ENZYME-COATED URINARY PROSTHESES TO PREVENT ENCRUSTATION

涂有酶的泌尿假体可防止结垢

• 批准号: 6765199
• 负责人: Stephen Hollis Bartelmez
• 金额: $ 39.1万
• 依托单位: IXION BIOTECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6765199
• 关键词: antiinfective agents; biomaterial development /preparation; biomaterial evaluation; decarboxylases; elastomers; enzyme activity; molecular film; oxalates; photochemistry; surface coating; swine; urinary tract prosthesis

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.

描述（由申请人提供）：长期留置导尿管和支架在尿路中的使用往往受到限制，因为会发生结痂和生物膜的形成。迄今为止，尿路中使用的生物材料是完全生物相容性的，能够在没有尿路感染的情况下长时间承受尿路环境的影响。草酸钙是包覆材料的主要成分，由于尿液中的草酸盐浓度是草酸钙饱和和亚稳态尿过饱和的更重要参数，因此在放置支架和导尿管的尿液环境中减少草酸盐应该会减少甚至防止包覆。这一假设得到了我们I期可行性研究的支持，在该研究中，我们能够确定涂层“官能化”硅胶弹性体的条件。体外研究表明，与草酸脱羧酶共价连接的硅胶片与未涂覆的硅胶片相比，当放置在人工尿液中时，可抵抗草酸钙结痂和细菌粘附。我们建议继续开发酶包覆技术，以进一步提高固定化酶的稳定性和功能。这种包覆技术将用于开发酶包覆支架原型，以测试其在体内猪模型中防止结痂和细菌粘附的能力。因此，在第二阶段资助结束时，我们将完成抗结痂支架原型的临床前测试。将采取措施将这种酶涂层技术推向商业水平，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，扩大生产和临床测试。