Blood-contacting devices are commonly coated with antithrombotic 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 antithrombotic catheter surface treatment is developed using oligodeoxynucleotide (ODN) toehold exchange. ODN strands modified to carry antithrombotic payloads can inhibit the 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 antithrombotic payload. This study presents a unique strategy for achieving a continuous antithrombotic state for blood-contacting devices using an ODN-based regeneration method.
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