Novel Polymer Coatings to Prevent Biofilms on Urinary Stents and Catheters

描述(申请人提供)：新型聚合物涂层用于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结痂是临床泌尿学中的一个长期问题，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个时候会受到感染，如果最初的治疗时间没有纠正潜在的情况，就需要回收和重新植入。事实上，90%以上使用长期导尿管的患者会在一个月内出现菌尿。考虑到每年大约有1亿个导尿管和尿路支架被植入，每年发生数百万与设备相关的感染。为了防止细菌粘连，已经开发了各种对尿路器械的表面改性，例如镀银表面、控释抗生素，以及改变疏水性的表面改性。这些方法都取得了不同程度的成功，但都受到了许多限制。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提高患者的福祉和生活质量，并大幅降低医疗保健成本。最近开发了一种新的仿生策略来生产排斥细胞和大分子的表面涂层。这一策略的灵感来自于海洋贻贝分泌的独特蛋白胶，用于粘着各种水下底物。简而言之，防污聚合物被偶联到氨基酸L-3，4-二羟基苯丙氨酸(DOPA)上，这是所谓的贻贝黏附蛋白(MAP)的关键成分。由此产生的构建物大大减少了蛋白质的吸附、哺乳动物细胞的附着以及微生物对金属和金属氧化物表面的附着。多巴被认为负责将防污聚合物锚定在基材上。在我们第一阶段可行性研究中进行的研究中，我们已经证明可以成功地合成DOPA模拟聚合物并将其应用于尿路支架和导管材料表面，并且与未涂层的对照相比，聚合物涂层表面的细菌粘附性显著降低。该提案概述了从第一阶段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进行更大规模的合成，以提供足够的材料进行测试，并确定可制造性。涂层的应用条件将进行调整，以优化其降低细菌粘附性的能力。从长远来看，候选涂层的体外效果将通过延长涂层样品与细菌接种剂的孵育时间来确定。还将进行其他实验，以确定这些涂层的生物相容性，并在实验动物模型中测试涂层尿路支架和导尿管的有效性。 公共卫生相关性：尿路支架和导尿管的细菌污染和结垢是泌尿外科的一个长期问题，经常导致尿路感染和植入物的回收和更换。旨在防止细菌附着的涂层将在很大程度上防止这一问题，提高患者的生活质量，并降低与医疗保健相关的成本。

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.