Douglas Weaver

Vascular Catheters with a Nonleaching Poly-Sulfobetaine Surface Modification Reduce Thrombus Formation and Microbial Attachment

Poly-sulfobetaine surface modification on a vascular catheter inhibits microbial adherence and thrombosis. Surface Modification Pulls Double Duty Marketing experts know that consumers can’t resist a good deal: Two-for-one; buy one, get one (or BOGO, if you’re up-to-date on your lingo); twice as nice, half the price. Similarly, engineers know that, if they can package twice the functionality in one medical device, they have a valuable product that clinicians cannot ignore. In this issue, Smith et al. designed one polymer coating for catheters that resolves two major challenges in biomaterials by preventing both blood clot accumulation (thrombosis) and bacterial adhesion (infection). Smith and colleagues created the zwitterionic polymer “polySB” (poly-sulfobetaine) surface modification, which, they hypothesized, can coordinate water and therefore resist protein adsorption and cell adhesion. PolySB was used to modify the inner and outer surfaces of common polyurethane peripherally inserted central catheters (PICCs). In vitro, the polySB-modified catheter reduced adherence and activation of human red and white blood cells compared with commercially available PICCs without the polySB surface. In addition, modified PICCs that had been soaked in serum for 60 days displayed no thrombus accumulation when exposed to bovine blood, thus demonstrating the long-term activity of the polySB. In vivo, in a canine model, polySB-modified PICCs had little thrombus accumulation: a reduction of ~99% compared to unmodified control devices. Last, polySB-modified PICCs showed up to 99.9% reduction in microbial attachment (both Gram-positive and Gram-negative bacteria) compared to unmodified PICCs; in rabbits, this translated to less inflammation. By preventing both infection and thrombosis, this multifunctional polymeric coating is just the BOGO the doctor ordered. Adherence of proteins, cells, and microorganisms to the surface of venous catheters contributes to catheter occlusion, venous thrombosis, thrombotic embolism, and infections. These complications lengthen hospital stays and increase patient morbidity and mortality. Current technologies for inhibiting these complications are limited in duration of efficacy and may induce adverse side effects. To prevent complications over the life span of a device without using active drugs, we modified a catheter with the nonleaching polymeric sulfobetaine (polySB), which coordinates water molecules to the catheter surface. The modified surface effectively reduced protein, mammalian cell, and microbial attachment in vitro and in vivo. Relative to commercial catheters, polySB-modified catheters exposed to human blood in vitro had a >98% reduction in the attachment and a significant reduction in activation of platelets, lymphocytes, monocytes, and neutrophils. Additionally, the accumulation of thrombotic material on the catheter surface was reduced by >99% even after catheters were exposed to serum in vitro for 60 days. In vivo, in a highly thrombogenic canine model, device- and vessel-associated thrombus was reduced by 99%. In vitro adherence of a broad spectrum of microorganisms was reduced on both the external and the internal surfaces of polySB-modified catheters compared to unmodified catheters. When unmodified and polySB-modified catheters were exposed to the same bacterial challenge and implanted into animals, 50% less inflammation and fewer bacteria were associated with polySB-modified catheters. This nonleaching, polySB-modified catheter could have a major impact on reducing thrombosis and infection, thus improving patient health.