Urbina, Pamela A. Manco

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.

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.