Physiologically Adaptive Soft Millirobot for Atraumatic, Image-Guided Endovascular Therapy

Physiologically Adaptive Soft Millirobot for Atraumatic, Image-Guided Endovascular Therapy | 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 Physiologically Adaptive Soft Millirobot for Atraumatic, Image-Guided Endovascular Therapy Hakan Ceylan, Tuan Anh Le, Husnu Alabay, Prabh Singh, Melissa Austin, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8089047/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Atraumatic and localized drug delivery to the vascular endothelium remains a critical unmet need in interventional medicine, with major implications for the management of arterial and venous diseases. Current approaches, such as drug-eluting stents and drug-coated balloons, combine mechanical revascularization with local drug release but frequently denude the endothelium and injure vessel walls, leading to restenosis, thrombosis, and chronic inflammatory repair cycles that severely limit long-term outcomes. Here, we present EndoBot, a soft, untethered millirobot designed for atraumatic navigation and targeted endovascular drug delivery during physiologic blood flow. EndoBot employs magnetically actuated corkscrew propulsion and mechanically adaptive surface crawling to maintain low radial pressure (<1 kPa) and preserve endothelial integrity. Its feasibility is established in arterial and venous phantom models, ex vivo human umbilical veins under normothermic perfusion, and in vivo rat inferior vena cava, all under clinical fluoroscopic guidance using a human-scale magnetic manipulation system. Despite periodic vessel motion, compression, and geometric irregularities, EndoBot maintains stable, mechanically adaptive navigation without endothelial injury. Under real-time fluoroscopic imaging, we identify key challenges and showcase clinically feasible strategies for 3D localization and tracking, overcoming intrinsic depth limitations of 2D clinical imaging. The device can be deployed and retrieved through standard vascular sheaths and remains stable under supraphysiologic arterial and venous flow conditions (flow rate >100 mL min-1; flow velocity >155 cm s-1, shear stress >10 Pa). Blood-compatibility testing demonstrates no increase in coagulation tendency and minimal hemolysis (<0.01%) during magnetic actuation. For drug delivery, EndoBot employs a novel endoluminal painting-based technique that transfers a hydrophobic and flow-resistant coating directly onto the inner vessel surface. This method ensures uniform deposition of a biodegradable drug depot without generating fragments larger than typical capillary diameters (>10 mm). By enabling local, atraumatic drug delivery without compromising vessel wall integrity, EndoBot first time demonstrates a translationally viable platform for exploring effectiveness in preventive interventions in early-stage vascular disease and for adjunctive therapies in advanced disease stages. Physical sciences/Engineering/Biomedical engineering Physical sciences/Materials science/Soft materials/Polymers Full Text Additional Declarations Yes there is potential Competing Interest. T.A.L., H.H.A., S.M., and H.C. have filed a patent covering the technologies developed in this study. Supplementary Files 7SupMoviemov7.mp4 Endoluminal drug delivery 9SupMoviemov9.mp4 Navigation in vivo Part 2 1SupMoviemov1.mp4 Establishing operational limits for endovascular navigation performance 2SupMoviemov2.mp4 EndoBot stability under arterial and venous flow 5SupMoviemov5.mp4 Fluoroscopic-guided visualization, localization, and tracking in vitro 8SupMoviemov8.mp4 Navigation in vivo Part 1 4SupMoviemov4.mp4 Wireless deployment and retrieval 3SupMoviemov3.mp4 Propulsion demonstrations under multi-physics interference 10SupMoviemov10.mp4 Accidential navigation and device migration to rat heart 6SupMoviemov6.mp4 Atraumatic fluoroscopic navigation in perfused ex vivo human umbilical veins SupplementaryMaterials.docx Supplementary Information File Cite Share Download PDF Status: Posted 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8089047","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":543567928,"identity":"1b04bc5a-5a99-4a26-8c70-b301514d5aa6","order_by":0,"name":"Hakan 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Despite periodic vessel motion, compression, and geometric irregularities, EndoBot maintains stable, mechanically adaptive navigation without endothelial injury. Under real-time fluoroscopic imaging, we identify key challenges and showcase clinically feasible strategies for 3D localization and tracking, overcoming intrinsic depth limitations of 2D clinical imaging. The device can be deployed and retrieved through standard vascular sheaths and remains stable under supraphysiologic arterial and venous flow conditions (flow rate \u003e100 mL min-1; flow velocity \u003e155 cm s-1, shear stress \u003e10 Pa). Blood-compatibility testing demonstrates no increase in coagulation tendency and minimal hemolysis (\u003c0.01%) during magnetic actuation. For drug delivery, EndoBot employs a novel endoluminal painting-based technique that transfers a hydrophobic and flow-resistant coating directly onto the inner vessel surface. 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