Core-Shell Fiber Mesh for the Treatment of UI and PFD in Elderly Women

描述(由申请人提供)：这项第一阶段的SBIR申请调查了使用由新型定时释放纤维组成的外科网片可控地收缩和支持盆腔器官的可行性，长期目标是纠正老年妇女的盆底疾病(PFD)。包括尿失禁(UI)在内的PFD影响着三分之一的美国女性；如果不进行治疗，它们是老年人骨折的主要触发因素，也是疗养院入院的主要原因(50%)。用于治疗产后功能障碍的外科工具包的市场价格约为每年10亿美元，随着婴儿潮一代的年龄增长，市场规模还在不断增长。最先进的治疗方法使用合成网状物或胶原基质来增强自然盆腔组织，增强对生殖器脱垂患者尿路或生殖器的尿路膀胱连接处(UVJ，即膀胱颈)的支持。然而，在拉伸商业可用的外科网片方面存在困难，这是拨入最佳支撑水平的障碍。过度紧张会导致尿路狭窄、排尿功能障碍和组织侵蚀。为了克服这一障碍，Novo Conour提出了可生物降解的核壳纤维，以逐渐和可调地收缩患者的筋膜，提供精细的支撑水平。核芯将被贝壳预拉紧并固定，这样在其生物降解时，网状支架将收缩并抬起邻近的组织。纤维的核心和外壳分别由聚(庚二酸甘油)(PGS)和聚(1，3-二(羧基苯氧基)丙烷)(PCPP)组成，分别用于数周可调的表面腐蚀。具体目标是：(1)通过制备第一批可生物降解、定时释放和预张紧的纤维来论证其可行性。植入前的净纤维长度将作为芯体直径、初始应变、拉伸模数和壳体直径的函数来确定。纤维提供的升力将被确定为体外降解率、芯子直径、芯子拉伸模数、初始应变和施加重量以模拟组织质量的函数。(2)评价核壳纤维的体内降解和收缩速率与其尺寸的关系。将纤维植入新西兰大白兔体内，每隔4个月采集一次。网眼必须保持器官重量至少2-3个月。Novo Conour的SBIR计划展示了这些新型可生物降解的定时释放核壳纤维的关键属性，这些纤维将作为网状物集成在盆底微创手术的支撑包中，从而提高手术的安全性和有效性。它们的发展将改变临床实践，消除外科医生最初过度紧张网片的动机，减少对患者的副作用(例如排尿功能障碍和组织侵蚀)。这项拟议的研究利用了连续创业家和执业妇科医生Novo Conour总裁PI和具有聚合物制造和表征经验的化学工程、制药和药物化学教授皮斯博士之间的长期合作。Novo Conour的长期目标是开发新的外科技术来治疗PFDs，改善老年妇女的生活质量。 公共卫生相关性：盆底疾病(PFD)，包括尿失禁和盆腔器官脱垂，对数百万女性造成不利影响，导致尴尬、丧失工作能力和入住疗养院。用于外科治疗PFDs的最先进的外科网片突然施加张力，诱使外科医生过度收紧，并增加患者的手术并发症(例如组织侵蚀和排尿功能障碍)。Novo Conour将制造和评估创新的预张紧可生物降解核壳纤维，旨在逐步和可调地施加网眼张力，以改善数百万老年妇女的手术结果。

DESCRIPTION (provided by applicant): This phase I SBIR application investigates the feasibility of using surgical mesh composed of novel timed-release fibers to controllably contract and provide support to pelvic organs with the long term goal of correcting pelvic floor disorders (PFDs) in elderly women. PFDs including urinary incontinence (UI) affect one in three US women; left untreated they are a major trigger of fractures in the elderly and a primary cause (>50%) of nursing home admissions. The market for surgical kits to treat PFDs is ~$1B/yr and growing as baby boomers age. State-of-the-art treatment uses synthetic mesh or collagen matrixes to augment natural pelvic tissue, enhancing support to the urethrovesicle junction (UVJ, i.e. bladder neck) in UI or genital organs in genital prolapse. However, difficulty in tensioning commercially available surgical mesh presents a barrier to dialing in optimal levels of support. Over-tensioning leads to urethral stenosis, voiding dysfunction, and tissue erosion. To overcome this barrier, Novo Contour proposes biodegradable core-shell fibers to gradually and tunably contract the patient's fascia, providing refined levels of support. The core will be pre-tensioned and secured by the shell so that upon its biodegradation, the mesh scaffold will shrink and lift adjacent tissue. The fiber core and shell are composed of poly(glycerol sebacate) (PGS) and poly(1,3-Bis- (carboxyphenoxy)propane) (PCPP), respectively selected to tunably surface erode over several weeks. The Specific Aims are: (1) To demonstrate feasibility by preparing the first biodegradable, timed-release, and pre- tensioned fibers. The net pre-implant fiber length will be determined as a function of the core's diameter, initial strain, and tensile modulus and shell's diameter. Lift provided by the fibers will be determined as a function of in vitro degradation rate, core diameter, core tensile modulus, initial strain, and applied weight to simulate tissue mass. (2) To evaluate in vivo degradation and contraction rates of core-shell fibers as a function of their dimensions. Fibers will be implanted in New Zealand white rabbits and harvested at intervals out to 4 months. The mesh must sustain organ weight for at least 2-3 months. Novo Contour's SBIR program demonstrates key attributes of these novel biodegradable timed-release core-shell fibers to be integrated as mesh in support kits for minimally invasive pelvic floor surgery, improving surgical safety and efficacy. Their development will change clinical practice by removing the motive for surgeons to initially over tension mesh, decreasing side effects for the patient (e.g. voiding dysfunction & tissue erosion). The proposed research takes advantage of a standing collaboration between the PI, President of Novo Contour, a serial entrepreneur & practicing gynecologist, and Dr. Pease, a Professor of Chemical Engineering and Pharmaceutics & Pharmaceutical Chemistry with experience in polymer fabrication and characterization. The long term objective of Novo Contour is to develop novel surgical techniques to treat PFDs, improving the quality of life for elderly women. PUBLIC HEALTH RELEVANCE: Pelvic floor disorders (PFDs) including urinary incontinence and pelvic organ prolapse adversely affect millions of women leading to embarrassment, incapacitating falls, and nursing home admission. State-of-the- art surgical mesh to surgically treat PFDs abruptly applies tension, tempting the surgeon to over tighten it and increasing surgical complications for patients (e.g. tissue erosion & voiding dysfunction). Novo Contour will fabricate and evaluate innovative pre-tensioned biodegradable core-shell fibers designed to gradually and tunably apply mesh tension to improve surgical outcomes for millions of elderly women.