(436g) Novel Functionalized Polyurethane Materials with Antimicrobial and/or Antithrombogenic Properties for Catheter Devices

Catheters are commonly introduced into the vasculature of a patient as part of an intravenous catheter assembly, including central venous catheters (CVCs), peripherally inserted central catheters (PICCs), and peripheral intravenous catheters (PIVCs). Polymer materials that have been considered for catheter tubing manufacturing include silicone rubber, polytetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP) copolymer, poly(ether-block-amide) copolymer, and thermoplastic polyurethane (TPU). Among these, TPU is the most used catheter tubing material due to its desirable physical properties (e.g., softening in vein) and biocompatibility.

Catheter-related blood stream infections (CRBSIs) and thrombosis-induced catheter occlusions are the two major issues related to catheter applications. CRBSIs are caused by colonization of microorganisms, which may occur in patients whose treatment includes intravascular access devices. Infections can lead to illness/fatality and significant cost burden to healthcare system. Moreover, synthetic plastics including polyurethanes have the potential of being thrombogenic causing blood clotting. Reduction of CRBSIs as well as catheter occlusions can significantly reduce healthcare costs as well as improve patient experience and clinician confidence.

In our work, we introduced various functional moieties into polyurethane formulations to render resulting functionalized TPU materials antifouling characteristics, including antimicrobial and antithrombogenicity. Firstly, anionic modifiers with –SO₃^- and/or –COO^- functional moieties were incorporated into the new TPU compositions, which can ionically bond cationic antimicrobial agents (e.g., chlorhexidine acetate) through a simple imbibing process. The new anionic TPU showed significantly higher chlorhexidine loading than the regular TPU and chlorhexidine loading is proportional to ionic content of the anionic TPU. The imbibed anionic TPU also showed a longer-term chlorhexidine elution, rendering this material great potential as a controlled release medical device. In addition, new anionic TPU materials possess very desirable thermal and mechanical properties, allowing them to be processed and used in various applications.

In another work, a perfluoropolyether (PFPE) modifier was incorporated into the new TPU compositions. As a result, the PFPE-modified TPU showed comparable bulk material thermal and mechanical properties, but a significant surface enrichment of the low surface energy fluoroether component to render the resulting fluorinated TPU materials lubricious and antithrombogenic surface properties. The new PFPE-modified TPU material was further evaluated for surface thrombogenicity in an in-vitro Chandler Loop model using fresh bovine blood, showing significantly reduced thrombus formation compared to the regular TPU material. This is presumably due to the function that hydrophobic and lubricious surface may passively reduce attachment of blood components, e.g., protein and fibrin sheath.

The implementation of these new anionic and/or fluorinated TPU materials in catheter devices can potentially prevent/reduce microbial colonization as well as thrombus and biofilm formation on/around the surface of polymeric catheter materials, thus reduce CRBSIs and thrombosis-induced catheter occlusions.