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

随着时间的推移，医疗设备的使用正在增加，这是由于新产品的推出，以及加拿大人口老龄化和日益虚弱。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设备上时，它们会成长为一个被糖衣覆盖的细胞群落，称为生物膜，对抗生素或消毒剂的杀戮变得高度抵抗。生物被膜感染很常见，很难用传统的抗生素治疗，通常需要移除受感染的医疗设备。许多微生物也对我们有限的抗菌素产生了抗药性，因此迫切需要新的方法来预防医疗器械的感染。我们建议设计一种能够抵抗微生物定植的生物材料，这是生物膜形成的第一步，也是必不可少的一步。这种生物材料将覆盖有旨在排斥蛋白质(帮助微生物结合)并释放免疫调节化合物一氧化氮(NO)的化学物质。NO既有加速组织愈合的优点，也有阻止细菌附着到未洗脱表面的优点。这种生物材料将在不使用抗生素的情况下进行测试，以确定其在促进愈合的同时阻止微生物结合的能力。我们计划使用一系列生物物理、生化和微生物学技术来测试其机械和生物性能，最终在将材料转化为人类使用之前在动物模型中测试材料的安全性。

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.