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: 8305152
• 负责人: Pamela A. Moalli
• 金额: $ 45.87万
• 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/8305152
• 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; 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; abstracting; base; experience; falls; graduate student; implantation; improved; in vivo; mechanical behavior; multidisciplinary; nerve supply; next generation; nonhuman primate; rectal; regenerative; repaired; response; scaffold; soft tissue; success; tissue regeneration; tissue repair

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.

项目概要/摘要： 跨学科研究小组对脱垂补片的综合评价 每年大约有200，000名美国女性接受手术来修复盆腔器官脱垂（6，7）。 生物和 合成补片广泛用于脱垂修复，以改善与天然组织相比的解剖学结果 目前故障率超过30%的维修。 然而，迄今为止，几乎没有科学数据可以指导 外科医生选择特定产品。 因此，根据建议使用网格 因此，在试验和错误的基础上，将其安置在妇女身上。越来越多的证据表明， 然而，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， 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 关于补片的使用，特别是当它被放置在阴道。 因此，我们在这项建议中， 一个跨学科的科学家团队，致力于全面测试以前或新上市的 脱垂补片和基于特定科学的下一代移植材料的开发 的搜索. 在第一阶段的研究中，我们确定了生物化学和结构的变化， 脱垂的阴道影响被动和主动的机械行为， 缺陷得到修复或补偿，使我们能够将脱垂的阴道恢复到 非脱垂状态。 在第二阶段，我们假设目前脱垂的缺点 他们的缺点是太硬了。 虽然这导致了具有增加的拉伸强度的修复，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，以及 平滑肌功能恶化。 为了验证我们的假设，我们植入常用的合成物质 使用黄金标准外科手术将脱垂网片插入患有脱垂的非人类灵长类动物的阴道 程序（腹部骶骨阴道固定术），然后定义细胞，生物化学和生物力学的影响 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， 描述宿主对这种手术方法的独特反应。 在第三阶段，我们探索 用于脱垂手术的未来移植物的开发。我们假设，由于其生物诱导效应， 在恢复阴道结构方面，组合的生物/合成补片将优于单独的合成补片上级 和功能 我们认为，脱垂修复的一个关键但发展不足的组成部分是重新- 建立平滑肌反应性，并因此测试临时生物活性支架的使用 在实现这一过程中。 通过这种方式，这项赠款提案提供了一个机制，以建立第一个团队， 科学家致力于对脱垂补片进行全面、公正的评价， 目前和未来的脱垂外科医生，以及公众对潜在的问题， 某些材料。 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。