Development of Patient-Specific Shape Memory Polymer Foams for the Treatment of Intracranial Aneurysms

Abstract

The objectives of this research include: (1) designing an electrically conductive shape memory polymer (SMP) material, (2) developing a method for the systematic fabrication of SMPs with complex three-dimensional geometries based on computerized angiography tomography (CTA) of human patients, and (3) establishing translation strategies for a SMP-based endovascular device for the treatment of unruptured saccular intracranial aneurysms (ICA). We first characterized the thermomechanical properties of a porous polyurethane SMP that was infiltrated with carbon nanotubes (CNT) to induce electric conductivity in the polymeric matrix. The CNT-infiltrated SMP foams were characterized using materials science techniques that include: (i) differential scanning calorimetry (DSC) to determine the effect of CNT-infiltration on the thermal properties of the material; (ii) scanning electron microscopy (SEM) to characterize the pore morphology and interconnectivity, and (iii) uniaxial compressive testing, to characterize the effect of CNT-infiltration in the cyclic mechanical properties of the material. Then, we demonstrated the use of a CNT-infiltrated SMP foam to occlude an idealized aneurysm phantom. From these experiments, we determined that CNT-infiltrated SMP materials have the potential to be used as ICA embolic devices. However, these materials were subject to several limitations that make their translation difficult, including poor mechanical properties under cyclic compression, and a relatively high electric resistivity, that requires high currents to trigger shape recovery of the SMP. Based on the observed limitations of the CNT-infiltrated SMP material, we further performed two studies to improve the performance of our polyurethane formulation to be used as an embolic device for ICA endovascular therapy. First, we developed a method for the manufacturing of SMPs with complex 3D geometries. Due to the high degree of chemical crosslinking present in our SMP formulation, traditional 3D-printing techniques are not compatible with our material. Therefore, we developed a technique that combines leaching and 3D-printing for the fabrication of SMP foams based on CTA-informed ICA geometries. First, we fabricated polyvinyl alcohol (PVA) templates with custom pore geometries and densities. Then, we used these templates to fabricate our SMP material. By means of washing out the PVA after SMP curing, we obtained 3DSMP foams that mimicked the PVA template geometry. We also explored the effect of PVA leaching on the thermomechanical properties of the material. We found, from DSC, that the PVA leaching process induced a reduction in the glass transition temperature of the material (T_g), due to the chemical modification of the urethane groups. In addition, we found that the 3DSMP foams exhibited anisotropic mechanical properties and long-term shape recovery storage. Finally, we demonstrated the use of this manufacturing process to synthesize patient-specific 3DSMP foams. Using in vitro aneurysm models, we demonstrated that these personalized foams had the potential to provide complete ICA occlusion immediately after treatment. Building on our knowledge on the fabrication of 3DSMP foams using a leaching/3D-printing method, we aimed to induce conductivity on the 3D matrices. To do this, we performed in situ polymerization of polypyrrole (PPy), a well-described biocompatible conductive polymer, on the surface of the foams. We also modified our leaching/3D-printing method to prevent the reduction of the T_g of the material. The coating of the 3DSMP foam resulted in the induction of excellent electric conductivity on the polyurethane material. We observed that the material exhibited significantly lower resistivities than the previously developed CNT-infiltrated SMPs. This allowed the 3DSMP foams to undergo the Joule-heating process at low voltages and reach temperatures above T_g in less than 10 seconds. In addition, we developed a system to control the maximum temperature reached by the foams using pulsed electrical signals. Further, the PPy-coated 3DSMP foams underwent recovery behaviors as a response to electric stimuli. These characterizations showed the potential of the PPy-coated 3DSMP material for the development of a novel endovascular device for the treatment of unruptured saccular ICAs. In addition to the development of the material properties and functionality as an endovascular device, we also focused on planning translational research that facilitates the application of the proposed SMP-based endovascular device in the clinic. To achieve this, we first established an animal model for the testing of our embolic device in vivo prior to clinical trial studies. This animal model involves the creation of saccular aneurysms in New Zealand rabbits. Aneurysms were surgically created at the right common carotid artery by temporarily ligating the artery and then allowing an elastase solution to degrade the elastic lamina of the vascular wall. This weakening of the wall induced the bulging of the artery. In this work, we explored the stability of the aneurysms at different periods and assessed the histological structure of the aneurysms. This animal model will serve as a means to test the in vivo biocompatibility and endovascular occlusion effectiveness of our PPy-coated 3DSMP foam in the future. These future studies will be comparing the immediate and long-term occlusion effectiveness between our SMP-based device and a “gold standard” device that is currently available in the market. This comparison will demonstrate the potential superior effectiveness of our individualized treatment approach. However, selecting the gold standard as the control group is a challenging decision, due to the great diversity of modern endovascular devices for the treatment of unruptured saccular ICAs. Therefore, we performed a first-of-its-kind meta-analysis of the immediate (day 0) and long-term (post-implantation)occlusion effectiveness of modern endovascular devices. We thus performed a systematic search of studies that characterized the complete occlusion degree of ICAs of endovascular devices. Our results suggested that the most prominent endovascular devices of modern times (Guglielmi detachable coils (GDCs), flow diverters and the Woven EndoBridge) exhibit similar long-term efficacy in ICA treatment. In addition, we further showed that the immediate occlusion probability of the GDCs is the highest among the compared devices. Therefore, we selected coiling techniques as the gold standard for the in vivo assessment of endovascular embolization efficacy of our SMP-based device.