Development of novel NO-releasing biomaterials for the prevention of biofilm-associated infections

随着时间的推移，由于新产品的出现以及加拿大人口的老龄化和日益衰弱，医疗器械的使用正在增加。医疗器械的主要问题是它们容易感染细菌或真菌病原体。当微生物附着在医疗器械上时，它们会生长成一种被称为生物膜的糖衣细胞群落，这种生物膜对抗生素或消毒剂的杀灭具有高度抵抗力。生物膜感染是常见的，难以用常规抗生素治疗，通常需要移除受感染的医疗器械。许多微生物也对我们有限的抗生素产生了抗药性，因此迫切需要新的方法来预防医疗器械感染。我们建议设计一种生物材料，将抵抗微生物定植，生物膜形成的第一个和必不可少的步骤。这种生物材料将涂有旨在排斥蛋白质（有助于微生物结合）和释放免疫调节化合物一氧化氮（NO）的化学物质。NO具有加速组织愈合和阻止细菌粘附于NO洗脱表面的优点。将测试这种生物材料在不使用抗生素的情况下阻止微生物结合同时改善愈合的能力。我们计划使用一系列生物物理、生物化学和微生物学技术测试其机械和生物学特性，最终在动物模型中测试材料的安全性，然后将其转化为人类使用。

The use of medical devices is increasing over time due to a combination of new products becoming available and an aging and increasingly debilitated Canadian population. The main problem with medical devices is their propensity to become infected with bacterial or fungal pathogens. When microorganisms become attached to a medical device, they grow into a sugar-coated community of cells called a biofilm, that becomes highly resistant to killing with either antibiotics or disinfectants. Biofilm infections are common and difficult to treat with conventional antibiotics, often requiring removal of an infected medical device. Many microorganisms are also becoming resistant to our limited arsenal of antibiotics, so new approaches to preventing infections of medical devices are urgently needed. We propose to design a biomaterial that will resist microbial colonization, the first and essential step of biofilm formation. This biomaterial will be coated with chemicals designed to repel proteins (which assist microorganisms in binding) and to release the immune modulatory compound nitric oxide (NO). NO has the advantages of both speeding healing of tissue and discouraging bacterial adherence to NO-eluting surfaces. This biomaterial will be tested for its ability to discourage microbial binding while improving healing, without using antibiotics. We plan to test its mechanical and biological properties using a range of biophysical, biochemical and microbiological techniques, ultimately testing the safety of the materials in an animal model prior to translation to human use.