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

Abstract

Background: PPODA-QT is a novel liquid embolic under development for the treatment of cerebral aneurysms. We sought to test the rabbit-elastase aneurysm model to evaluate the tissue response following PPODA-QT embolization. Methods: Experimental elastase-induced aneurysms were created in fourteen New Zealand White Rabbits. Eight animals were used for aneurysm model and endovascular embolization technique development. Six PPODA-QT-treated animals were enrolled in the study. Control and aneurysm tissues were harvested at acute (n = 2), 1-month (n = 2), and 3-month (n = 2) timepoints and the tissues were prepared for histology assessment. Results: All fourteen rabbit-elastase aneurysms resulted in small and medium aneurysm heights (<10 mm dome height) with highly variable neck morphologies, small midline dome diameters, and beyond-wide dome-to-neck (d: n) ratios. Histological evaluation of four aneurysms, treated with PPODA-QT, demonstrated reorganization of aneurysm wall elastin into a smooth muscle layer, and observed as early as the 1-month survival timepoint. At the aneurysm neck, a homogenous neointimal layer (200–300 μm) formed at the PPODA-QT interface, sealing off the parent vessel from the aneurysm dome. No adverse immune response was evident at 1- and 3-month survival timepoints. Conclusion: PPODA-QT successfully embolized the treated aneurysms. Following PPODA-QT embolization, neointimal tissue growth and remodeling were noted with minimal immunological response. The experimental aneurysms created in rabbits were uniformly small with inconsistent neck morphology. Further testing of PPODA-QT will be conducted in larger aneurysm models for device delivery optimization and aneurysm healing assessment before human clinical investigation.

Large, Wide‐Neck, Side‐Wall Aneurysm Treatment in Canines Using NeuroCURE: A Novel Liquid Embolic

“…The consistent large and wide-neck aneurysm size, morphology, and accessibility via a femoral puncture attained in the canine model proved to be much more relevant to the human condition than the rabbit aneurysm models treated with an early version of NeuroCURE in a previous study. 41 The canine aneurysms were all considered large on average when measured via angiography pre-embolization (11.27±1.77 mm maximal dome height). NeuroCURE fill volumes were also within 94.9%±2.3% of calculated aneurysm volumes ( Table 1 ).…”

Material characterization of GPX®: A versatile in situ solidifying embolic platform technology

“…One such system, referred to as PPODA-QT, comprises a solution of two hydrophobic monomers, poly (propylene glycol) diacrylate (PPODA) and pentaerythritol tetrakis (3-mercaptopropionate) (QT), which are crosslinked into a solid through Michael addition of the thiol groups to the acryloyl groups. Crosslinking is initiated when a high pH aqueous solution is emulsified into the solution of hydrophobic monomers immediately prior to injection through a microcatheter ( Riley et al, 2011 ; Huckleberry et al, 2021 ). Another two-component system, Embrace™, comprises a solution of polyethylene glycol (PEG) diacrylate monomers and a solution of an organic peroxide free radical initiator.…”