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：
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
项目类别：
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

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

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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.

项目摘要骨盆器官脱垂（POP）是一种常见的，昂贵的状态 12.6％。在接受天然组织维修的人中，有40％的人将在2年之前失败，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，流行网眼是腹部疝网在510K申请中，这些产品已在POP维修申请下进行了营销，因此从未专门设计对于阴道。我们的研究表明，聚丙烯网植入会导致萎缩变性和阴道功能的丧失。聚丙烯的高材料刚度决定了网格由该聚合物制造的永久性变形 - 所有这些都导致网状负担增加，外国体内的反应增强以及结果不佳。我们假设从弹性体聚合物产生的网格与材料产生与阴道相同的数量级的刚度，一种有利于稳定孔的几何形状，与张力的皱纹最小的皱纹相比，宿主的响应比电流聚丙烯脱垂网眼。在这里，我们建议开发和评估网格由聚碳酸酯 - 尿烷（PCU）合成，一种弹性体，其固有刚度类似于阴道，但这也很难满足生理负荷需求。网眼设计辅助孔；意思是它们扩展而不是与加载合同。此外，网格可以打印3D，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述我们选择对PCU的僵硬对宿主对网格的反应的影响，因为此选择会影响实现与聚丙烯相当的结构支持和强度所需的材料量网。材料的量直接导致宿主响应的大小，但也可以避免或增强机械行为，例如在反馈到主机响应的设备中皱纹。因此，在将此设备推向最终在人类中使用，我们将研究我们的设计选择如何独立影响宿主对网格的材料和机制的反应：（目标1）植入小单位具有不同物质刚度，纤维宽度和阴道上的网状厚度的网格，而无需张紧和加载，（AIM 2）利用计算建模和离体测试来确定相同的影响关于全长网格的机械行为的设计选择，并带有加载。在AIM 3中，我们将研究如何选择将主机对材料的响应与网格力学产生的材料的响应之间的选择共同促进了对通过archocolopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopople，与常规聚丙烯网格相比，经过验证的动物模型。这样，设备开发了在此提案中，有很高的潜力可以显着改善流行手术修复的预后。