Venous thrombosis (VT) is among the most prevalent medical problems today with an estimated annual incidence of approximately 1 million cases in the United States. Despite best medical therapy, there is often incomplete resolution of the DVT leading to fibrotic changes that clinically manifest as post-thrombotic syndrome (PTS). Up to 60% of DVT patients develop PTS, which increases the risk for DVT recurrence and can severely impact the quality of life causing chronic venous insufficiency and, at end stage, venous ulcers. We propose to develop endovascular catheters with flexible electrode arrays to deliver tunable non-thermal, low-voltage, pulsed electric fields (i.e., irreversible electroporatio (IRE)) to venous thrombus to prevent fibrotic changes so that enhanced physiologic breakdown of the clot can occur. Successful non-thermal ablation of the DVT cells may lead to complete physiologic resolution of the thrombus, decreasing the incidence of PTS. We propose to optimize intravascular non-thermal IRE using simple electrodes in a realistic 3D bioprinted thrombosed vessel-on-a-chip model (Aim 1). Using these IRE parameters, we will prototype catheters with flexible electrodes and test them in the thrombosed vessel-on-a-chip model (Aim 2) and in vivo in a rat DVT model (Aim 3). Successful completion of this study will show that pulsed, non-thermal IRE delivered by catheters coated with flexible electronics can prevent clot organization in a minimally invasive manner.
Fibrotic changes in venous thrombosis reduce the efficacy of anticoagulation therapy and catheter directed interventions leading to post-thrombotic syndrome (PTS). We propose to develop catheters containing flexible electronics to deliver non-thermal, low voltage electric fields to ablate the cells of the venous thrombus to prevent fibrosis, leaving the clot susceptible to physiological degradation.
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