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

基本信息

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
项目类别：
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

项目摘要

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（由适用提供）：估计每年在美国进行300,000次手术以修复骨盆器官脱垂。多达40％的人将失败2年，促使外科医生寻求材料来增强维修，最常见的是聚丙烯网。尽管当前的文献支持使用针织，轻巧，宽的孔聚丙烯网的使用，但尚未定义理想的网格，并且迄今为止没有网格没有并发症。在灵长类动物的sacro-colpopexy模型中，我们表明，常用的脱垂网眼对阴道的形态，结构和功能特性产生负面影响，并且与明显的外国身体反应有关。我们比较了植入原型脱垂网格后的响应与较新的产生脱垂网的响应（重量较低，孔径增加/孔隙率，较低的刚度），较新的材料的负面影响较小。但是，没有特定的网格特征可以预测宿主响应。最关键的是，我们的研究表明，一旦施加机械张力，网格的植入前特征通常不会反映其假设。离体机械测试与计算分析一起清楚地表明，脱垂网格可以显着不稳定的几何形状，导致孔隙率丧失，而较小的紧张局势却具有较小的张力，并且网状网格对阴道施加的压力具有显着的区域差异。这些效果在很大程度上是由网格的孔几何形状，张力程度以及网格锚定的方式驱动的。在这里，我们假设两个不同的宿主反应与最常见的网格并发症有关 - 疼痛和暴露，以及由网格张力（孔塌陷和区域应力差异）引起的机械因素将宿主响应推向一个方向或另一个方向。 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.在AIM 1中，我们检验了以下假设：孔塌陷通过将聚丙烯网植入带有孔的45度的聚丙烯网状网格到预期的植入方向以诱导孔隙塌陷而导致纤维化。在AIM 2中，我们检验了以下假设：应力（应力屏蔽）的区域变化通过沿预期的植入方向植入网格的锚固策略，从而导致退化反应，从而最大程度地避免了压力，从而最大程度地发挥了锚定策略。在AIM 3中，我们在AIMS 1和2中确认我们的发现在Mesh中的AIM 1和2中，女性的疼痛和网眼暴露并发症。为了进行其他比较，我们采用了一组非人类灵长类动物，其中植入了网格，以创建孔塌陷和应力屏蔽环境，以更好地模拟复杂的体内场景。我们预计，这项研究的发现将立即在临床上翻译，并有助于识别和开发合成网格的脱垂手术，以最大程度地减少全球数百万妇女的网格并发症的风险。