Porosity and tensioning: Critical factors to consider when choosing a prolapse mesh

孔隙率和张力：选择脱垂网片时要考虑的关键因素

• 批准号: 9030077
• 负责人: STEVEN D ABRAMOWITCH
• 金额: $ 53.57万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-15 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9030077
• 关键词: Adopted; Affect; Area; Cations; Characteristics; Cicatrix; Clinical; Complex; Complication; Computer Analysis; Computer Simulation; Data; Development; Effectiveness; Environment; Experimental Models; Failure; Family; Fiber; Fibrosis; Foreign Bodies; Foundations; Future; Generations; Geometry; Goals; Hernia of abdominal cavity; Immune response; Implant; Knowledge; Life; Literature; Logic; Mechanics; Modeling; Notification; Operative Surgical Procedures; Organ; Orthopedics; Outcome; Pain; Patients; Physiological; Polypropylenes; Porosity; Primates; Property; Psychological reinforcement; Ptosis; Public Health; Quality of life; Risk; Solid; Stress; Surgeon; Surgical sutures; Testing; Time; Tissues; United States; Vagina; Variant; Weight Gain; Woman; base; computer studies; experience; falls; functional loss; implantation; improved; in vitro testing; in vivo; light weight; minimal risk; nonhuman primate; pelvic organ prolapse; preimplantation; propylene; prototype; public health relevance; repaired; response

 DESCRIPTION (provided by applicant): An estimated 300,000 surgeries are performed annually in the United States to repair pelvic organ prolapse. Up to 40% will fail by 2 years prompting surgeons to seek materials to augment repairs, most commonly poly- propylene mesh. While current literature supports the use of a knitted, lightweight, wide pore polypropylene mesh, the ideal mesh has not been defined, and no mesh to date is without complications. In a primate sacro- colpopexy model, we showed that commonly used prolapse meshes have a negative impact on the morpho- logic, structural, and functional properties of the vagina and are associated with a marked foreign body response. We compared the response following implantation of the prototype prolapse mesh to that of newer generation prolapse meshes (lower weight, increased pore size/porosity, lower stiffness), the newer materials had less of a negative effect; however, no particular mesh characteristic was predictive of the host response. Most critically, our studies revealed that a mesh's pre-implantation characteristics were generally not reflective of what it assumed once mechanical tension was applied. Ex vivo mechanical tests in conjunction with computational analyses clearly demonstrated that prolapse meshes can have markedly unstable geometries resulting in a loss of porosity with small applications of tension and that stresses imposed on the vagina by the mesh have significant regional variability. These effects are largely driven by the pore geometry of the mesh, the degree of tension, and how the mesh is anchored. Here we hypothesize that two distinct host responses are associated with the most common mesh complications - pain and exposure, and that mechanical factors resulting from mesh tensioning (pore collapse & regional stress differences) drive the host response towards one direction or the other. Our aims are guided by sophisticated computational studies and in-vitro testing of mesh which show that, using the same mesh in a non-human primate sacrocolpopexy model, we can create two distinct in-vivo mechanical environments that will drive the host-response towards fibrosis or degeneration. In Aim 1, we test the hypothesis that pore collapse results in fibrosis by implanting a polypropylene mesh with pores oriented 45 degrees to the intended implantation direction to induce pore collapse. In Aim 2, we test the hypothesis that regional variations in stress, (stress shielding), results in a degenerative response by implanting a mesh along the intended implantation direction with an anchoring strategy that maximizes the area of the vagina shielded from stress. In Aim 3, we confirm our findings in Aims 1 and 2 in mesh excised from women for the complications of pain and mesh exposure. For additional comparison, we employ a group of non-human primates in which mesh is implanted to create an environment of both pore collapse and stress shielding to better simulate the complex in-vivo scenario. We anticipate that the findings from this study will be immediately clinically translatable and will aid in the identificaion and development of synthetic meshes for prolapse surgeries that minimize risk of mesh complications for millions of women world-wide.

 描述（由申请人提供）：美国每年估计进行 300,000 例修复盆腔器官脱垂的手术。高达 40% 的修复会在 2 年后失效，这促使外科医生寻找材料来加强修复，最常见的是聚丙烯网。虽然当前文献支持使用针织、轻质、大孔聚丙烯网，但理想的网尚未定义，并且迄今为止没有任何网是没有并发症的。在灵长类骶骨阴道固定术模型中，我们表明常用的脱垂网片对阴道的形态、结构和功能特性有负面影响，并与明显的异物反应相关。我们将原型脱垂网植入后的反应与新一代脱垂网（重量更轻、孔径/孔隙率增加、刚度更低）进行了比较，较新的材料的负面影响较小；然而，没有特定的网格特征可以预测宿主的反应。最关键的是，我们的研究表明，网片的植入前特性通常不能反映其在施加机械张力后的假设情况。离体机械测试与计算分析相结合清楚地表明，脱垂网状物可能具有明显不稳定的几何形状，导致在施加较小的张力时孔隙率损失，并且网状物施加在阴道上的应力具有显着的区域变异性。这些效应很大程度上是由网格的孔隙几何形状、张力程度以及网格的锚定方式决定的。在这里，我们假设两种不同的宿主反应与最常见的网片并发症（疼痛和暴露）相关，并且网片张紧（孔隙塌陷和区域应力差异）引起的机械因素驱动宿主反应朝一个方向或另一个方向发展。我们的目标以复杂的计算研究和网格的体外测试为指导，这些研究表明，在非人类灵长类骶骨阴道固定术模型中使用相同的网格，我们可以创建两种不同的体内机械环境，从而驱动宿主对纤维化或退化的反应。在目标 1 中，我们通过植入与预期植入方向成 45 度的孔的聚丙烯网来诱导孔塌陷，从而测试孔塌陷导致纤维化的假设。在目标 2 中，我们测试了这样的假设：应力的区域变化（应力屏蔽）会导致退行性反应，方法是沿着预期的植入方向植入网片，并采用锚定策略最大化阴道免受应力的面积。在目标 3 中，我们确认了目标 1 和 2 中针对从女性身上切除的网片治疗疼痛和网片暴露并发症的发现。为了进行额外的比较，我们采用了一组非人类灵长类动物，其中植入了网状物，以创建孔隙塌陷和应力屏蔽的环境，以更好地模拟复杂的体内场景。我们预计这项研究的结果将立即应用于临床，并将有助于识别和开发用于脱垂手术的合成补片，从而最大限度地降低全球数百万女性补片并发症的风险。