ENZYME-COATED URINARY PROSTHESES TO PREVENT ENCRUSTATION

描述（申请人提供）：由于结壳和生物膜形成的发生，长期在尿路中留置导管和支架的使用通常受到限制。迄今为止，没有用于尿路的生物材料是完全生物相容的并且能够长时间承受泌尿环境的影响。在没有泌尿感染的情况下，草酸钙是结壳物质的主要成分由于尿中的草酸盐浓度是草酸钙饱和度和亚稳态尿过饱和度的更重要的参数，在放置支架和导管的泌尿环境中草酸盐的减少应该减少或甚至防止结壳。我们的I期可行性研究，其中我们能够确定用草酸盐降解酶草酸盐脱羧酶涂覆“官能化”硅氧烷弹性体（一种用于泌尿外科装置的常用生物材料）的条件。体外研究表明与草酸盐脱羧酶共价连接的硅氧烷盘抗草酸钙结壳和细菌粘附，与未涂覆的硅氧烷盘相反，当放入人造尿液中时在这个第二阶段的资助提案中，我们建议继续开发酶包被技术，以进一步提高固定化酶的稳定性和功能性。涂层支架将在体内猪模型中测试其防止结垢和细菌粘附的能力。因此，到第二阶段资助结束时，我们将完成抗结壳支架原型的临床前测试。届时，将采取措施，通过将其许可给支架和导管制造商，在FDA监管的设计控制下进行最终产品开发，扩大生产，和临床试验。

DESCRIPTION (provided by applicant): Use of indwelling catheters and stents long-term in the urinary tract is often limited due to the occurrence of encrustation and biofilm formation To date, there are no biomaterials used in the urinary tract that are completely biocompatible and capable of withstanding the effects of the urinary environment for extended time periods In the absence of urinary infection, calcium-oxalate is the principal component of the encrusted material Since oxalate concentrations of urine are the more important parameter for calcium-oxalate saturation and metastable urinary supersaturation, reduction of oxalate in the urinary environment in which stents and catheters are placed should reduce or even prevent encrustation This hypothesis is supported by our Phase I feasibility studies in which we were able to define conditions for coating "functionalized" silicone elastomer, a commonly used biomaterial for urological devices, with the oxalate-degrading enzyme, oxalate decarboxylase In vitro studies demonstrated that silicone discs covalently linked with oxalate decarboxylase were resistant to calcium-oxalate encrustation and bacterial adhesion, in contrast to uncoated silicone discs, when placed in artificial urine In this Phase II grant proposal, we propose to continue development of the enzyme-coating techniques to enhance further the stability and functionality of the immobilized enzyme This coating technology will then be used to develop a prototype enzyme-coated stent to be tested for its ability to prevent encrustation and bacterial adhesion in an in vivo pig model Thus, by the end of this Phase II grant, we will have completed the pre-clinical testing of a prototype encrustation-resistant stent At that time, measures will be taken to bring this enzyme-coating technology to the commercial level by licensing it to stent and catheter manufacturers for final product development under FDA regulated design control, scale-up production, and clinical testing.