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

• 批准号: 10613362
• 负责人: STEVEN D ABRAMOWITCH
• 金额: $ 45.27万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-17 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10613362
• 关键词: 3D Print; Age; Animal Model; Atrophic; Behavior; Biocompatible Materials; Complex; Computer Analysis; Computer Models; Contracts; Development; Device Designs; Devices; Disadvantaged; Elastomers; Epithelium; Equilibrium; Experimental Models; FDA approved; Feedback; Fiber; Fibrosis; Foreign Bodies; Geometry; Goals; Hernia; Hernia of abdominal cavity; Human; Immune response; Implant; Length; Litigation; Marketing; Mechanics; Modeling; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Pain; Physiological; Play; Polymers; Polypropylenes; Porosity; Primates; Ptosis; Role; Stress; Surgeon; Surgical Mesh; Surgical sutures; Technology; Testing; Thick; Tissues; United States; Urethane; Vagina; Width; Woman; cost; design; elastomeric; flexibility; functional loss; implantation; improved outcome; in vivo; lifetime risk; loss of function; manufacture; mechanical behavior; novel; pelvic organ prolapse; polycarbonate; predictive modeling; preservation; prototype; repaired; response; surgery outcome; surgical risk; tissue repair

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.

项目总结 盆腔器官脱垂(POP)是一种常见的、代价高昂的疾病，女性一生都有可能接受手术修复 12.6%。在那些接受自然组织修复的人中，40%的人在两年内会失败，这促使外科医生转向 生物材料，最常见的是聚丙烯网状物。不幸的是，POP网片是腹股沟网片。 在510K POP修复申请中已经被注意到了，因此从来没有专门设计过 用在阴道上。我们的研究表明，植入聚丙烯网会导致变性、萎缩 以及阴道功能的丧失。聚丙烯的高材料硬度决定了网状结构 用这种聚合物制造的是针织的，导致设备经历毛孔坍塌，起皱，和 永久性变形--所有这些都会增加网眼负担，增强异物反应，以及 糟糕的结果。我们假设由弹性聚合物和一种材料生成的网格 硬度与阴道的硬度相同，这是一种有利于稳定毛孔的几何形状， 拉伸产生的最小皱纹将与更有利的宿主反应相关联 目前的聚丙烯脱垂网眼。在这里，我们建议开发和评估一个网状结构 由聚碳酸酯-氨基甲酸酯(PCU)合成的弹性体，其固有硬度与 但阴道也足够坚硬，以满足生理负荷要求。网格是用来设计的 扩张的毛孔；意味着它们会扩张，而不是随着负荷的收缩。此外，网格还可以进行3D打印， 允许我们微调平面内的几何形状和厚度，并允许非旋转连接，从而 减少起皱和永久变形。具体地说，我们在此应用程序中的目标是描述 我们对PCU刚度的选择对宿主对网格的响应的影响，因为此选择将影响 达到与聚丙烯相同的结构支撑力和强度所需的材料量 网状。材料的数量直接影响寄主反应的大小，但也可以避免 或增强设备中反馈到主机响应的机械行为，例如起皱。因此，在 将这一设备用于人类，我们将研究我们的设计是如何独立选择的 通过以下方式影响宿主对材料和网状结构的反应：(目标1)植入小单位的 具有不同材料硬度、纤维宽度和网眼厚度的网片在阴道上不张紧和 加载，以及(目标2)利用计算建模和体外试验来确定相同的影响 载荷作用下的全长网格力学行为的设计选择。在目标3中，我们将研究如何 选择平衡宿主对材质的响应和网格力学产生的响应 共同促进宿主对通过骶骨固定术植入张力的网状物的总体反应 一个经过验证的动物模型，与传统的聚丙烯网状物进行比较。就这样，设备开发出来了 这项建议对显着改善POP手术修复的结果具有很高的潜力。