In vivo embolization of lateral wall aneurysms in canines using the liquid-to-solid gelling PPODA-QT polymer system: 6-month pilot study

Abstract

Object Over the past 20 years, endovascular embolization has become the preferred method of treating cerebral aneurysms. While there are many embolic devices on the market, none is ideal. In this study the authors investigated the use of a liquid-to-solid gelling polymer system—that is, poly(propylene glycol) diacrylate and pentaerythritol tetrakis (3-mercaptopropionate) (PPODA-QT)—to embolize in vivo aneurysms over a 6-month period. Methods Experimental aneurysms were created in the carotid arteries of 9 canines. Aneurysms were embolized with the polymer only (PPODA-QT, 3 dogs), filled with PPODA-QT after placement of a “framing” platinum coil (coil + PPODA-QT, 3 dogs), or packed with platinum coils (coils only, 3 dogs). Aneurysm occlusion was angiographically monitored immediately and 6 months after embolization. After 6 months, the ostial regions of explanted aneurysms were assessed macroscopically and histologically. Results All aneurysms showed 100% angiographic occlusion at 6 months, but turbulent blood flow was observed in 1 coils-only sample. Ostial regions of explanted coils-only aneurysms showed neointimal tissue surrounding individual coils but no continuous tissue layer over the aneurysm neck. All PPODA-QT aneurysms displayed smooth ostial surfaces, but 2 of 3 coil + PPODA-QT aneurysms showed polymer (unassociated with the coil) protruding into the vessel lumen, contributing to rough ostial surfaces. Neointimal tissue was present in PPODA-QT and coil + PPODA-QT aneurysms and covered smooth ostial surfaces more completely than in coils-only aneurysms. Conclusions This study compared neointimal tissue overgrowth in the ostium of experimental aneurysms embolized with PPODA-QT, PPODA-QT plus a framing coil, or coils alone. The coils-only and coil + PPODA-QT groups showed rough and discontinuous ostial surfaces, which hindered neointimal tissue coverage. The PPODA-QT aneurysms consistently produced smooth ostial surfaces that facilitated more complete neointimal tissue coverage over aneurysm necks.

Polymeric materials for embolic and chemoembolic applications

“…Proof of concept was confirmed in vivo using a canine model with surgically induced aneurysms in the lateral wall of the carotid artery [130]. PPODA and QT were combined in a 2:1 molar ratio to create a hydrophobic monomer solution.…”

Pulsatile Flow-Induced Fatigue-Resistant Photopolymerizable Hydrogels for the Treatment of Intracranial Aneurysms

“…In the past decade, various alternative embolic agents with improved packing density including hydrogel-coated coils (Taschner et al, 2018), shape memory polymer foams (Rodriguez et al, 2012;Horn et al, 2017) and in situ forming hydrogels have been reported (Takao et al, 2006;Barnett et al, 2009;Ishikawa et al, 2012;Bearat et al, 2013;Brennecka et al, 2013;Brady et al, 2017). Photopolymerizable hydrogels provide better spatial and temporal control over curing compared to hydrogels responsive to chemical, temperature or pH stimuli (Corrigan et al, 2019) and allow to fill any shapes in situ.…”

Application of a rabbit-elastase aneurysm model for preliminary histology assessment of the PPODA-QT liquid embolic

“…Cerebral aneurysms are found in 45 million individuals worldwide, and approximately 30,000 patients in the United states suffer from subarachnoid hemorrhage annually. [ 6 ] Following several clinical trials demonstrating the benefits of coil embolization, endovascular techniques for aneurysm treatment have been increasingly applied to a wide array of both ruptured and unruptured aneurysms. For larger aneurysms and particularly those with wide-neck dome-to-neck ( d: n ) ratios, coil embolization still poses significant challenges.…”

“…In lieu of a porous network of coils or a metal mesh that only partially blocks flow in an aneurysm, PPODA-QT can completely fill the aneurysm volume with a mass that is both solid and stable. [ 6 ] PPODA-QT may confer improved delivery control, vessel protection, and reduced recanalization rates in larger aneurysms with medium- to wide-necks [ Figure 1 ]. [ 6 , 7 , 25 ]…”

“…[ 6 ] PPODA-QT may confer improved delivery control, vessel protection, and reduced recanalization rates in larger aneurysms with medium- to wide-necks [ Figure 1 ]. [ 6 , 7 , 25 ]…”