High throughput discovery of novel polymers to prevent biofilm formation on blood-contacting medical devices

Biofilm formation on blood-contacting medical devices is a major healthcare problem causing significant morbidity, mortality and economic burden on healthcare systems around the world. In this thesis, a high throughput material microarray approach was used to screen a library of novel acrylate and methacrylate based polymer materials for bacterial attachment, haemostasis and immune system interactions. Polymer microarray printing was first optimised to produce confined spots of each material, confirmed by ToF-SIMS. The polymer microarray was incubated in human blood and analysed for blood proteins, cells and immune component attachment on each spot of the microarray. The blood exposed microarray was then incubated in RPMI-1640 media containing Pseudomonas aeruginosa and Staphylococcus aureus in two separate experiments to model a bacterial challenge on blood-contacting devices. These high throughput screening experiments identified nine haemocompatible bacterial resistant ‘hit’ materials for further analysis. The ‘hit’ materials identified from microarray screening were then scaled up and used as coatings on silicone catheters for further in-vitro bacterial attachment and haemocompatibility testing. The in-vitro bacterial attachment assays were similar to the assays carried out by Hook et. al. [1] with an added complication of blood pre-conditioning step to simulate blood-contacting devices. All of the scaled up materials showed a significantly lower surface bacterial attachment when compared with uncoated silicone and commercially available silver incorporated catheters. Co-polymer of isobornyl acrylate with tri(ethylene glycol) methyl ether methacrylate (75:25) showed 71% and 77% lower coverage of P. aeruginosa and 67% and 58% lower coverage of S. aureus when compared with uncoated silicone and silver incorporated catheters, respectively. A number of scaled up materials showed a good haemocompatibility, in particular the co-polymer containing 2-ethylhexyl methacrylate and di(ethylene glycol) methyl ether methacrylate (75:25), which showed a very low coagulation and immune system activation. The in-vivo foreign-body infection model results showed an order of magnitude reduction in bacterial attachment for co-polymer isobornyl acrylate (75%) tri(ethylene glycol) methyl ether methacrylate (25%) over five day period for P. aeruginosa and S. aureus when compared with a silicone surface. This reduction in bacterial numbers was also observed in the tissue surrounding the catheter. Furthermore, isobornyl acrylate–co-tri(ethylene glycol) methyl ether methacrylate also showed good biocompatibility without a foreign-body reaction. The future work involves testing these ‘hit’ materials in an animal model under blood flow conditions to validate in-vivo performance, a successful outcome of which would warrant a big step towards its clinical use