Dissolvable Sugar-Based Untethered Magnetic Millimeter-Scale Robot for Blood Clot Removal

Abstract

Thrombosis, or the formation of blood clots, is a potentially life-threatening condition that results in the complete or partial occlusion of a blood vessel. It remains one of the most prevalent causes of death worldwide. Current treatment approaches involve the intravenous administration of thrombolytic drug, which can increase the risk of uncontrolled bleeding, or catheter-directed treatments, which may have limited access to hard-to-reach areas of the vasculature and can cause catheter-related injuries. Untethered magnetic robots present an alternative approach for thrombosis treatment that addresses the current shortcomings. In this work, a rapidly dissolvable, millimeter-scale, magnetic robot is proposed for the delivery of thrombolytic drug for thrombus removal. The robot is composed of a sucrose-based material with embedded superparamagnetic iron oxide nanoparticles for magnetic control. Although assessment of the robot actuation showed limited forward propulsion from its helical structure, it was able to withstand a maximum flow rate of approximately 72 mL/min, which is comparable to the literature for small-scale magnetic robots. The mean dissolution time of the sucrose structure was 4.65 minutes. The blood compatibility of the robot material was measured through the upregulation of platelet activation markers and found to improve with decreasing material concentration. The drug delivery mechanism consisted of a sealed cavity along the center of the robot to maximize thrombolytic load and avoid drug exposure to high temperatures during fabrication. Release of a placeholder fluorescent protein was found to be gradual across the entire dissolution of the robot. To ensure the thrombolytic agent was not compromised upon loading into the robot, in vitro incubation with human thrombi was performed. The thrombolytic-loaded robot showed similar thrombus mass reduction compared to the direct administration of thrombolytic agent. Finally, the robot functionality was validated using an ex vivo endovascular thrombosis model of the sheep iliac arteries. The robot was clearly visualized under x-ray fluoroscopy due to its embedded magnetic material, enabling its guidance to the ex vivo thrombus via an external rotating permanent magnet mounted on a robotic arm. Successful navigation through a vascular bifurcation was demonstrated and robot mechanical action was shown to accelerate clot mass reduction. The effect of localized thrombolytic delivery on clot mass reduction in the ex vivo model was inconclusive. Overall, the proposed untethered and dissolvable robot would enable the localized delivery of thrombolytic agent to blood clots without the need for retrieval. This can lead to improved patient outcomes by reducing the risks of catheter-related injuries and uncontrolled bleeding resulting from the systemic administration of thrombolytic agents.