Application of 3D printing to create an in vitro aneurysm rupture model.

ABSTRACT

Currently available benchtop (in vitro) aneurysm models are inadequate for testing the efficacy of endovascular device treatments. Specifically, current models do not represent the mechanical instability of giant aneurysms (defined as aneurysms with 25 mm in height or width) and do not predictably rupture under simulated physiological conditions. Hence, in vitro aneurysm models with biomechanically relevant material properties and a predictable rupture timeframe are needed to accurately assess the efficacy of new medical device treatment options. Understanding the material properties of an aneurysm (e.g., shear and compression modulus) as it approaches rupture is a crucial step toward creating a pathologically relevant and sophisticated in vitro aneurysm rupture model. We investigated the change in material properties of a blood vessel, via enzymatic treatment, to simulate the degradation of an aneurysm wall and used this information to create a sophisticated aneurysm rupture model using the latest in additive manufacturing technologies (3D printing) with tissue-like materials. Mechanical properties (shear and compression modulus) of swine carotid vessels were evaluated before and after incubation with collagenase D enzyme (30 min at 37°C) to simulate the effect of biochemical activity on aneurysm wall approaching rupture compared to control vessels (untreated). Mechanical strength of a soft and flexible 3D-printed material (VCA-A30 30 shore A hardness) was tested for comparison to these arterial vessels. This material was then used to create spherical shaped, giant-sized (25-mm diameter) aneurysm phantoms and were run under neurovascular pressures (120/80 ± 5 mmHg), beats per minute (BPM = 70) and flows representing the middle cerebral artery [MCA 142.67 (±20.13) mL/min] using a blood analog [3.6 (±0.4) cP viscosity] with non-Newtonian shear-thinning properties. The shear modulus of swine carotid vessel before treatment was 12.2 (±2.7) KPa and compression modulus was 663.5 (±111.6) KPa. After enzymatic treatment by collagenase D, shear modulus of animal tissues reduced by 33% (p-value = .039) while compression modulus remained statistically unchanged (p-value = .615). Control group (untreated vessels) showed minimal reduction (13%, p-value = .226) in shear modulus and 78% increase (p-value = .034) in compression modulus. The shear modulus of the 3D-printed material was 228.59 (±24.82) KPa while its compression modulus was 668.90 (±13.16) KPa. This material was used to prototype a sophisticated in vitro giant aneurysm rupture model. When subjected to physiological pressures and flow rates, the untreated models consistently ruptured at ~12 min. These results indicate that aneurysm rupture can be recreated consistently in a benchtop in vitro model, utilizing the latest 3D-printed materials, connected to a physiologically relevant programmable pump. Further studies will investigate the optimization of various aneurysm dome thickness regions within the aneurysm, with tunable rupture times for comparison of aneurysm device deployment and benchtop controls based on the measurable effects of pressure and flow changes within the aneurysm models. These optimized in vitro rupture models could ultimately be used to test the efficacy of device treatment options and rupture risk by quantifying specific device rupture times and aneurysm rupture position.