Creation of the First Nanostructured Synthetic Regenerative Bladder Graft Materia

DESCRIPTION (provided by applicant): Bladder cancer is the fourth most common cancer among men and the seventh most common cancer in women with a life expectancy of only five years after diagnosis. Repair of the mid stage of this cancer requires excision of the diseased area. Surprisingly however, regional repair of the genitourinary system and specifically including the repair of the bladder after mid stage (T2) bladder cancer has surprisingly few surgical options despite the recent advances in the development of regenerative scaffolds for other tissues. The most commonly used option for patients requiring resection and replacement of part of their bladder for any reason is the replacement of the resected area with a section of the intestine. The resected tissue can cause serious complications for the patient because it secretes mucus into the bladder, causing stone formation and potentially cancer. Options under development include seeded scaffolds which are likely to offer a solution for replacement of large portions of the bladder but potential procedural complexity and expense may limit their suitability for partial/regional repairs. Acellular matrices offered promise upon introduction to the market but have since been criticized for a lack of long term mechanical strength. For these reasons, the goal of this project is to develop the first synthetic nanostructured regenerative bladder graft material. Nanostructured materials have become a key area of tissue engineering research due to their ability to mimic the roughness and, consequently, the surface energy of natural tissues. Prior work has demonstrated a nanosurface controlled mechanism of moderating protein adsorption driven cell attachment and growth and unexpectedly a bladder repair graft material that reduces bladder stone formation. The proposed product will leverage these findings to create a simple and elegant product solution. The present proposal will reach this goal by focusing on the use of nanostructured multilayered biodegradable polymer matrices. Nanovis will prepare these graft prototypes and evaluate their regenerative properties in vitro and characterize their mechanical and biocompatibility properties. In this manner the specific aims of the proposal will : (i) prepare layered and graded porous nanostructured biodegradable matrices from polyurethane (PU) and poly-lactide-co-glycolide (PLGA) (75:25 wt.% PU:PLGA) scaffolds and characterize its mechanical and chemical properties, (ii) use in vitro models to assess the urothelial and smooth muscle cell functions and the likelihood of calcium stone or bacterial colonization on nanoscale PU and PLGA, and (iii) conduct a preliminary in vivo assessment of the best nanostructured bladder constructs within the budget limitations. PUBLIC HEALTH RELEVANCE: Surgical repair of the bladder and urogential system is a common procedure yet surprisingly a synthetic regenerative graft material is not available. Nanovis' proposal seeks to develop a synthetic nanostructured bladder graft material that is resistant to bladder stone formation suitable to help the over 50,000 U.S. patients per year in need of such a procedure.