， 允许我们微调平面内几何形状和厚度，并允许非旋转结，从而 减少了翘曲和永久变形。具体地说，我们在这个应用程序中的目标是描绘 我们对PCU刚度的选择对主机对网格的响应的影响，因为这种选择会影响 达到结构支撑和强度所需材料量与聚丙烯相当 网格物质的量直接影响宿主反应的大小，但也可能影响宿主的反应。 或增强反馈到宿主响应中的装置中的机械行为，例如，颤动。因此在 为了使这种设备最终用于人类，我们将研究我们的设计选择如何独立地进行， 通过以下方式影响宿主对补片材料和力学的反应：（目的1）植入小单位的 具有不同材料刚度、纤维宽度和网片厚度的网片在阴道上无张力， 载荷，以及（目标2）利用计算建模和离体测试来确定相同的影响 设计选择的机械行为的全长网与负载。在目标3中，我们将研究如何 平衡主体对材料的反应与网格力学产生的反应的选择 共同促成了对通过骶骨阴道固定术在张力下植入的网状物的总体宿主反应， 与传统聚丙烯补片相比，经验证的动物模型。通过这种方式， 在这项提议中，有很大的潜力显著改善POP手术修复的结果。

PROJECT SUMMARY Pelvic organ prolapse (POP) is a common, costly condition in women with a lifetime risk of surgical repair of 12.6%. Of those undergoing a native tissue repair, 40% will fail by 2 years prompting surgeons to turn to biomaterials, most commonly polypropylene mesh. Unfortunately, POP meshes are abdominal hernia meshes that have been remarketed under 510K applications for POP repair and, thus, were never designed specifically for the vagina. Our studies show that implantation with polypropylene mesh leads to degeneration, atrophy and loss of function of the vagina. The high material stiffness of polypropylene dictates that meshes manufactured from this polymer are knitted, leading to a device that undergoes pore collapse, wrinkling, and permanent deformation -- all contributing to increased mesh burden, a heightened foreign body response, and poor outcomes. We hypothesize that a mesh generated from an elastomeric polymer with a material stiffness on the same order of magnitude as that of the vagina, a geometry that favors stable pores, and minimal wrinkling with tensioning will be associated with a more favorable host response than current polypropylene prolapse meshes. Here we are proposing to develop and evaluate a mesh synthesized from polycarbonate-urethane (PCU), an elastomer with an inherent stiffness similar to that of vagina but that is also sufficiently tough to meet physiologic loading demands. The mesh is designed with auxetic pores; meaning they expand instead of contract with loading. In addition, the mesh can be 3D printed, permitting us to fine tune the in-plane geometry and thickness, and allow for non-rotational junctions, thereby reducing wrinkling and permanent deformation. Specifically, our goal in this application is to delineate the impact of our choice for the stiffness of PCU on the host response to the mesh because this choice will impact the amount of material necessary to achieve structural support and strength equivalent to that of polypropylene mesh. The amount of material contributes directly to the magnitude of the host response, but can also obviate or enhance mechanical behaviors, e.g. wrinkling, in the device that feedback into the host response. Thus, in moving this device forward for eventual use in humans, we will study how our design choices independently impact the host response to the material and the mechanics of the mesh by: (Aim 1) implanting small units of the mesh with varied material stiffness, fiber width and mesh thickness on the vagina without tensioning and loading, and (Aim 2) utilizing computational modeling and ex vivo tests to determine the impact of the same design choices on the mechanical behavior of the full length mesh with loading. In Aim 3, we will study how choices that balance the host response to the material with those resulting from the mechanics of the mesh collectively contribute to the overall host response to a mesh that is implanted on tension by sacrocolpopexy in a validated animal model as compared to conventional polypropylene mesh. In this way, the device developed in this proposal has high potential for markedly improving outcomes in POP surgical repair.