Netanel Korin

Intracranial aneurysms (IAs) are life-threatening cerebrovascular malformations in which complete and durable sac closure is the primary goal of endovascular treatments, including coiling, stent-assisted coiling and flow-diverter implantation. However, standard catheter-based approaches may fail to fully occlude the sac and are limited by the need for direct access. Liquid embolic agents offer better geometric conformity, but their deployment remains constrained by similar access issues. In this study, we present a gravity-driven approach for distal filling of IAs. Through a combination of analytical modelling, in vitro experiments with idealized aneurysm models, and patient-specific computational fluid dynamics (CFD) simulations, we demonstrate that efficient filling of aneurysm cavities from relatively remote locations may be achieved using a heavier injectable fluid, while properly adjusting tilt angle and injection flow rate. A phase diagram of flow regimes highlights the interplay between gravitational, inertial and viscous forces critical to successful filling. Our findings show that slow, gravity-assisted injections minimize bypass and spillover, enabling targeted aneurysm filling even in complex geometries. CFD simulations highlight the need for patient-specific planning of such a procedure accounting for personal vascular anatomy. This strategy may provide a safer and less invasive alternative to current endovascular techniques, especially for anatomically inaccessible aneurysms.

Purpose: Polymeric heart valves (PHVs) remain limited by adverse leaflet mechanics and durability challenges. This study investigated biomimetic fiber reinforcement to improve leaflet mechanics while limiting effects on valve function. Methods: Polycarbonate urethane (PCU) leaflets containing encapsulated polyethylene terephthalate glycol (PETG) fibers were fabricated by multi-material 3D printing and heat-assisted compression. Unreinforced, horizontal, ply, and biomimetic configurations were evaluated by finite element (FE) analysis at 0.3-mm and 0.2-mm leaflet thicknesses. Characterization included notched testing and scanning electron microscopy. Pulse duplicator testing of 0.2-mm valves measured geometric orifice area (GOA), effective orifice area (EOA), and regurgitation fraction (RF). Results: The manufacturing approach produced embedded reinforcement architectures, and microscopy confirmed that fibers remained encapsulated, with no visible interfacial debonding after short-term hydrodynamic loading. Notched testing showed orientation-dependent behavior; 45° reinforcement increased maximum nominal ligament stress relative to unreinforced PCU. Reinforcement redistributed leaflet loading, with effects more pronounced at reduced thickness. The biomimetic configuration yielded the lowest predicted strain energy density, 22% and 26% lower than in unreinforced 0.3- and 0.2-mm valves, respectively. Experimental GOA measurements followed the FE trend. Although reinforcement reduced GOA, EOA differed modestly among configurations, while RF did not differ significantly. Overall, the biomimetic architecture provided the most favorable balance between mechanical response and valve opening among reinforced designs. Conclusions: Biomimetic fiber reinforcement reduced predicted leaflet mechanical demand, particularly in strain energy density, while limiting its effect on valve performance. Leaflet thickness and reinforcement architecture should be optimized jointly to balance mechanical support and valve function.

Background: Stent thrombosis is a serious complication of angioplasty with stenting, as evidenced by the associated morbidity and mortality events. Its incidence is particularly elevated after emergent carotid stenting in patients with acute ischemic stroke, reaching 20%. A better understanding of the mechanisms driving stent thrombosis will open up new avenues to limit this alarming complication. Its 2 main determinants are the ruptured atherosclerotic plaque and the stent itself, whose particular role in the process remains unknown. Methods: Using a new macrofluidic model mimicking the geometry of the human carotid artery, the intrinsic thrombogenicity of carotid stents was evaluated. Results: Real‐time video microscopy combined with scanning electron microscopy revealed that the Casper and the Wallstent, 2 widely used commercial stents, are thrombogenic and promote the formation of a massive thrombus in the carotid bifurcation (Casper: median, 9 [interquartile range, 6.4–24.4]×10 ⁵ μm ² ; Wallstent: median, 9.5 [interquartile range, 1.5–20.8]×10 ⁵ μm ² ). This result was consistent with a retrospective clinical study in stented patients with tandem lesions, in which 21.1% presented stent thrombosis, and 38.7% of these cases occurred at the bifurcation. Moreover, a stent lying in the carotid bifurcation of the macrofluidic model generated a prothrombotic high‐shear environment, triggering thrombosis, which was prevented in the presence of aspirin or abciximab. Finally, stents with a new design could avoid the formation of large thrombi in the carotid bifurcation (full stent: median, 8.9 [interquartile range, 7.8–17.2]×10 ⁵ μm ² ; stent with an opening at the bifurcation: median, 2.1 [interquartile range, 1.1–3]×10 ⁵ μm ² ), opening up the perspective of new ways to prevent carotid stent thrombosis. Conclusions: Stents placed inside the carotid bifurcation are responsible for a massive thrombus formation that could lead to stent thrombosis. The absence of mesh prevents its formation.

Red blood cells (RBCs) are widely utilized as natural drug delivery systems due to their unique mechanical properties, which enable prolonged circulation and physiological function. This study examines a biophysical strategy that employs shear‐responsive RBC (sr‐RBC) carriers to mechanically release drugs at stenotic arteries. Intracellularly loaded sr‐RBCs exhibited shear‐dependent cargo release when perfused through stenotic arterial models, while no release was observed in unconstricted vessels. Notably, the sheared sr‐RBCs retained their membrane integrity and CD47 expression while maintaining their ability to traverse microvascular networks without release when perfused through a microfluidic model simulating pulmonary capillaries. Multiscale modelling of RBC suspension fluid dynamics demonstrates a strong positive correlation between the sr‐RBC drug release and the overall RBC membrane stretching induced by the high shear rates at various stenotic percentages. Sr‐RBCs and mechanosensitive cell carriers may enable new avenues for treating life‐threatening arterial constrictions and other vascular diseases.

