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

克服聚丙烯脱垂网的并发症：新型弹性拉胀装置的开发

基本信息

批准号：
10372098
负责人：
STEVEN D ABRAMOWITCH
金额：
$ 49.91万
依托单位：
MAGEE-WOMEN'S RES INST AND FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-17 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10372098
关键词：
3D Print Age Animal Model Atrophic Behavior Biocompatible Materials Complex Computer Analysis Computer Models Contracts Development Device Designs Devices Disadvantaged Elastomers Epithelial Equilibrium Experimental Models FDA approved Feedback Fiber Fibrosis Foreign Bodies Geometry Goals Hernia Hernia of abdominal cavity Human Immune response Implant Length Litigation Mechanics Modeling Operative Surgical Procedures Oryctolagus cuniculus Outcome Pain Periodicity Physiological Plague Play Polymers Polypropylenes Porosity Primates Ptosis Role Stress Surgeon Surgical Mesh Surgical sutures Technology Testing Thick Tissues United States Urethane Vagina Width Woman base cost design elastomeric flexibility functional loss implantation improved outcome in vivo lifetime risk loss of function mechanical behavior novel pelvic organ prolapse polycarbonate predictive modeling preservation prototype repaired response surgery outcome surgical risk tissue repair

项目摘要

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.

项目概要盆腔器官脱垂 (POP) 是女性常见且昂贵的疾病，终生都有手术修复的风险 12.6%。在接受原生组织修复的患者中，40% 会在 2 年后失败，这促使外科医生转向生物材料，最常见的是聚丙烯网。不幸的是，POP 补片是腹部疝气补片已在 510K POP 修复应用下重新上市，因此从未专门设计对于阴道。我们的研究表明，植入聚丙烯网会导致变性、萎缩和阴道功能丧失。聚丙烯的高材料刚度决定了网格用这种聚合物制成的材料被编织而成，从而形成一种会发生孔隙塌陷、起皱和变形的装置。永久变形——所有这些都会导致网片负担增加、异物反应增强，以及结果不佳。我们假设由弹性聚合物和材料生成的网格硬度与阴道的硬度处于同一数量级，这种几何形状有利于稳定的毛孔，与张力相比，最小的皱纹将与更有利的宿主反应相关目前的聚丙烯脱垂网。在这里，我们建议开发和评估网格由聚碳酸酯-聚氨酯 (PCU) 合成，这是一种固有刚度类似于的弹性体阴道，但也足够坚韧以满足生理负荷需求。网格设计为拉胀毛孔；这意味着它们在加载时会膨胀而不是收缩。此外，网格可以进行3D打印，允许我们微调面内几何形状和厚度，并允许非旋转连接，从而减少皱纹和永久变形。具体来说，我们在此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，因为此选择会影响达到与聚丙烯相当的结构支撑和强度所需的材料量网。材料的量直接影响宿主响应的大小，但也可以避免或增强机械行为，例如起皱，在设备中反馈到主机响应中。因此，在为了将该设备最终用于人类，我们将研究我们的设计选择如何独立通过以下方式影响宿主对材料和网格力学的响应：（目标 1）植入小单元将具有不同材料刚度、纤维宽度和网状厚度的网状材料置于阴道上，无需张紧和加载，以及（目标 2）利用计算模型和离体测试来确定相同的影响全长网格在加载时的机械行为的设计选择。在目标 3 中，我们将研究如何平衡主体对材料的响应与网格力学产生的响应的选择共同促进宿主对通过骶骨阴道固定术在张力下植入的网状物的总体反应与传统聚丙烯网相比，这是一种经过验证的动物模型。就这样，该装置研制成功该提案具有显着改善 POP 手术修复结果的巨大潜力。