Bladder Tissue Engineering through Nanotechnology

通过纳米技术进行膀胱组织工程

• 批准号: 7140360
• 负责人: EARL Y CHENG
• 金额: $ 21.11万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140360
• 关键词: angiogenesis; biomaterial interface interaction; biotechnology; cell differentiation; cell proliferation; clinical research; fibroblast growth factor; human tissue; immunocytochemistry; laboratory rat; medical implant science; nanotechnology; protein binding; regeneration; smooth muscle; synthetic peptide; tissue /cell culture; tissue engineering; tissue support frame; urinary bladder; urinary bladder disorder; urinary bladder epithelium; urinary tract prosthesis; vascular endothelial growth factors

DESCRIPTION (provided by applicant): Patients with a neuropathic bladder have chronic medical problems with urinary incontinence, urinary infections, and potential renal failure. Conventional surgical management of the neuropathic bladder uses detubularized bowel as a patch (enterocystoplasty) to enlarge the bladder. However, this structural modification provides no functional improvement, and carries other complications. Alternative methods to enterocystoplasty have been explored through tissue engineering, by regrowing cells on biodegradable polymers or decellularized biological matrices. In all cases, some elements of regenerated bladder tissue structure have been obtained, but full bladder function has not been restored. Recent advances in nanotechnology provide a novel and alternative strategy for the use of tissue engineering scaffolds. Peptideamphiphile (PA) biomaterials have been developed, which self-assemble on the nanoscale to form fibrous gels, capable of retaining and releasing critical growth factors for regeneration. By non-covalently binding growth factors to the gel matrix, they are protected from degradation and can be released over time. The hypothesis of this proposal is that controlled delivery of bFGF and VEGF from a self-assembling nanofiber PA -scaffold composite will enhance the regeneration of bladder tissue. In this proposal, two well established complementary methods of binding growth factors to PAs will be characterized for their ability to effectively bind and release bFGF and VEGF (Aim 1). The in vitro effect of these PAs will then be assessed by seeding bladder cells within PA-scaffold composites and determining the effects on cell proliferation and differentiation (Aim 2). Lastly, the effects of the PAs on tissue regeneration will be studied in vivo by seeding bladder cells on PA-scaffold composites in a nude rat model. Differences in smooth muscle formation and angiogenesis in the regenerated tissue will be determined (Aim 3). This proposed research will provide the first evaluation of a novel tissue engineering nanotechnology for bladder regeneration.

描述(申请人提供)：神经性膀胱患者有慢性内科疾病，如尿失禁、尿路感染和潜在的肾功能衰竭。神经性膀胱的传统外科治疗使用拔管的肠道作为补片(肠膀胱成形术)来扩大膀胱。然而，这种结构修改没有提供功能改进，并带来了其他并发症。通过组织工程，通过在可生物降解的聚合物或脱细胞生物基质上再生细胞，已经探索了肠膀胱成形术的替代方法。在所有病例中，再生的膀胱组织结构的一些元素已经获得，但完整的膀胱功能尚未恢复。纳米技术的最新进展为组织工程支架的应用提供了一种新的替代策略。多肽两亲性(PA)生物材料已经被开发出来，它在纳米尺度上自组装形成纤维凝胶，能够保留和释放关键的生长因子以进行再生。通过非共价结合生长因子到凝胶基质，它们被保护不被降解，并可以随着时间的推移释放。这一设想的假设是，从自组装的纳米纤维PA-支架复合材料中控制地输送bFGF和VEGF将促进膀胱组织的再生。在这项提案中，两种公认的将生长因子与PAS结合的互补方法将以它们有效结合和释放bFGF和VEGF的能力为特征(目标1)。这些PA的体外效果将通过将膀胱细胞种植在PA-支架复合材料中并确定对细胞增殖和分化的影响来评估(目标2)。最后，通过将膀胱细胞种植在PA-支架复合材料上，在裸鼠模型上研究PAS对组织再生的影响。将确定再生组织中的平滑肌形成和血管生成的差异(目标3)。这项拟议的研究将首次对一种用于膀胱再生的新型组织工程纳米技术进行评估。