Regenerating Antithrombotic Surfaces through Nucleic Acid Displacement

Blood-contacting devices are commonly coated with anti-thrombotic agents to prevent clot formation and to extend the lifespan of the device. However, in vivo degradation of these bioactive surface agents ultimately limits device efficacy and longevity. Here, a regenerative anti-thrombotic catheter surface treatment is developed using oligodeoxynucleotide (ODN) toehold exchange. ODN strands modified to carry anti-thrombotic payloads can inhibit thrombin enzyme when bound to a surface and exchange with rapid kinetics over multiple cycles, even while carrying large payloads. The surface-bound ODNs inhibit thrombin activity to significantly reduce fibrinogen cleavage and fibrin formation, and this effect is sustained after ODN exchange of the surface-bound strands with a fresh anti-thrombotic payload. This study presents a unique strategy for achieving a continuous anti-thrombotic state for blood-contacting devices using an ODN-based regeneration method.