Bladder Tissue Engineering through Nanotechnology

描述（由申请人提供）：患有神经性膀胱的患者有尿失禁、尿路感染和潜在肾功能衰竭等慢性医学问题。神经性膀胱的常规外科治疗使用去管肠作为补片（肠囊成形术）来扩大膀胱。然而，这种结构上的修改并没有提供功能上的改善，而且还带来了其他的并发症。通过组织工程，通过在可生物降解聚合物或脱细胞生物基质上再生细胞，探索了肠囊成形术的替代方法。在所有病例中，已经获得了再生膀胱组织结构的一些元素，但膀胱功能尚未完全恢复。纳米技术的最新进展为组织工程支架的使用提供了一种新颖的替代策略。肽两亲性（PA）生物材料可以在纳米尺度上自组装形成纤维凝胶，能够保留和释放再生所需的关键生长因子。通过非共价结合生长因子与凝胶基质，它们可以免受降解并随时间释放。该提议的假设是，自组装的纳米纤维PA -支架复合材料控制bFGF和VEGF的递送将增强膀胱组织的再生。在本提案中，两种完善的互补生长因子与PAs结合的方法将以其有效结合和释放bFGF和VEGF的能力为特征（Aim 1）。这些PAs的体外效果将通过将膀胱细胞植入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（目的2）。最后，在裸鼠模型中，通过将膀胱细胞植入pa -支架复合材料，研究pa对组织再生的影响。将确定再生组织中平滑肌形成和血管生成的差异（目的3）。这项研究将首次评估一种用于膀胱再生的新型组织工程纳米技术。

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.