Citations

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 Background and Aims Stroke and systemic embolism are recognized but poorly characterized complications of atrial fibrillation (AF) and left atrial flutter (AFL) catheter ablation. Their incidence, outcomes, and procedural associations remain insufficiently defined. Methods Retrospective global registry was initiated by the European Heart Rhythm Association Scientific Committee. A secure database captured data from ablation centres worldwide on general AF and left AFL ablation activity, as well as detailed information on patients with symptomatic embolic events between 2017 and 2024. Results Overall, 204 centres reported 335 743 ablation procedures and 550 embolic events (incidence 0.16%). Centre-level rate ranged from 0% to 3.1%. Most events were cerebral (94%), followed by peripheral (5%), and combined (1%). Coronary air embolism accounted for 62% of all peripheral events. Intraprocedural events occurred in 93 patients (17%), within 72 h in 357 (78%) and beyond 72 h in 100 (22%); 128 cases (23%) were diagnosed after hospital discharge. Nonparoxysmal AF (0.23% vs 0.15%; P < .001), centre experience, and ablation energy source (radiofrequency, 0.16%; cryoballoon, 0.16%; pulsed field ablation, 0.25%; laserballoon, 0.88%; P < .001) were associated with embolic risk. Median NIHSS score after stroke was 4 (interquartile range, 2–9). Three-month follow-up was available for 518 patients with embolism (95%): 181 (35%) had sequelae and 16 (3%) died. Conclusions Symptomatic embolic events are infrequent but associated with significant morbidity and mortality. Most events occur early, though a substantial proportion arise later. Higher event rates were observed with laser and possibly with pulsed field ablation. A greater centre experience was associated with a lower embolism incidence.

High insertion torque can cause conventional bioactive implant coatings to delaminate, generating debris and compromising osseointegration. We developed and evaluated an injectable, self-assembling peptide nanofiber interface designed to be applied in the osteotomy site to enhance biomechanical stability and accelerate bone formation. A multifunctional, injectable gel was formed from self-assembling peptide amphiphiles designed to be osteoinductive, adhesive, and antimicrobial. In a rabbit model, custom titanium implants were placed with either the nanofiber interface or a standard sand-blasted, large-grit, acid-etched (SLA) surface. Osseointegration was evaluated at 3 and 5 wk using micro–computed tomography (micro-CT) for bone-to-implant contact (BIC) and bone volume/total volume (BV/TV), as well as biomechanical reverse torque testing. At 5 wk, implants with the nanofiber interface demonstrated significantly superior osseointegration. BIC reached 58.7% compared to 50.5% for SLA-treated implants ( P < 0.001). BV/TV was also significantly higher at 51.8% versus 42.6% for the SLA group ( P < 0.001). Crucially, biomechanical stability was markedly improved, with the nanofiber group withstanding a reverse torque of 53.2 N·cm, significantly higher than the 41.8 N·cm for the SLA group ( P < 0.01). This injectable nanofiber interface successfully overcomes the limitations of traditional coatings by enhancing bone–implant integration and providing superior biomechanical stability. Uniquely, it is designed to prevent or repair drilling-induced microdamage, occupy peri-implant microcracks with a structural nanoscaffold, and act as a flowable, conformal osteotomy liner when applied prior to implant insertion. This practical approach represents a promising strategy to improve long-term clinical outcomes, particularly in patients with compromised bone quality or a higher risk of implant failure.

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 Untethered mobile milli/microrobots hold transformative potential for interventional medicine by enabling more precise and entirely non‐invasive diagnosis and therapy. Realizing this promise requires bridging the gap between groundbreaking laboratory demonstrations and successful clinical integration. Despite remarkable technical progress over the past two decades, most millirobots and microrobots remain confined to laboratory proof‐of‐concept demonstrations, with limited real‐world feasibility. Here, we identify key factors that slow translation from bench to bedside, focusing on the disconnect between technical innovation and meaningful patient outcomes. We argue that the long‐term impact and sustainability of the field depend on aligning development with unmet clinical needs, demonstrating feasibility, value and integration potential into existing clinical workflows. To foster translational research of milli/microrobots, we introduce a strategic milli/microrobot Technology Readiness Level framework (mTRL), which maps system development from initial conceptualization to clinical adoption through clearly defined milestones and their associated stepwise activities. The mTRL model provides a structured gauge of technological maturity, a common language for multi‐disciplinary collaboration and actionable guidance to accelerate translational development toward new, safer and more efficient interventions.

