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

Abstract

An alternative intracranial aneurysm embolic agent is emerging in the form of hydrogels due to their ability to be injected in liquid phase and solidify in situ. Hydrogels have the ability to fill an aneurysm sac more completely compared to solid implants such as those used in coil embolization. Recently, the feasibility to implement photopolymerizable poly(ethylene glycol) dimethacrylate (PEGDMA) hydrogels in vitro has been demonstrated for aneurysm application. Nonetheless, the physical and mechanical properties of such hydrogels require further characterization to evaluate their long-term integrity and stability to avoid implant compaction and aneurysm recurrence over time. To that end, molecular weight and polymer content of the hydrogels were tuned to match the elastic modulus and compliance of aneurysmal tissue while minimizing the swelling volume and pressure. The hydrogel precursor was injected and photopolymerized in an in vitro aneurysm model, designed by casting polydimethylsiloxane (PDMS) around 3D printed water-soluble sacrificial molds. The hydrogels were then exposed to a fatigue test under physiological pulsatile flow, inducing a combination of circumferential and shear stresses. The hydrogels withstood 5.5 million cycles and no significant weight loss of the implant was observed nor did the polymerized hydrogel protrude or migrate into the parent artery. Slight surface erosion defects of 2-10 μm in depth were observed after loading compared to 2 μm maximum for non-loaded hydrogels. These results show that our fine-tuned photopolymerized hydrogel is expected to withstand the physiological conditions of an in vivo implant study.

Keywords: erosion; fatigue; hydrogels; intracranial aneurysms; polyethylene glycol dimethacrylate; pulsatile fluid flow-induced loading.

Figure 1

(A) Proposed solution of using in situ photopolymerized hydrogel for intracranial aneurysm embolization instead of coil embolization. (B) Requirements and (C) Potential risks to be evaluated of such a solution.

Figure 2

Different steps of the in vitro intracranial aneurysm model fabrication.

Figure 3

(A) Volume swelling ratio in free and constrained (within the aneurysm model) conditions, revealing a significant increase of the volume swelling ratio when increasing PEGDMA molecular weight. Statistically significant differences are only displayed between the free and constrained swelling conditions. (B) Compressive elastic modulus of the hydrogels demonstrating higher elastic modulus for PEGDMA6k-10 compared to 2–20 kDa hydrogels. (C) Direct visualization of the hydrogels within the intracranial aneurysm model after 1 week of fluid flow-induced loading showing slight shrinkage of the PEGDMA2k-10 hydrogel at the neck and excessive protrusion of the PEGDMA20k-10 hydrogel. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 4

(A) Volume swelling ratio in free and constrained (within the aneurysm model) swelling conditions, showing a significant increase of the volume swelling ratio when increasing PEGDMA concentration. Statistically significant differences are only displayed between the free and constrained swelling conditions. (B) Maximal pressure induced by the swollen hydrogels increases when increasing the polymer content. (C) Strain-stress curve of the compression test, revealing a significant increase of the elastic modulus with the polymer content. (D) Compliance of the hydrogels under physiological pressures (80–120 mmHg). Box plots depicted mean (white line) and values at 80 and 120 mmHg (bottom and top of the box). PEGDMA6k-10 and PEGDMA6k-15 hydrogels have a significant higher compliance than PEGDMA6k-20 hydrogels. * parent artery tissue data from literature (Ebrahimi, ; Ciszek et al., ; van Haaften et al., 2017). *p < 0.05, ***p < 0.001.

Figure 5

(A) Direct visualization of the hydrogels within the intracranial aneurysm model during 1 month of pulsatile fluid flow-induced loading showing complete occlusion without protrusion, migration, geometric distorsion nor signs of macroscopic damage. (B) Weight and (C) Mechanical property variations, normalized to the as-prepared state of the hydrogel, after 1 month of swelling and 1 month of fluid flow-induced loading. (D) Magnified microscopic view showing the surface profile of hydrogels in the as-prepared state (left), after 1 month of swelling (middle) and 1 month of fluid flow-induced loading (right), the latter revealing defects in the range of 2–10 μm in depth. *p < 0.05.