Biomimetic Glycosaminoglycan‐Analog Hydrogel for Improved Embolization of Aneurysms: Environment‐Selective Swelling

Abstract 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.