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应用 3D 打印技术创建体外动脉瘤破裂模型。

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

机构信息

Department of Mechanical Engineering, Northern Arizona University, Flagstaff, Arizona, USA.

出版信息

J Biomed Mater Res B Appl Biomater. 2024 Aug;112(8):e35465. doi: 10.1002/jbm.b.35465.

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设备治疗的效果。具体来说,目前的模型不能代表巨型动脉瘤的机械不稳定性(定义为高度或宽度为 25 毫米的动脉瘤),也不能在模拟生理条件下可靠地破裂。因此,需要具有生物力学相关材料特性和可预测破裂时间框架的体外动脉瘤模型,以准确评估新的医疗器械治疗选择的效果。了解动脉瘤在接近破裂时的材料特性(例如,剪切和压缩模量)是创建与病理相关且复杂的体外动脉瘤破裂模型的关键步骤。我们通过酶处理来研究血管的材料特性变化,以模拟动脉瘤壁的降解,并使用最新的添加剂制造技术(3D 打印)和组织样材料来创建复杂的动脉瘤破裂模型。在 37°C 下孵育 30 分钟以模拟生化活性对接近破裂的动脉瘤壁的影响,评估猪颈动脉的机械性能(剪切和压缩模量)与对照血管(未经处理)相比。为了与这些动脉血管进行比较,测试了柔软灵活的 3D 打印材料(VCA-A30:30 肖氏 A 硬度)的机械强度。然后,将这种材料用于创建球形的、超大尺寸(直径 25 毫米)的动脉瘤模型,并在神经血管压力(120/80±5mmHg)、每分钟心跳数(BPM=70)和代表大脑中动脉的流量下运行[MCA:142.67(±20.13)mL/min]使用血液模拟物[3.6(±0.4)cP 粘度],具有非牛顿剪切稀化特性。猪颈动脉在治疗前的剪切模量为 12.2(±2.7)kPa,压缩模量为 663.5(±111.6)kPa。在用胶原酶 D 进行酶处理后,动物组织的剪切模量降低了 33%(p 值=0.039),而压缩模量保持统计学不变(p 值=0.615)。对照组(未经处理的血管)显示剪切模量减少 13%(p 值=0.226),压缩模量增加 78%(p 值=0.034)。3D 打印材料的剪切模量为 228.59(±24.82)kPa,压缩模量为 668.90(±13.16)kPa。该材料用于原型设计复杂的体外大型动脉瘤破裂模型。当承受生理压力和流速时,未经处理的模型始终在约 12 分钟时破裂。这些结果表明,利用最新的 3D 打印材料,在与生理相关的可编程泵连接的台式体外模型中,可以可靠地重现动脉瘤破裂。进一步的研究将调查在动脉瘤内不同的动脉瘤穹顶厚度区域的优化,具有可调的破裂时间,用于比较动脉瘤设备部署和基于动脉瘤模型内压力和流量变化的台式对照。这些优化的体外破裂模型最终可用于通过量化特定设备破裂时间和动脉瘤破裂位置来测试设备治疗选择和破裂风险的效果。

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