Farha, S. | bioRxiv Science

bioRxiv2026

Soft-Robotic Magnetic Microfluidic Catheter for Delivery of Aqueous-Based Dual-Component Embolic Formulations

Transcatheter embolization requires materials that can be steered through tortuous vessels, solidify rapidly in situ, remain clearly visible under fluoroscopy, and, ideally, carry therapeutic cargo without harming tissue. To meet these requirements, we present a fully water-based, two-component PEI-PEG hydrogel delivered through a soft-robotic, microfluidic catheter that keeps the precursors separate until they meet in a millimetre-scale mixing chamber at the tip. Fast amide cross-linking converts the liquid pair into a self-supporting gel within seconds, eliminating organic solvents and preventing catheter blockage. By adjusting precursor ratio and flow regime, the gel's stiffness and viscosity can be tuned over orders of magnitude, with the same chemistry allowing to occlude both high-flow arteries and fragile micro-vessels. The platform was validated in three escalating models. First, in ex-vivo perfused human placenta, the hydrogel filled targeted branches without reflux or fragmentation, demonstrating controlled delivery in clinically relevant vasculature. Next, in three porcine embolizations, splenic, hepatic and ascending pharyngeal arteries, the material achieved stable, selective occlusion with no migration, vasospasm or recanalization, showing seamless compatibility with standard interventional workflows. Finally, in rats bearing orthotopic liver tumours, drug-loaded hydrogel delivered through the hepatic artery concentrated doxorubicin inside tumours while sparing healthy tissue, confirming its potential for precision chemoembolization. These results position the PEI-PEG hydrogel and microfluidic catheter as a unified, image-guided platform that couples robust mechanical occlusion with site-specific drug delivery, offering a biocompatible alternative to current liquid embolics and expanding the therapeutic reach of minimally invasive embolization procedures.

bioengineering↗

bioRxiv2025

Hypoxia responses in arginase 2 deficient mice enhance cardiovascular health

RATIONALEPhysiological responses to hypoxia involve adaptations in the hematopoietic and cardiovascular systems, which work together to ensure adequate oxygen delivery to tissues for energy production. The arginine/nitric oxide (NO) pathway regulates both systems through its effects on erythropoiesis and vasodilation. In Tibetan populations native to high-altitude hypoxia, increased NO production from arginine and decreased arginine metabolism by arginase contribute to these adaptive mechanisms. These metabolic changes enhance tissue oxygen delivery and reduce the risk of hypoxic pulmonary hypertension. Here, we hypothesize that genetic deletion of mitochondrial arginase 2 (Arg2) in mice will enhance cardiovascular effects and mitigate hypoxia-induced pulmonary hypertension. METHODSComplete blood counts, bone marrow erythroid differentiation, plasma arginine and NO (measured as nitrite), right ventricular systolic pressure (RVSP), heart rate, heart weight, and blood pressure were measured in wild-type (WT) and Arg2 knockout (Arg2KO) mice exposed to short-term (6, 12, 48, or 72 hours) or long-term (3 weeks) hypoxia. RESULTSUnder normoxic conditions, Arg2KO and WT mice exhibit similar RBC counts, hemoglobin levels, hematocrit, heart rate, systolic and diastolic blood pressures, and heart weight (all P > 0.05). WT mice increase erythropoiesis at 12 hours of hypoxia, including proerythroblasts (stage I, P = 0.004), polychromatic erythroblasts (stage III, P = 0.0004), and orthochromatic erythroblasts (stage IV, P = 0.03), but Arg2KO mice do not increase erythropoiesis. After 48 hours of hypoxia, Arg2KO mice increase proerythroblasts (stage I, P = 0.0008), but levels remain significantly lower than in WT mice. Plasma arginine and NO levels increase under hypoxia. NO levels peak at 12 hours of hypoxia in WT mice, then decline rapidly. In contrast, NO levels in Arg2KO mice are higher than in WT mice, with sustained elevations at 48 hours of hypoxia (P = 0.03). Arg2KO mice have significantly higher plasma arginine levels than WT at 6, 12, and 72 hours of hypoxia (all P < 0.05). Under chronic hypoxia, Arg2KO and WT mice show similar RBC counts, hemoglobin levels, hematocrit, and NO levels. Unlike WT, Arg2KO mice do not increase RVSP (P = 0.4) and have lower mean arterial (P = 0.03) and diastolic blood pressures (P = 0.01), as well as much lower heart rates (P < 0.0001). Additionally, small blood vessels increase in lungs of Arg2KO mice (CD31, P = 0.02; vWF, P = 0.6). CONCLUSIONSArginine metabolism in the mitochondria plays a key role in modulating adaptive responses to hypoxia. Deletion of Arg2 results in delayed erythropoiesis under acute hypoxia, but better cardiovascular health, as indicated by higher levels of nitrite and arginine, and lower RVSP, blood pressure, and heart rate with chronic hypoxia.

physiology↗