Purpose: Cutaneous squamous cell carcinoma has a propensity for perineural invasion. Treating perineural spread has involved surgery and adjuvant chemoradiation, and more recently, immune checkpoint inhibitors. This study aims to evaluate motor and sensory functional outcomes in patients with cranial neuropathies from perineural spread of squamous cell carcinoma, particularly those undergoing immunotherapy. Methods: This was a multicenter case series and literature review. Results: Eighteen patients with cranial neuropathies from perineural spread had a mean age of 72.5 ± 9.7 years. Cranial nerves V and VII were most often involved. Treatments included radiotherapy (8/18; 44.4%), chemotherapy (7/18; 38.9%), and/or immunotherapy (11/18; 61.1%), with many receiving a combination of modalities (8/18; 44.4%). Of those receiving immunotherapy, 72.7% (8/11) demonstrated at least partial clinical and/or radiologic tumor response. Among those with functional outcomes documented, half had improvement in sensory/motor nerve function following immunotherapy (4/8; 50%). A literature review identified 55 articles describing 449 patients total with cranial neuropathies from squamous cell carcinoma perineural spread. Combinations of surgery, chemotherapy, and/or radiotherapy were employed, with immunotherapy used in 16 patients. From 5 patients on immunotherapy with documented functional outcomes, all demonstrated at least some improvement. Conclusion: Immunotherapy plays an evolving role in managing advanced squamous cell carcinoma. Functional improvements in cranial neuropathy were demonstrated in 50% of patients receiving treatment with immunotherapy at a mean of 32.6 months of follow-up. This may hold important implications for the timing of surgical intervention, particularly in the case of cranial nerves V and VII palsies.

Abstract Background Frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominant atrophy is an emerging area of interest. Recent findings by the International Working Group (IWG) have identified this subtype as having a distinct clinical profile within the FTD spectrum (Ulugut et al., 2024, A&D). However, its genetic and pathological underpinnings remain unexplored in large, multicultural cohorts. Methods Retrospective analyses encompassing clinical, genetic, pathological, and neuroimaging data from 23 IWG sites across 13 countries in Asia, Middle East, Europe, North and South America were conducted. The study included 444 patients with FTD exhibiting predominant RATL atrophy. Results Genetic screening was performed on 51% ( n = 225) of the cohort for at least the major frontotemporal lobar degeneration (FTLD) mutations including microtubule‐associated protein tau ( MAPT ), progranulin ( GRN ), and chromosome 9 open reading frame 72 ( C9orf72 ), or dementia panels encompassing extended sets of genes. Of these, 81% were sporadic, showing negative results for the screened genes and a modified Goldman Score of ≥ 3, indicating a negative family history for dementia. The MAPT mutation was the most common genetic variant, identified in 7% of the screened cases (Figure 1). Pathological confirmation was available for 63 patients. Among the sporadic cases, transactive response DNA‐binding protein 43 type C (TDP‐C) pathology was most prevalent (60%, n = 32), while tau‐MAPT pathology was most common in the genetic cases (38%, n = 16). Fifteen cases did not fit neatly into genetic or sporadic categories, displaying heterogeneous pathologies (Figure 2). At the initial visit, compared to genetic cases, patients with TDP‐C pathology were older, and more frequently exhibited semantic deficits, with less frequent attention difficulties and executive dysfunction. No differences were observed in sex distribution, symptom duration or disease severity between genetic and sporadic TDP‐C cases. However, left handedness was more common in TDP‐C cases (14%) compared to genetic cases (5%). Conclusion While FTD with RATL atrophy primarily appears sporadic, a significant proportion of cases exhibit genetic variants. These sporadic and genetic subtypes display distinct neuropathological features and clinical manifestations. Given the implications for therapeutic strategies, precise clinical and molecular subtyping is critical for enhancing patient management and ensuring appropriate enrollment in clinical trials.

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.