Device‐associated thrombosis remains a critical problem in cardiovascular medicine, often requiring lifelong anticoagulation therapy that paradoxically introduces significant bleeding risks. Here, we present a bioinspired passive flow routing approach that mitigates thrombosis by altering local hemodynamics to reduce stagnation, a primary hemodynamic driver of clot formation. Inspired by flow‐reattachment mechanisms in avian wings and aeronautical slats, we integrate circumferential routing channels into mechanical heart valve housings to redirect a small fraction of forward flow into peri‐ring regions prone to stasis. Computational optimization identifies a configuration that eliminates near‐zero‐shear pockets and reduces exposure to low shear by several orders of magnitude, while maintaining comparable high‐shear exposure relative to control under physiologic conditions. In a fibrin clot deposition assay, the routed design exhibits reduced peri‐ring clot accumulation. In an ovine bypass model without anticoagulation, the routed valve demonstrated improved sinus washout across angiographic assessments and, unlike the control, explant examination after three months showed no macroscopic thrombus at the sewing‐ring interface. Preliminary computational extensions indicate that passive flow routing can alleviate stagnation in additional cardiovascular geometries. These findings establish bioinspired passive flow routing as a hemodynamic design strategy to mitigate thrombosis in cardiovascular devices by targeting the hemodynamic root cause of stasis.

Since their inception, DNA origami nanostructures (DONs) have attracted great interest for their programmable geometry, nanoscale precision, and biocompatibility. Here, we present mechanoresponsive DONs designed for targeted drug delivery to narrowed or obstructed arteries. Unlike conventional systems triggered by biochemical cues or external stimuli, our capsules respond autonomously to elevated local shear forces characteristic of stenotic blood flow. The design consists of a hollow boxlike structure sealed by two lids connected through flexible DNA springs, enabling mechanical opening under pathological flow conditions. The nanostructures were assembled and characterized by atomic force microscopy and cryo-transmission electron microscopy, and the mechanical response of the DNA springs was evaluated using optical tweezers. The results confirm that the capsules can operate within physiologically relevant force ranges, demonstrating their potential for noninvasive, site-specific drug release. This mechanoresponsive strategy offers a new paradigm for smart, force-activated nanocarriers for targeted diagnosis and therapy.

Central nervous system diseases pose a significant challenge for the development of effective drugs and therapies. A major limiting factor is the neurovascular unit (NVU), which is both anatomically complex and characterized by a highly selective barrier. Conventional 2D in-vitro models and in-vivo animal models do not adequately replicate its pathophysiology. Organ-on-a-Chip technology provides a powerful platform to model the NVU, enabling replication of its anatomical and functional features within a dynamic microenvironment that closely mimics the human brain. However, the requirement for specialized facilities and technical expertise limits accessibility, reducing broader translational applications. Additionally, conventional endpoint analyses constrain real-time monitoring of cellular behavior. Here, we present and validate a novel bi-modular microfluidic chip that offers an easy-to-use and scalable solution for studying cellular cross-talk, while enabling live imaging and real-time measurements. The model incorporates human endothelial cells and primary neurons that were investigated through immunofluorescence and live imaging. The design overcomes key fabrication challenges and integrates a simplified method for Trans-Epithelial/Endothelial Electrical Resistance (TEER) monitoring, allowing in situ real-time assessment of barrier integrity. Overall, this platform represents a robust and versatile tool for in-vitro studies of the NVU, facilitating comprehensive evaluation of its structural and functional dynamics. Our microfluidic NVU-on-chip represents a significant advancement in NVU modelling, providing a versatile platform for CNS drug screening, disease modelling, and personalized medicine applications.

Injectable hydrogels are promising biomaterials for treating aneurysms, life‐threatening blood‐filled saccular lesions, enabling complete filling of the aneurysm and supporting tissue repair. Yet, the challenge is to enable clinical translation as hydrogels must not protrude into the parent vessel, nor migrate from the aneurysm cavity. Here, injectable, negatively‐charged, biologically and mechanically compatible hydrogels with environment‐sensitive swelling capabilities that cease swelling upon contact with blood are developed. Hydrogels are fabricated by copolymerizing sodium 2‐acrylamido‐2‐methylpropanesulfonic acid (NaAMPS) and 3‐sulfopropyl acrylate (KSPA) by using polyethylene glycol diacrylate (PEGDA). Three formulations (2%, 4%, and 6%) demonstrating a wide range of physiological‐relevant stiffnesses are fabricated. The selected mechano‐compatible 4% hydrogel exhibits a suitable swelling pressure (125 kPa) and supports high endothelial cell viability (> 75%). Importantly, the hydrogel demonstrates a significant differential swell with respect to blood (30 ± 4%), plasma (58 ± 3%), and PBS (82 ± 2%). This environment‐selective swelling, upon exposure to blood, results in minimal directional swelling toward the parent artery, which can improve embolization outcomes. Hydrogel embolization in 3D‐printed aneurysm models subjected to physiological blood flow shows no protrusion toward the main artery while completely blocking flow into the aneurysm. This approach provides promising opportunities for efficient embolization of a variety of aneurysms and vascular malformations.