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

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Magnetically controlled hydrogel microrobots (HydroBots) were developed to navigate into thrombi and enhance targeted thrombolytic drug delivery, achieving better recanalization in a preclinical model than drug administration alone.

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The paper investigates magnetically guidable soft hydrogel microrobot swarms (HydroBots) designed to deliver thrombolytics into the adjacent no-reflow region of thrombi, using computational modeling, in vitro assays, and an in vivo preclinical porcine renal artery thrombus-occlusion model. Using HydroBots made of a dextran shell with iron oxide nanoparticle chains and an anisotropic ~10 µm size, the authors report that modeling predicts navigation into the no-reflow region, and experiments show biocompatibility/hemocompatibility with no immunogenicity and improved thrombolytic efficacy when HydroBots are combined with tPA, achieving better recanalization than tPA alone across multiple tPA doses that are lower than total clinical dosing. The authors acknowledge that the work is a preprint and not yet peer reviewed. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Abstract 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.
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Open-Loop Control of Soft Hydrogel Microrobot Swarms for Targeted Thrombolysis in a Preclinical Model | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Open-Loop Control of Soft Hydrogel Microrobot Swarms for Targeted Thrombolysis in a Preclinical Model Simone Schuerle, Yimo Yan, Josh Mosfin, Tim Grossrieder, Gian-Andrea Burkard, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8923535/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract 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. Physical sciences/Engineering/Biomedical engineering Health sciences/Cardiology/Cardiac device therapy Full Text Additional Declarations Yes there is potential Competing Interest. Simone Schuerle is co-founder and member of the board of Magnebotix AG. Supplementary Files SupplementaryInformation.pdf Supplementary Information Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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