Anti-Thrombogenic Carboxybetaine Surface Modification

Infection and thrombosis of vascular catheters afflict hundreds of thousands of patients each year and add billions of dollars in excess healthcare expenses. The cause of these complications can ultimately be linked to interactions between the catheter surface and both bacteria and blood components. Existing antimicrobial or heparin coating technologies have made advances in addressing short-term complications, but there is an unmet need for more efficacious and longer lasting surface technologies which don't utilize potentially toxic agents.

Semprus BioSciences is developing novel surface modifications based on non-leaching carboxybetaine (CB) polymers. CB polymers are zwitterionic, highly water-coordinating materials incorporating a monomeric unit derived from glycine betaine, a known anti-thrombotic agent. Acrylamide polymers of CB promise increased stability in vivo as compared to PC or PEG based materials due to the lack of cleavable ester or ether bonds either in the polymer backbone or side chain.

Significant data has been generated to-date on CB formulations demonstrating the potential to reduce both bacterial biofilm formation and protein and cell adhesion. Recently these chemistries were adapted to medical-grade polyurethane (Tecoflex®) using a UV-grafting method. Samples were then tested in a widely utilized model of thrombosis, in which 10Fr x 10cm treated rods were subjected to a flow loop of fresh bovine blood. After two hours, CB samples showed a marked visual decrease in thrombosis and an 80% decrease in the attachment of radio-labeled platelets.

These results demonstrate that CB polymers show great promise as surface treatments to prevent both thrombosis and medical device infection without the use of potentially harmful substances such as antibiotics or heparin.