Comprehensive Evaluation of Prolapse Meshes by an Interdisciplinary Research Team

项目摘要/摘要： 跨学科研究团队对脱垂网片的综合评价 每年大约有20万美国妇女接受手术修复盆腔器官脱垂(6，7)。生物学和 合成网状物被广泛用于脱垂修复，以改善自然组织的解剖结果 目前故障率超过30%的维修。然而，到目前为止，几乎没有科学数据来指导 外科医生在选择特定的产品时。因此，将根据建议使用网格 因此，在试验和错误的基础上将其放置在妇女身上。越来越多的证据表明， 然而，与网片脱垂相关的并发症导致了不可接受的高发病率 包括感染、网眼收缩、网眼侵蚀、网眼暴露、盆腔、直肠和膀胱疼痛以及 性交困难。这种并发症已经变得足够严重，以至于FDA最近发布了警告 关于网眼的使用，特别是当它是经阴道放置时。因此，在这项建议中，我们的目标是建立一个 跨学科的科学家团队，致力于对以前或新上市的 脱垂网片和基于特定科学基础的下一代移植材料的开发 标准。在研究的第一阶段，我们确定了细胞内生化和结构的变化 脱垂的阴道影响被动和主动的机械行为，从而形成一种网状结构，在其中 缺陷被修复或补偿，使我们能够将脱垂的阴道恢复到 没有脱垂的状态。在第二阶段，我们假设当前脱垂的缺点是 网格的问题是它们太僵硬了。虽然这会导致修复具有更高的抗拉强度，但它发生在 组织功能受损，组织收缩加速，弹性和顺应性降低 平滑肌功能恶化。为了验证我们的假设，我们植入了常用的合成材料 应用黄金标准手术将脱垂植入非人灵长类动物的阴道 手术(腹部固定术)，然后确定细胞、生化和生物力学的影响 在植入后6个月的阴道上。最终，我们将通过阴道植入网状物 描述不同的宿主对这种手术方式的反应。在第三阶段，我们将探讨 未来脱垂手术移植物的发展。我们假设，由于它的生物诱导效应， 在修复阴道结构方面，生物/合成网片将优于单独使用合成网片 和功能。我们认为，脱垂修补术的一个关键但不发达的组成部分是重新- 建立平滑肌反应性，并因此测试临时生物活性支架的使用 在实现这一进程方面。通过这种方式，这项赠款提案提供了一种机制，以建立第一个团队 科学家致力于将脱垂网眼作为一种教育手段进行全面、公正的评估 目前和未来的脱垂外科医生，以及公众对与 某些材料。事实上，发展这样一个群体对于保护妇女的健康是必不可少的。

Project Summary/Abstract: Comprehensive Evaluation of Prolapse Meshes by an Interdisciplinary Research Team Each year roughly 200,000 U.S. women undergo a surgery to repair pelvic organ prolapse (6, 7). Biologic and synthetic meshes are widely used in prolapse repairs to improve anatomical outcomes over native tissue repairs which currently have a failure rate of over 30%. To date, however, there is little scientific data to guide surgeons in the selection of a particular product. As a result, meshes are used based on the recommendations of a local vendor and consequently, are placed in women on a trial and error basis. There is growing evidence, however, that the complications associated with prolapse meshes cause unacceptably high rates of morbidity including infection, mesh shrinkage, mesh erosion, mesh exposure, pelvic, rectal and bladder pain and dyspareunia. Such complications have become significant enough for the FDA to recently release a warning about mesh use, especially when it is placed transvaginally. In this proposal, we therefore, aim to establish an interdisciplinary team of scientists dedicated to the comprehensive testing of previously or newly marketed prolapse meshes and for the development of the next generation of graft materials based on specific scientific criteria. In the first phase of the study, we determine how biochemical and structural changes in the prolapsed vagina impact passive and active mechanical behavior so as to develop a mesh in which these deficiencies are repaired or compensated for, allowing us to restore the prolapsed vagina to the nonprolapsed condition. In the second phase, we hypothesize that the shortcoming of current prolapse meshes is that they are too stiff. While this results in a repair with increased tensile strength, it occurs at the expense of tissue function with accelerated tissue contraction, decreased elasticity and compliance, and deterioration of smooth muscle function. To test our hypothesis, we implant commonly used synthetic prolapse meshes into the vagina of nonhuman primates with prolapse using the gold standard surgical procedure (the abdominal sacrocolpopexy) and then define the cellular, biochemical and biomechanical impact on the vagina at 6 months post implantation. Eventually, we will implant meshes transvaginally to characterize the distinct host response to this surgical approach. In the third phase, we explore the development of future grafts for prolapse surgery. We hypothesize that because of its bioinductive effects, a combined biologic/synthetic mesh will be superior to a synthetic mesh alone in restoring vaginal structure and function. We propose that a key yet poorly developed component of prolapse repairs is the re- establishment of smooth muscle reactivity and therefore, test the use of a temporary biologically active scaffold in achieving this process. In this way, this grant proposal provides a mechanism to establish the first team of scientists dedicated to the comprehensive unbiased evaluation of prolapse meshes as a means of educating both current and future prolapse surgeons, and the public regarding potential problems associated with certain materials. Indeed, the development of such a group is imperative for protecting the health of women.