Novel Polymer Coatings to Prevent Biofilms on Urinary Stents and Catheters

描述（由申请人提供）：新型聚合物涂层防止尿路支架和导尿管上的生物膜细菌感染和随后的尿路支架和导尿管的结壳是临床泌尿外科的一个持续问题，并导致显著的患者发病率和死亡率。大多数植入的支架在某些时候会感染，如果最初的治疗时间不能纠正潜在的状况，则需要取出并重新植入。事实上，超过90%的长期导尿管患者在一个月内会出现细菌尿。考虑到每年约有1亿个导尿管和尿道支架被插入，每年发生数百万例与器械相关的感染。为了防止细菌的粘附，人们开发了各种各样的表面修饰，如镀银表面、控释抗生素和表面修饰以改变疏水性。这些方法取得了不同程度的成功，但都有许多局限性。显然，开发一种高效、持久的技术来预防尿路支架和导尿管的细菌感染，将极大地有利于患者的健康和生活质量，并大大降低医疗成本。最近发展了一种新的仿生策略来产生排斥细胞和大分子的表面涂层。这种策略的灵感来自于海洋贻贝分泌的独特的蛋白胶，这种蛋白胶可以粘附在各种水下基质上。简而言之，防污聚合物已与氨基酸l -3,4-二羟基苯丙氨酸（DOPA）偶联，这是所谓的贻贝粘附蛋白（MAPs）的关键成分。由此产生的结构大大减少了蛋白质吸附、哺乳动物细胞附着和微生物对金属和金属氧化物表面的附着。DOPA被认为是负责将防污聚合物锚定在底物上。在我们一期可行性研究的研究中，我们已经证明dopa模拟聚合物可以成功合成并应用于尿路支架和导管材料表面，并且与未涂覆的对照相比，聚合物涂覆的表面显示出细菌粘附性的显著降低。本提案概述了从I期研究中选择的两种聚合物的合成，表征和评价。这两种候选涂层聚合物将以更大的规模合成，为测试提供足够的材料，并确定可制造性。将调整涂层的应用条件，以优化其减少细菌粘附的能力。长期来看，候选涂层的体外功效将通过将涂层样品与细菌接种物长时间孵育来确定。将进行更多的实验来确定这些涂层的生物相容性，并在中试动物模型中测试涂层尿路支架和导尿管的功效。

DESCRIPTION (provided by applicant): Novel Polymer Coatings to Prevent Biofilms on Urinary Stents and Catheters Bacterial infection and subsequent encrustation of urinary stents and catheters is a persistent problem in clinical urology and leads to significant patient morbidity and mortality. Most implanted stents become infected at some point, requiring retrieval and re-implantation if the initial treatment duration did not correct the underlying condition. Indeed, more than 90% of patients who have a long-term catheter develop bacteriuria within a month. Considering that about 100 million urethral catheters and urinary stents are inserted each year, millions of device-associated infections occur annually. Various surface modifications to urinary devices have been developed to prevent bacterial adhesion, such as silver-coated surfaces, control-release antibiotics, and surface modification to change hydrophobicity. These approaches have enjoyed varying degrees of success, but all suffer from numerous limitations. Clearly, development of a highly efficacious, long-lasting technology for preventing bacterial infections of urinary stents and catheters would dramatically benefit patients' well-being and quality of life and substantially reduce health care costs. A novel biomimetic strategy to produce surface coatings that repel cells and macromolecules has recently been developed. This strategy was inspired by the unique protein glues that marine mussels secrete for adhesion to various underwater substrates. In brief, antifouling polymers have been coupled to the amino acid L-3,4-dihydroxyphenylalanine (DOPA), a key component of so-called mussel adhesive proteins (MAPs). The resulting constructs have greatly reduced protein adsorption, mammalian cell attachment, and microbial attachment to metal and metal oxide surfaces. DOPA is believed to be responsible for anchoring the antifouling polymer to the substrates. In the research conducted in our Phase I feasibility study, we have demonstrated that DOPA-mimic polymers can be successfully synthesized and applied to urinary stent and catheter material surfaces and that the polymer-coated surfaces exhibited a significant reduction in bacterial adhesion compared to uncoated controls. This proposal outlines the synthesis, characterization, and evaluation of two polymers selected from the Phase I study. The two candidate coating polymers will be synthesized in a larger scale to provide sufficient material for the testing, and to determine manufacturability. Application conditions for the coatings will be adjusted to optimize their ability to reduce bacterial adhesion. Long-term, the in vitro efficacy of the candidate coatings will be determined by incubating coated samples with bacterial inoculums for extended periods. Additional experiments will be performed to determine the biocompatibility of these coatings and to test the efficacy of coated urinary stents and catheters in pilot animal models. PUBLIC HEALTH RELEVANCE: Bacterial contamination and encrustation of urinary stents and catheters is a persistent problem in urology, and often leads to urinary tract infection and retrieval and replacement of the implanted devices. Coatings that are designed to prevent bacterial adherent will largely prevent this problem, improving the quality of life for patients and reducing healthcare-related costs.