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

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 (gt50%) of nursing home admissions. The marketfor 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) inUI 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. TheSpecific 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 modulusand 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 and tissue erosion). The proposed research takes advantage of a standing collaboration between the PI, President ofNovo Contour, a serial entrepreneur and practicing gynecologist, and Dr. Pease, a Professor of Chemical Engineering and Pharmaceutics and Pharmaceutical Chemistry with experience in polymer fabrication and characterization. The long term objective of NovoContour 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 millionsof 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 and 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.