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: 9205246
• 负责人: STEVEN D ABRAMOWITCH
• 金额: $ 52.09万
• 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/9205246
• 关键词: Adopted; Affect; Anatomy; Area; 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; Mechanics; Modeling; Morphology; Notification; Operative Surgical Procedures; Organ; Orthopedics; Outcome; Pain; Patients; Physiological; Plants; Polypropylenes; Porosity; Primates; Property; Psychological reinforcement; Ptosis; Public Health; Quality of life; Risk; Solid; Stress; Surgeon; Surgical sutures; Testing; Thinness; Time; Tissues; United States; Vagina; Variant; Weight Gain; Woman; base; clinically translatable; 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; risk minimization; tissue degeneration

 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)：据估计，美国每年进行30万例手术来修复盆腔器官脱垂。高达40%的手术将在两年内失败，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状物。虽然目前的文献支持使用针织、轻质、宽孔的聚丙烯网眼，但理想的网眼尚未定义，而且到目前为止，没有一种网眼是没有并发症的。在灵长类阴囊固定术模型中，我们发现常用的脱垂网片对阴道的形态逻辑、结构和功能特性有负面影响，并与显著的异物反应有关。我们比较了植入原型脱垂网眼和新一代脱垂网眼后的反应(重量更小，孔径/孔隙率增加，硬度更低)，新材料的负面影响较小；然而，没有特定的网目特征可以预测宿主的反应。最关键的是，我们的研究显示，一旦施加机械张力，网眼植入前的特征通常不能反映出它所假定的情况。体外力学测试结合计算分析清楚地表明，脱垂网眼的几何形状可能明显不稳定，在施加少量张力的情况下会导致孔隙率的损失，并且网眼施加在阴道上的压力具有显着的地区性差异。这些效果在很大程度上是由网格的孔几何形状、张力程度和网格的锚定方式驱动的。在这里，我们假设两种不同的宿主反应与最常见的网眼并发症-疼痛和暴露-相关，以及网眼张紧引起的机械因素(毛孔塌陷和区域应力差异)推动宿主反应朝着一个方向或另一个方向。我们的目标是通过复杂的计算研究和对MESH的体外测试来指导我们的目标，这些研究表明，在非人类灵长类动物的固定模型中使用相同的MESH，我们可以在体内创建两个不同的机械环境，从而推动宿主对纤维化或退化的反应。在目标1中，我们通过植入孔朝向预定植入方向45度的聚丙烯网状物来测试毛孔塌陷导致纤维化的假说，以诱导毛孔塌陷。在目标2中，我们测试了这样的假设，即应力的区域变化(应力屏蔽)，通过沿着预期的植入方向植入网状物，并采用锚定策略来最大化保护阴道免受压力的面积，从而导致退行性反应。在目标3中，我们证实了我们在目标1和目标2中从女性切除的网眼中关于疼痛和网眼暴露的并发症的发现。为了进行额外的比较，我们使用了一组非人类灵长类动物，在其中植入网状物以创造一个既有毛孔塌陷又有应力屏蔽的环境，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在临床上得到翻译，并将有助于识别和开发用于脱垂手术的合成网片，将全球数百万女性网片并发症的风险降至最低。