Open-Loop Control of Soft Hydrogel Microrobot Swarms for Targeted Thrombolysis in a Preclinical Model

Thrombosis treatments, such as systemic administration of thrombolytics, suffer from poor efficacy and increased remaining-thrombus burden, resulting from a no-reflow zone adjacent to thrombi. Here we present the use of a magnetically guidable soft hydrogel microrobotic device, our HydroBots, which are comprised of a dextran shell and iron oxide nanoparticles chains. Their anisotropic shape and small size (10 µm) allow for ease of maneuverability to thus deliver systemic thrombolytics to break down thrombi. Computational models of the no-reflow region demonstrate HydroBots can navigate into the no-reflow region for effective drug delivery. In vitro tests show biocompatibility, hemocompatibility, and lack of immunogenicity for the HydroBots. Further in vitro tests reflect enhanced efficacy of thrombolytics with HydroBot administration compared to exclusive tPA injection. Finally, we perform in vivo tests in a thrombus-occluded porcine renal artery. Across various tissue plasminogen activator (tPA) doses, much lower than the total dose administered clinically, the HydroBots-tPA combination achieves better recanalization compared to tPA administration alone. Here, through safety and enhanced efficacy, our HydroBot demonstrates clinical promise as a novel solution for convection-enhanced thrombolytic drug delivery.