Treatment of Ruptured Wide‐Necked Aneurysms using a Microcatheter Injectable Biomaterial

Abstract

Ruptured wide‐neck aneurysms (WNAs), especially in a setting of coagulopathy, are associated with significant morbidity and mortality. We show that by trapping a sub‐millimeter clinical catheter inside the aneurysm sac using a flow diverter stent (FDS), we can achieve instant hemostasis by filling the aneurysm sac using a novel biomaterial rescuing catastrophic bleeding in large animal models. Here, multiple formulations of a biomaterial comprising gelatin, nanoclay, and iohexol were developed, optimized, and extensively tested in vitro to select the lead candidate for further testing in vivo in rat, porcine and canine models of WNAs, including in a subset with aneurysm rupture. The catheter‐injectable and x‐ray visible versions of the gel embolic agent (GEA) with the optimized mechanical properties outperformed control groups, including a subset that received a clinically used liquid embolic (Onyx, Medtronic), with and without aneurysm rupture. A combinatorial approach to ruptured WNAs with GEA and FDS may change the standard of medical practice and save lives.This article is protected by copyright. All rights reserved

Development of an Injectable, ECM-Derivative Embolic for the Treatment of Cerebral Saccular Aneurysms

“…Recently, extensive research has been conducted on gelatin for the development of injectables aimed at treating hemorrhage. Gelatin has been explored as a shear-thinning, 11−15 semisolid, 16,17 and cross-linkable hydrogel. 18,19 These studies have been motivated by the various characteristics of gelatin, such as its ability to trigger clot formation, low immunogenicity, and support for cell attachment and proliferation.…”

“…Among these approaches, injectables composed of gelatin and nanoclay have shown promising results in hemorrhage control and embolization. 16,17 However, it has been reported that silicate nanoplatelets can induce cytotoxicity through the generation of reactive oxygen species, damage to cell membrane interactions, and intracellular interaction mechanisms. 20 In light of these concerns, the development of extracellular matrix (ECM)-derived cross-linkable hydrogels, such as those based on modified gelatin and hyaluronic acid, has garnered attention as injectable gels due to their cytocompatibility, biological functionality, and slow degradability relative to physically cross-linked gels.…”

“…Recently, extensive research has been conducted on gelatin for the development of injectables aimed at treating hemorrhage. Gelatin has been explored as a shear-thinning, − semisolid, , and cross-linkable hydrogel. , These studies have been motivated by the various characteristics of gelatin, such as its ability to trigger clot formation, low immunogenicity, and support for cell attachment and proliferation. Among these approaches, injectables composed of gelatin and nanoclay have shown promising results in hemorrhage control and embolization. , However, it has been reported that silicate nanoplatelets can induce cytotoxicity through the generation of reactive oxygen species, damage to cell membrane interactions, and intracellular interaction mechanisms …”