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

基本信息

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
项目类别：
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&apos 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

项目摘要

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）：每年约有200,000名美国妇女接受修复骨盆器官脱垂的手术（6，7）。生物学和合成网格广泛用于脱垂维修中，以改善本地组织维修的解剖结局，而本地组织维修的失效率超过30％。但是，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。结果，基于本地供应商的建议使用网格，因此在妇女的试用和错误基础上使用网格。然而，越来越多的证据表明，与脱垂网格相关的并发症会导致发病率不高，包括感染，网状收缩，网状侵蚀，网状侵蚀，网状暴露，骨盆，直肠和膀胱疼痛以及肿瘤疾病。此类并发症已经变得足够重要，可以使FDA最近发布有关网格使用的警告，尤其是在经染色时。因此，在该提案中，我们旨在建立一个跨学科的科学家团队，致力于对以前或新销售的脱垂网眼进行全面测试，并根据特定的科学标准开发下一代移植物材料。在研究的第一阶段，我们确定阴道脱垂的生化和结构变化如何影响被动和主动的机械行为，从而开发出修复或补偿这些缺陷的网格，从而使我们能够将阴道的阴道恢复为非验证条件。在第二阶段，我们假设当前脱垂网眼的缺点是它们太硬了。尽管这会导致拉伸强度增加的修复，但它以组织功能为代价以加速组织收缩，弹性和依从性降低以及平滑肌功能的恶化而发生。 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. 最终，我们将经植入式网格，以表征对这种手术方法的独特宿主反应。在第三阶段，我们探讨了未来移植物进行脱垂手术的发展。我们假设，由于其生物倾向效应，在恢复阴道结构和功能中，合并的生物/合成网格组合将优于合成网格。我们建议，脱垂维修的关键却不佳的成分是重新建立平滑肌反应性，因此测试在实现这一过程中使用临时具有生物活性的脚手架的使用。通过这种方式，该赠款提案提供了一种机制，可以建立一支专门针对对脱垂网眼的全面评估的科学家，作为对当前和未来的脱垂外科医生进行教育的一种手段，以及公众就某些材料相关的潜在问题进行教育。确实，这种群体的发展对于保护妇女的健康至关重要。公共卫生相关性：骨盆器官的脱垂（即异常下降）是一种常见的昂贵条件，会对全球数百万妇女的生活产生负面影响。生物学和合成网通常用于对天然组织维修的解剖结局改善引起的脱垂的手术修复。但是，几乎没有科学数据，可以选择特定产品的选择。不幸的是，与某些网格相关的并发症会导致高度高的发病率，包括感染，组织收缩，阴道排出和疼痛。在此提案中，我们旨在建立一个全面的网格测试中心，在该中心中，可以客观地测试以前或新销售的脱垂网眼，并且可以根据特定的科学标准开发下一代脱垂网眼。