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.
摘要：
目前可用的台式(体外)动脉瘤模型不足以测试血管内装置治疗的功效。具体来说,目前的模型并不代表巨大动脉瘤（定义为高或宽25毫米的动脉瘤）的机械不稳定性，并且在模拟的生理条件下不能预测破裂。因此，需要具有生物力学相关材料特性和可预测破裂时间的体外动脉瘤模型,以准确评估新医疗设备治疗方案的疗效.了解动脉瘤的材料特性(例如，剪切和压缩模量）接近破裂是创建病理相关且复杂的体外动脉瘤破裂模型的关键一步。我们调查了血管物质特性的变化，通过酶处理，模拟动脉瘤壁的降解，并使用这些信息使用最新的增材制造技术（3D打印）与组织样材料创建复杂的动脉瘤破裂模型。在用胶原酶D酶孵育之前和之后(在37°C下30分钟)评估猪颈动脉血管的机械性质(剪切和压缩模量),以模拟与对照血管(未处理)相比生化活性对动脉瘤壁接近破裂的影响。测试了柔软且柔性的3D打印材料（VCA-A30:30肖氏A硬度）的机械强度，以与这些动脉血管进行比较。然后用这种材料制造球形，巨大大小（25毫米直径）的动脉瘤体模，并在神经血管压力（120/80±5mmHg）下运行，使用具有非牛顿剪切稀化特性的血液类似物[3.6（±0.4）cP粘度]，每分钟跳动（BPM=70）和代表大脑中动脉的流量[MCA：142.67（±20.13）mL/min]。治疗前猪颈动脉血管的剪切模量为12.2（±2.7）KPa，压缩模量为663.5（±111.6）KPa。经胶原酶D酶处理后，动物组织的剪切模量降低了33%(p值=.039),而压缩模量保持统计学不变(p值=.615)。对照组（未处理的血管）显示最小的减少（13％，剪切模量的p值=.226）和压缩模量的78％增加（p值=.034）。3D打印材料的剪切模量为228.59(±24.82)KPa,而其压缩模量为668.90(±13.16)KPa。该材料用于构建复杂的体外巨大动脉瘤破裂模型。当受到生理压力和流速时，未处理的模型在〜12分钟时始终破裂。这些结果表明，动脉瘤破裂可以在台式体外模型中一致地重建，利用最新的3D打印材料，连接到生理相关的可编程泵。进一步的研究将研究动脉瘤内各种动脉瘤圆顶厚度区域的优化，基于动脉瘤模型内压力和流量变化的可测量效应，可调整破裂时间，以比较动脉瘤装置的部署和台式控制。这些优化的体外破裂模型最终可用于通过量化特定的装置破裂时间和动脉瘤破裂位置来测试装置治疗选项和破裂风险的功效。
