Peptides surface modification to prevent stent blockage

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DESCRIPTION (provided by applicant): Biliary stent blockage is the major complication of endoscopic stenting for the palliation of malignant obstructive jaundice. Bacteria adhere to the stent surface with their pili and also through the production of glycocalyx to form a bacterial biofilm. Biliary stents become blocked as a result of bacterial biofilm formation and accumulation of sludge within the lumen of the stent. Biliary sludge formed as a result of deconjugation of bilirubin diglucuronide by bacterial Beta-glucuronidase, resulting in the precipitation of calcium bilirubinate. This is attributed to enzymatic activities of aerobic bacteria such as E. coli and anaerobic bacteria such as C. perfringens. Different methods have been tried to prevent bacterial attachment and stent blockage including use of different plastic materials, changing stent designs, biocide impregnation and systemic antibiotic prophylaxis. However, none of these methods have produced significant clinical benefits. Small molecular peptides may influence the bacterial expression of gene/enzyme activities and affect their adherence characteristics. In this project, we explore the potential benefits of peptide surface modification using the "one-bead one-compound" combinatorial library method. This novel high through put technique can screen large numbers of different peptides that may affect bacterial adherence. In the first part of the experiment, we study the interaction between single bacteria E. coli and a mixed culture of E. coli and Enterococcus with a number of pre-generated peptide surfaces to identify peptide(s) that resist bacterial attachment. The amino acids sequence of these selected peptides are identified using automatic microsequencing. Large quantity of the specific purified resistant peptides are then synthesized and used to coat and modify plastic stents. The effects of these resistant peptide coated stents in delaying or preventing bacterial attachment is then tested with a special flow chamber or Modified Robbins Device. If significant benefit is observed with the in-vitro studies, a randomized controlled clinical study will be proposed to determine the benefits of the resistant peptide coated stents. The results may shed new lights in the prevention of chronic implanted medical device related infections and specifically in prolonging plastic stent patency.