Development of Hemocompatible, Zwitterionic Poly(sulfobetaine methacrylate) Surface Coatings by ARGET ATRP for Extracorporeal Applications

Abstract

Surface modification of blood-contacting medical devices is essential to prevent complications such as thrombosis and to prolong their usable lifetime, thus improving patient outcomes and reducing the need for potentially risky replacements. Extracorporeal membrane oxygenation machines have some of the largest artificial (non-endothelialized) surface area over which significant volumes of patient blood continuously flow. Unlike native blood vessels, these surfaces present contacts that lack the ability to mitigate blood coagulation. Hence, the materials are often modified to expose anticoagulant biomolecules that can inhibit clotting factors and/or biocompatible polymers that can physically prevent platelet and protein adhesion. In this work, zwitterionic antifouling poly(sulfobetaine methacrylate) (polySBMA) coatings were applied to two brands of commercially available medical-grade extracorporeal polyvinyl chloride (PVC) tubing using an atom transfer radical polymerization process initiated by activators regenerated by electron transfer. The effects of initiator immobilization reaction conditions were investigated to establish favorable conditions for consistently producing polySBMA coatings, with Fourier transform infrared spectroscopy employed for measuring differences in coating thickness. Plasma recalcification time assays were conducted to establish the antithrombogenic performance of the coatings via coagulation cascade activation times in the absence of platelet effects. Generated polySBMA coatings on PVC yielded prolonged clotting times under static conditions, albeit with some variability, demonstrating the potential of this approach. Future work involving dynamic coagulation testing would offer a more comprehensive assessment of the utility of polySBMA-coated PVC tubing in extracorporeal circuits.