Comprehensive Evaluation of Prolapse Meshes by an Interdisciplinary Research Team

跨学科研究团队对脱垂网片的综合评估

• 批准号: 7727511
• 负责人: Pamela A. Moalli
• 金额: $ 39.44万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7727511
• 关键词: Abdomen; Abdominal Surgical Procedures; Acute; Address; Adrenergic Antagonists; Adult; Age; Agonist; Anatomy; Applications Grants; Autologous; Behavior; Biochemical; Biocompatible Materials; Biological; Biological Assay; Biomechanics; Biomedical Engineering; Bladder; Chronic; Clinical; Clinical Data; Collagen; Connective Tissue; Data; Deterioration; Development; Dyspareunia; Elasticity; Elastin; Estrogens; Evaluation; Extracellular Matrix; Failure; Foundations; Funding Mechanisms; Future; Goals; Gold; Grant; Health; Human; Hysterectomy; Immune response; Implant; Incidence; Infection; Inferior; Institutes; Institution; Integration Host Factors; Interdisciplinary Study; Lead; Length; Life; Maintenance; Marketing; Mechanics; Mentors; Methods; Modeling; Morbidity - disease rate; Muscarinics; Muscle function; Occupations; Operative Surgical Procedures; Organ; Outcome; Pain; Patients; Pelvis; Phase; Physiological; Plague; Polypropylenes; Procedures; Process; Progesterone; Property; Protocols documentation; Ptosis; Public Health; Recommendation; Relative (related person); Reproductive Physiology; Scientist; Sheep; Smooth Muscle; Structure; Surgeon; Surgical incisions; Techniques; Tensile Strength; Testing; Textiles; Tissues; Transplanted tissue; Vagina; Vaginal Discharge; Vaginal Prolapses; Vaginal delivery procedure; Vendor; Woman; Women' s Health; Wound Healing; base; experience; falls; graduate student; implantation; improved; in vivo; mechanical behavior; multidisciplinary; nerve supply; next generation; nonhuman primate; public health relevance; rectal; regenerative; repaired; response; scaffold; soft tissue; success; tissue regeneration

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Prolapse (i.e., abnormal descent) of the pelvic organs is a common costly condition that negatively impacts the lives of millions of women world-wide. Biologic and synthetic meshes are often used in the surgical repair of prolapse due to improved anatomical outcomes over native tissue repairs; but with little scientific data on which to base the selection of a particular product. Unfortunately, the complications associated with certain meshes cause unacceptably high rates of morbidity including infection, tissue contraction, vaginal discharge, and pain. In this proposal, we aim to establish a comprehensive mesh testing center in which previously or newly marketed prolapse meshes can be objectively tested and the next generation of prolapse meshes can be developed based on specific scientific criteria.

描述（由申请人提供）：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）。 生物和合成补片广泛用于脱垂修复，以改善与自体组织修复相比的解剖结局，目前自体组织修复的失败率超过30%。 然而，到目前为止，几乎没有科学数据来指导外科医生选择特定的产品。 因此，根据当地供应商的建议使用补片，并在试错的基础上将其植入妇女体内。然而，越来越多的证据表明，与脱垂补片相关的并发症导致不可接受的高发病率，包括感染、补片收缩、补片侵蚀、补片暴露、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最近发布了关于补片使用的警告，特别是当它被放置在阴道内时。 因此，在本提案中，我们的目标是建立一支跨学科的科学家团队，致力于对之前或新上市的脱垂网片进行全面测试，并根据特定的科学标准开发下一代移植材料。 在研究的第一阶段，我们确定脱垂阴道的生物化学和结构变化如何影响被动和主动力学行为，以便开发一种修复或补偿这些缺陷的网状物，使我们能够将脱垂阴道恢复到非脱垂状态。 在第二阶段，我们假设目前脱垂补片的缺点是它们太硬。 虽然这导致了具有增加的拉伸强度的修复，但其发生是以组织功能为代价的，具有加速的组织收缩、降低的弹性和顺应性以及平滑肌功能的恶化。 为了验证我们的假设，我们使用金标准手术程序（腹部骶骨阴道固定术）将常用的合成脱垂补片植入脱垂的非人灵长类动物的阴道中，然后在植入后6个月确定对阴道的细胞、生物化学和生物力学影响。 最终，我们将经阴道植入补片，以表征这种手术方法的不同宿主反应。 在第三阶段，我们探讨了未来脱垂手术移植物的发展。我们假设，由于其生物诱导效应，联合生物/合成补片在恢复阴道结构和功能方面上级单独的合成补片。 我们提出，脱垂修复的一个关键但发展不足的组成部分是重建平滑肌反应性，因此，测试使用临时生物活性支架实现这一过程。 通过这种方式，该拨款提案提供了一种机制，以建立第一个致力于脱垂补片全面公正评价的科学家团队，作为教育当前和未来脱垂外科医生以及公众与某些材料相关的潜在问题的一种手段。 事实上，发展这样一个小组对于保护妇女健康是必不可少的。 公共卫生相关性：脱垂（即，骨盆器官的异常下降）是一种常见的昂贵的病症，其对全世界数百万妇女的生活产生负面影响。 生物补片和合成补片通常用于脱垂的手术修复，因为其解剖结局优于自体组织修复;但选择特定产品时几乎没有科学数据。 不幸的是，与某些补片相关的并发症导致不可接受的高发病率，包括感染、组织收缩、阴道分泌物和疼痛。 在该提案中，我们的目标是建立一个综合性补片测试中心，在该中心可以客观地测试之前或新上市的脱垂补片，并可以根据特定的科学标准开发下一代脱垂补片。