Creation of the First Nanostructured Synthetic Regenerative Bladder Graft Materia

创建第一个纳米结构合成再生膀胱移植材料

基本信息

批准号：
7801310
负责人：
Chang Yao
金额：
$ 21.08万
依托单位：
NANOVIS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-22 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7801310
关键词：
Achievement Adsorption Animals Area Autologous Bladder Bladder Calculi Bladder Tissue Budgets Calcium Calculi Cell physiology Cell-Matrix Junction Cells Characteristics Chemicals Complex Cystectomy Development Diagnosis Diagnostic Neoplasm Staging Effectiveness Excision Family suidae Funding Future Genitourinary system Glycolic-Lactic Acid Polyester Goals Grant Growth Histocompatibility In Vitro Indiana Infection Inflammation Inflammatory Intestines Life Expectancy Malignant Neoplasms Malignant neoplasm of urinary bladder Marketing Mechanics Metabolic Modeling Morbidity - disease rate Mucous body substance Natural regeneration Nature Operative Surgical Procedures Patients Performance Phase Polymers Polyurethanes Preparation Procedures Property Proteins Research Resected Resistance Smooth Muscle Myocytes Solutions Staging Surface Surgeon Survival Rate System Technology Temperature Testing Tissue Engineering Tissues Transplantation Transplanted tissue Urothelial Cell Vision Woman Work base biodegradable polymer biomaterial compatibility cell type chemical property cost design implant material implantation improved in vitro Model in vivo men nanoscale nanostructured programs prototype public health relevance regenerative repaired scaffold success

项目摘要

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.

描述（由申请人提供）：膀胱癌是男性中的第四个最常见的癌症，也是诊断后仅五年的预期寿命的女性中第七大常见的癌症。修复该癌症的中期需要切除患病区域。然而，令人惊讶的是，尽管最近在其他组织的再生支架发展方面取得了进步，但在中期（T2）膀胱癌后（T2）膀胱癌的区域修复，包括膀胱后的膀胱修复。出于任何原因，最常用的选择需要切除和更换部分膀胱的患者是用肠道的一部分替换切除区域。切除的组织会给患者带来严重的并发症，因为它将粘液分泌到膀胱中，导致石材形成并可能导致癌症。正在开发的期权包括种子脚手架，这些脚手架很可能为替代大部分膀胱的解决方案提供解决方案，但潜在的程序复杂性和费用可能会限制其对部分/区域维修的适用性。细胞矩阵在介绍市场时提供了希望，但此后因缺乏长期机械强度而受到批评。由于这些原因，该项目的目标是开发第一个合成纳米结构的再生膀胱移植物材料。纳米结构的材料已成为组织工程研究的关键领域，因为它们能够模仿粗糙度并因此是天然组织的表面能量。先前的工作证明了一种纳米表面控制的机制，可调节蛋白质吸附驱动的细胞附着和生长，并出乎意料地是膀胱修复移植物材料，可减少膀胱石的形成。拟议的产品将利用这些发现来创建简单而优雅的产品解决方案。本提案将通过重点关注纳米结构的多层生物降解聚合物矩阵来实现这一目标。 Nanovis将准备这些移植原型，并在体外评估其再生特性，并表征其机械和生物相容性的特性。通过这种方式，该提案的具体目的将：（i）从聚氨酯（PU）和聚乳乙酰基 - 果糖 - 甘露葡萄糖（PLGA）（75:25wt。％PU：PLGA）中准备分层和分级的多孔纳米结构可生物降解矩阵纳米级PU和PLGA上钙石或细菌定植的可能性，（iii）在预算限制内对最佳纳米结构膀胱结构进行了初步的体内评估。公共卫生相关性：膀胱和尿液系统的手术修复是一个常见的程序，但令人惊讶的是，没有合成的再生移植物材料。 Nanovis的提议旨在开发一种合成的纳米结构膀胱移植物材料，该材料具有抗膀胱结石形成能力，可帮助每年有50,000多名美国患者，需要这种程序。