Creation of the First Nanostructured Synthetic Regenerative Bladder Graft Materia

描述（由申请人提供）：膀胱癌是男性第四大常见癌症，女性第七大常见癌症，诊断后预期寿命仅为5年。这种癌症的中期修复需要切除病变区域。然而，令人惊讶的是，尽管最近在其他组织再生支架的发展方面取得了进展，但泌尿生殖系统的局部修复，特别是包括中期（T2）膀胱癌后膀胱的修复，手术选择却少得惊人。对于出于任何原因需要切除和更换部分膀胱的患者，最常用的选择是用一段肠来替换切除的部分。切除的组织可能会给患者带来严重的并发症，因为它会向膀胱分泌粘液，导致结石形成，并可能导致癌症。正在开发的选择包括种子支架，它可能为膀胱的大部分替换提供解决方案，但潜在的程序复杂性和费用可能限制其部分/局部修复的适用性。无细胞基质在引入市场时提供了希望，但由于缺乏长期机械强度而受到批评。基于这些原因，该项目的目标是开发第一个合成纳米结构再生膀胱移植材料。纳米结构材料由于能够模拟自然组织的粗糙度和表面能，已经成为组织工程研究的一个关键领域。先前的研究已经证明了一种纳米表面控制机制，可以调节蛋白质吸附驱动的细胞附着和生长，以及一种膀胱修复移植材料，可以减少膀胱结石的形成。建议的产品将利用这些发现来创建一个简单而优雅的产品解决方案。目前的提案将通过专注于纳米结构多层生物可降解聚合物基质的使用来实现这一目标。Nanovis将制备这些移植物原型，并评估其体外再生性能，表征其机械和生物相容性。这样，建议的具体目标将：(i)用聚氨酯（PU）和聚乳酸-羟基乙酸酯（PLGA） （75:25 wt.% PU:PLGA）支架制备层状和分级多孔纳米结构可生物降解基质，并表征其机械和化学性能；（ii）使用体外模型评估尿路上皮和平滑肌细胞功能，以及钙石或细菌在纳米级PU和PLGA上定植的可能性。（iii）在预算限制范围内对最佳纳米结构膀胱结构进行初步体内评估。

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.