(368be) Development of a Hemocompatible, Zwitterionic Surface Coating for Extracorporeal Medical Tubing

Juliana graduated with her Master of Science in Chemical Engineering from Vanderbilt University in May 2024, where she worked at the Bioinspired Materials and Surfaces Lab under the direction of Drs. Paul Laibinis and Kane Jennings. Her thesis research was focused on the development of hemocompatible, zwitterionic polymer surface coatings by ARGET ATRP for extracorporeal applications. Juliana also holds a Bachelor of Science in Biomedical Engineering, with a concentration in biomaterials and tissue engineering, from the New Jersey Institute of Technology. She has 7 years of research experience in materials science, microfluidics, and nanotechnology and is eager to explore opportunities in medical devices, pharmaceutical manufacturing, and chemical production (particularly polymers). Moreover, Juliana is an alumna of the National Science Foundation Innovation Corps National Teams program and has conducted customer discovery for technologies in various areas, including environmental monitoring and biotechnology.

Problem

Polyvinyl chloride (PVC) is the dominant plastic used in medical tubing production, offering transparency for visual clot detection. However, its hydrophobicity allows protein adhesion, which is further exacerbated by the migration of plasticizers incorporated to impart flexibility. To address this issue, we have developed antifouling zwitterionic polymer coatings to delay or prevent blood-plasma coagulation on PVC tubing used in extracorporeal membrane oxygenation (ECMO) circuits.

Methods

Zwitterionic poly(sulfobetaine methacrylate) (polySBMA) coatings were produced on two brands of commercially available medical-grade PVC tubing by atom transfer radical polymerization (ATRP), initiated by activators regenerated electron transfer (ARGET). I specifically explored solution-phase and vapor-phase approaches to initiator immobilization to establish favorable conditions for producing polySBMA coatings with consistent properties. Chemical modification was confirmed via water contact angle measurements and attenuated total reflectance Fourier transform infrared (ATR-FTIR) analyses. Owing to the curvature and optical transparency of the PVC tubing, which limited the use of traditional ellipsometry for measuring film thicknesses, differences in coating thickness were estimated from FTIR bands associated with sulfonate groups in polySBMA. The hemocompatibility of polySBMA-coated PVC tubing was assessed via plasma recalcification time assays performed under static in vitro conditions.

Results

PolySBMA coating of a commercially available medical-grade PVC tubing selected for surface modification generally exhibited prolonged plasma clotting times compared to alternative commercially available options. Well-formed polySBMA coatings with consistently high wettability were achieved through a 2-minute solution-phase treatment of the initiator prior to surface-initiated ARGET polymerization of SBMA, while the longest plasma clotting times were observed on those resulting from 1-hour initiator vapor exposure before ARGET polymerization. The same procedures were applied to incorporate PolySBMA coatings on PVC tubing from another vendor, and although surface wettability increased, the tubing's already excellent clotting resistance did not improve, indicating a dependence on the PVC source and its manufacture.

Implications

These findings demonstrate the practical functionality of polySBMA coatings in enhancing the antithrombogenicity of ECMO circuits. Although wettability affects plasma protein-surface interactions, the uniformity of the thick polySBMA films on the PVC surfaces appeared to have a greater effect on plasma clotting time. The polySBMA coatings on PVC tubing examined in this work exhibited hydrophilicity and delayed coagulation times, albeit with some variability, demonstrating their potential efficacy as surface coatings. Further process development is necessary to replicate the properties of the polySBMA coatings on PVC across different manufacturers due to potential differences in tubing formulation.

Acknowledgement

Thank you to Dr. Justin Godown (formerly of Vanderbilt University Medical Center) for providing the commercial medical tubing; Dr. David Gailani (Vanderbilt University Medical Center) for supplying the materials and supplies for the coagulation studies; and Dr. Maxim Litvak for his guidance on conducting the plasma recalcification time assays.