Alabay, Husnu Halid

ABSTRACT Human intestinal diseases, including inflammatory bowel disease (IBD), are difficult to model because existing animal and in vitro systems do not capture the intestine’s integrated vascular, immune, and metabolic complexity. Here, we establish a custom normothermic machine perfusion platform that maintains surgically resected human intestinal tissue for up to 72 hours under near-physiological conditions. Discarded specimens from patients with nonmalignant intestinal diseases, including IBD and diverticulitis, were continuously perfused at 37°C with real-time hemodynamic and metabolic monitoring. Perfusion preserved tissue viability, mucosal architecture, epithelial integrity, oxygen consumption, metabolic activity, and vascular patency. Daily perfusate sampling enabled longitudinal profiling and experimental modulation of inflammatory mediators, revealing patient-specific immune states. This long-duration platform bridges reductionist in vitro models and clinical disease, enabling mechanistic studies of intestinal inflammation and future testing of personalized therapies in intact patient-derived tissue.

Rotating magnetic fields (RMFs) are widely used to actuate untethered microrobots, yet delivering clinically relevant RMFs at human scale remains challenging. Here, we create a quantitative framework for human‐scale RMF delivery using robot‐arm‐mounted permanent magnets. It links anatomical separation, surface‐clearance constraints, magnet geometry, rotational inertia, and robot‐arm limitations to define a feasible RMF operating envelope. Magnet geometry is most important when target separation is comparable to magnet size; in this regime, diametrically magnetized cylinders provide the most efficient field delivery at constant magnet volume. At larger separations, field delivery converges toward dipole‐like scaling and becomes primarily governed by total magnet volume. Across the dominant microrobot operating envelope (5–30 mT, 1–30 Hz), required magnet mass ranges from sub‐kilogram values for limb and intracranial targets to more than 30 kg for deep thoracic access. As magnet size increases, rotational inertia rapidly emerges as the dominant mechanical constraint, with limb and intracranial targets remaining feasible whereas some thoracic scenarios exceed practical mechanical limits. We demonstrate a representative actuator designed within the proposed framework tested on a human‐scale vascular phantom under flow. This work provides a foundation for codesigning translational microrobots and their magnetic drive platforms tailored for relevant anatomical targets.

ABSTRACT Atraumatic and localized drug delivery to the vascular endothelium remains a critical unmet need in interventional medicine, with major implications for arterial and venous disease management. Here, we present EndoBot, an untethered elastic millirobot designed to enable endothelial‐safe, soft‐contact operation, under physiologic blood flow. EndoBot is magnetically actuated and navigates along the vessel lumen through curved, non‐uniform geometries while maintaining ultra‐low radial contact pressures (<1 kPa), far below endothelial injury thresholds. We demonstrate stable locomotion, with intrinsically compliant mechanics within a defined safety envelope under arterial and venous hemodynamics in phantom vessels, ex vivo human umbilical veins, and an in vivo rat inferior vena cava, without detectable vessel damage. EndoBot is compatible with standard vascular sheaths for wireless deployment and retrieval and is controlled under clinical fluoroscopic guidance using a human‐scale magnetic manipulation platform. Blood compatibility testing confirms safety, with minimal hemolysis and no increased coagulation tendency during navigation. For localized therapy, EndoBot employs a gentle endoluminal painting strategy, transferring a washout‐resistant drug depot directly onto the vessel lumen. By combining atraumatic mobility, clinical deployability, and localized drug deposition, EndoBot establishes a translationally viable platform for developingmaintenance‐oriented endovascular therapies, supporting prevention of restonosis, thrombosis and inflammatory remodeling following intervention.

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.

ABSTRACT Atraumatic and precise drug delivery to arteries and veins remains an unmet need in interventional medicine, with significant implications for managing vascular diseases and long-term patient outcomes. Conventional endovascular methods, such as drug-coated balloons and drug-eluting stents, often damage vessel endothelium and compromise wall integrity, leading to reduced therapeutic efficacy and severe complications including restenosis and thrombosis. To address these limitations, we introduce EndoBot, an untethered soft millirobot designed for atraumatic vessel navigation and localized drug delivery under physiological blood flow. EndoBot achieves this through magnetically actuated corkscrew propulsion and mechanically adaptive surface crawling, exerting low radial pressure (< 1 kPa) to preserve endothelial integrity. We validated its performance in phantom vessels, ex vivo human umbilical veins under normothermic perfusion, and in vivo rat inferior vena cava under fluoroscopic guidance using a human-scale magnetic manipulation platform. Despite dynamic vessel contractions and compressions along non-uniform cross-sections, mechanically adaptive locomotion strategy ensures safe navigation and protects the inner endothelial lining. EndoBot is deployable and retrievable via clinical vascular sheaths and remains stable even under supra-physiological blood flow conditions (> 155 cm/s). Extensive blood compatibility tests demonstrated minimal hemolysis (<0.01%), low platelet activation on the robot surface, and no increased coagulation tendency. For drug delivery, a hydrophobic transfer coating enables EndoBot to gently deposit a stable, flow-resistant drug layer onto the vessel wall without fragmentation. This novel platform enables safer and more effective targeted endovascular drug delivery, paving the way for transformative approaches to address early-stage vascular pathologies and deliver more effective preventive interventions.