Novel Polymer Coatings to Prevent Biofilms on Urinary Stents and Catheters

描述（由申请人提供）：防止泌尿支架和导管上生物膜的新型聚合物涂层细菌感染和随后的泌尿支架和导管结壳是临床泌尿学中的一个持续问题，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个时间点发生感染，如果初始治疗持续时间未纠正基础疾病，则需要取出和重新植入。事实上，超过90%的长期留置导尿管的患者在一个月内会出现菌尿。考虑到每年插入约1亿个导尿管和泌尿支架，每年发生数百万个与器械相关的感染。已经开发了对泌尿装置的各种表面改性以防止细菌粘附，例如银涂层表面、控释抗生素和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，但都受到许多限制。显然，开发一种高效、持久的技术来预防泌尿支架和导尿管的细菌感染，将极大地有益于患者的健康和生活质量，并大大降低医疗保健成本。一种新的仿生策略，以产生排斥细胞和大分子的表面涂层，最近已经开发出来。这种策略的灵感来自于海洋贻贝分泌的独特蛋白质胶水，用于粘附到各种水下基质上。简而言之，已将多聚物偶联至氨基酸L-3，4-二羟基苯丙氨酸（DOPA），其为所谓的贻贝粘附蛋白（MAP）的关键组分。所得到的构建体具有大大减少的蛋白质吸附、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被认为负责将可固化聚合物锚定到基底上。在我们的I期可行性研究中进行的研究中，我们已经证明，DOPA模拟聚合物可以成功合成并应用于泌尿支架和导管材料表面，并且与无涂层对照相比，聚合物涂层表面显示出细菌粘附显著减少。该提案概述了从I期研究中选择的两种聚合物的合成、表征和评价。将以更大规模合成两种候选涂层聚合物，以提供足够的材料用于测试，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。长期而言，候选涂层的体外有效性将通过将涂层样品与细菌接种物长时间孵育来确定。将进行额外的实验，以确定这些涂层的生物相容性，并在试验动物模型中测试涂层泌尿支架和导管的有效性。 公共卫生相关性：泌尿支架和导尿管的细菌污染和结壳是泌尿外科中的一个持续性问题，并且经常导致尿路感染以及植入装置的取出和更换。旨在防止细菌粘附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医疗保健相关成本。

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.