Oxime hydrogels with ultrafast, pH-independent gelation for robust and adaptive vascular embolization

Vascular embolization is a key treatment for hemorrhages and tumors, yet conventional agents including coils and microspheres often suffer from incomplete filling, off-target embolism, and heavy dependence on systemic coagulation. While in situ-gelling liquid agents offer conformable filling, achieving robust gelation under high-shear hemodynamics without compromising distal penetration remains a translational hurdle. Here, we report a bioorthogonal oxime-ligation hydrogel engineered for robust and adaptive vascular embolization. This system is composed of aminooxy-functionalized gelatin (Gel-OA) and tetra-armed poly(ethylene glycol) aldehyde (4PEG-CHO), with gelatin-associated nucleophilic groups accelerating oxime-mediated network formation. This hydrogel system achieves rapid, robust gelation intra-arterially, enabling coagulation-independent embolization. Moreover, this design enables ultrafast gelation (within 5 s) even at low polymer concentrations (3.5-6% w/v) and demonstrates pH-independent gelation across a broad range (pH 2-9). Crucially, the low-viscosity precursors support catheter-based separated-stream delivery and deep penetration into the vascular bed before rapidly forming a cohesive network under flow. By varying the polymer concentration, the balance between distal penetration and local network fixation can be modulated. In vitro and in vivo models confirm precise, coagulation-independent occlusion without premature gelation or ectopic embolism. By penetrating vessels down to approximately 20 µm in diameter, the hydrogel enables distal microvascular embolization alongside stable proximal occlusion. This hydrogel system shows great promise for embolization therapy and other biomedical applications requiring rapid and spatially controlled solidification under dynamic physiological conditions.