Development and Commercialization of Nanostructured Resorbable Urogenital Grafts

摘要 膀胱癌是男性第四大常见癌症，女性第七大常见癌症 确诊后的预期寿命只有五年。晚期膀胱癌的修复需要切除 膀胱和使用自体肠道的新膀胱或尿管的构建。这些重建 有较高的慢性并发症和费用。并发症源于供者视力障碍、粘液分泌和 肠道组织对代谢物、药物和其他毒素的持续吸收。代谢失衡、结石 形成，严重腹泻是常见的，恶性肿瘤和穿孔也有报道。同种异体移植或 包埋材料不具有肠道组织的吸收性能，但被认为有不足 机械性能可能导致危及生命的穿孔。在第一阶段拨款的支持下 在NCI，该团队之前在成年小型猪身上开发和测试了一种再生膀胱移植物，实现了 膀胱组织再生和膀胱容量相当于使用自体肠段，并实现 支持体外实验的数据。为了建立在这些令人鼓舞的结果的基础上，该团队建议应用之前测试的 移植纳米技术在猪模型中产生可行和耐用的尿管，该模型也表现良好 作为一种由自体肠道组织构建的尿管，但这可能会减少 并发症、手术时间和费用。如果这一提议的项目成功，Nanovis领导的团队 基础设施和资金支持计划将纳米结构导尿管商业化。

Abstract 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 advanced bladder cancer requires removal of the bladder and construction of a neo bladder or urinary conduit using autologous bowel. These reconstructions have high chronic complications and cost. Complications stem from donor sight morbidity, mucus secretion and continued absorption of metabolites, drugs and other toxins by the bowel tissue. Metabolic imbalances, calculi formation, and severe diarrhea are common and malignancy and perforation are also reported. Allograft or xenograph materials do not have the absorptive properties of bowel tissue but are believed to have insufficient mechanical properties potentially leading to a life threatening perforation. With the support of a Phase I grant from the NCI, the team previously developed and tested a regenerative bladder graft in adult minipigs achieving bladder tissue regeneration and bladder capacity comparable to use of autologous bowel segments, and achieved supportive in vitro data. To build on these encouraging results the team proposes to apply the previously tested graft nanotechnology to generate a viable and durable urinary conduit in a porcine model that performs as well as a urinary conduit constructed from autologous bowel tissue but that has the potential for reduced complications, surgery time and expense. If this proposed program is successful, the team under Nanovis' infrastructure and financial support plans to commercialize the nanostructured urinary conduit.