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）：在美国，估计每年进行300，000例手术以修复盆腔器官脱垂。高达40%的患者在2年内会失败，这促使外科医生寻求材料来加强修复，最常见的是聚丙烯补片。虽然当前文献支持使用编织、轻质、宽孔聚丙烯补片，但尚未定义理想补片，并且迄今为止没有一种补片不存在并发症。在灵长类动物阴道固定模型中，我们发现常用的脱垂补片对阴道的形态学、结构和功能特性具有负面影响，并与明显的异物反应相关。我们将原型脱垂补片植入后的反应与新一代脱垂补片（重量较轻、孔径/孔隙率增加、刚度较低）进行了比较，新材料的负面影响较小;然而，没有特定的补片特征可以预测宿主反应。最关键的是，我们的研究表明，补片的植入前特征通常不能反映其在施加机械张力后的假设。结合计算分析的离体力学试验清楚地表明，脱垂补片可能具有显著不稳定的几何形状，导致孔隙率损失，同时施加少量张力，并且补片施加在阴道上的应力具有显著的区域变异性。这些效应主要由补片的孔隙几何形状、张力程度以及补片的锚定方式驱动。在此，我们假设两种不同的宿主反应与最常见的补片并发症相关-疼痛和暴露，并且补片张紧导致的机械因素（孔隙塌陷和区域应力差异）驱动宿主反应朝向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补片的体外测试来指导，这些研究表明，在非人灵长类动物骶骨阴道固定术模型中使用相同的补片，我们可以创建两种不同的体内机械环境，这将驱动宿主对纤维化或变性的反应。在目标1中，我们通过植入聚丙烯补片（孔与预期植入方向成45度角）以诱导孔塌陷来检验孔塌陷导致纤维化的假设。在目标2中，我们检验了以下假设：应力的区域变化（应力屏蔽）通过沿着预期植入方向植入补片导致退行性反应，锚定策略可最大化屏蔽应力的阴道面积。在目标3中，我们证实了我们在目标1和目标2中关于女性患者因疼痛和补片暴露并发症而切除补片的发现。为了进行额外的比较，我们采用了一组非人类灵长类动物，其中植入了补片，以创建孔隙塌陷和应力屏蔽的环境，从而更好地模拟复杂的体内情况。我们预计，本研究的结果将立即用于临床，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的补片并发症风险。