Novel Rapid In Situ Curable PEGDA/PEG Composite Hydrogel Drives Biological Closure of Aneurysm Neck

<b>Background</b>: Endovascular treatments for cerebral aneurysms, including coil embolization, stent placement, and liquid embolization, are limited by recanalization, thrombosis-related risks, and insufficient biological regulation. <b>Methods</b>: A composite hydrogel based on poly-(ethylene glycol) diacrylate/poly-(ethylene glycol) (PEGDA/PEG) was synthesized by using a benzophenone/diphenylacetone (BP/DPA) photoinitiator system. Systematic in vitro characterizations were performed. For in vivo evaluation, carotid artery aneurysm models were established in white rabbits. Embolization outcomes were assessed using digital subtraction angiography (DSA) and color Doppler flow imaging (CDFI), while the underlying mechanisms were investigated through vascular tissue transcriptomic analysis and histological staining. <b>Results</b>: The 75 wt % PEGDA/PEG hydrogel achieved intravascular in situ curing within 60 s and exhibited a superhydrophilic surface with an appropriate elastic modulus. The hydrogel demonstrated excellent biocompatibility, promoted endothelial cell migration and vascular network formation, and enhanced CD31 expression. In vivo imaging confirmed complete aneurysm occlusion with the preservation of parent artery patency following embolization. Transcriptomic analysis identified claudin-1 (CLDN1) as a key regulatory gene, whose interaction with claudin-12 (CLDN12) and zonula occludens-1 (ZO-1) facilitated tight junction remodeling and endothelial migration at the aneurysm neck. <b>Conclusions</b>: This study demonstrates a bioactive embolization strategy integrating rapid in situ sealing, thrombus-independent embolization, and active biological repair, providing a conceptual framework for advancing aneurysm embolization materials from passive physical fillers to biologically driven therapeutic systems.