Laboratory of Biological Structure Mechanics (LaBS), Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Milan, Italy.
Laboratory of Biological Structure Mechanics (LaBS), Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Milan, Italy; Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zürich, Switzerland.
Comput Biol Med. 2022 Aug;147:105753. doi: 10.1016/j.compbiomed.2022.105753. Epub 2022 Jun 17.
Restenosis following percutaneous transluminal angioplasty (PTA) in femoral arteries is a major cause of failure of the revascularization procedure. The arterial wall response to PTA is driven by multifactorial, multiscale processes, whose complete understanding is lacking. Multiscale agent-based modeling frameworks, simulating the network of mechanobiological events at cell-tissue scale, can contribute to decipher the pathological pathways of restenosis. In this context, the present study proposes a fully-automated multiscale agent-based modeling framework simulating the arterial wall remodeling due to the wall damage provoked by PTA and to the altered hemodynamics in the post-operative months.
The framework, applied to an idealized femoral artery model, integrated: (i) a PTA module (i.e., structural mechanics simulation), computing the post-PTA arterial morphology and the PTA-induced damage (ii) a hemodynamics module (i.e., computational fluid dynamics simulations), quantifying the near-wall hemodynamics, and (iii) a tissue remodeling module simulating cellular activities through an agent-based model.
The framework was able to capture relevant features of the 3-month arterial wall response to PTA, namely (i) the impact of the PTA-induced damage and altered hemodynamics on arterial wall remodeling, including the local intimal growth at the most susceptible regions (i.e., elevated damage levels and low wall shear stress), (ii) the lumen area temporal trend resulting from the interaction of the two inputs, and (iii) a 3-month lumen area restenosis of ∼25%, in accordance with clinical evidence.
The overall results demonstrated the framework potentiality in capturing mechanobiological processes underlying restenosis, thus fostering future application to patient-specific scenarios.
经皮腔内血管成形术（PTA）后股动脉再狭窄是血运重建失败的主要原因。PTA 后动脉壁的反应是由多因素、多尺度过程驱动的，目前对此还缺乏全面的了解。多尺度基于代理的建模框架可以模拟细胞-组织尺度上的力学-生物学事件网络，有助于阐明再狭窄的病理途径。在这种情况下，本研究提出了一种全自动多尺度基于代理的建模框架，模拟了 PTA 引起的血管壁损伤和术后数月血流动力学改变导致的动脉壁重构。
该框架应用于理想化的股动脉模型，集成了：（i）PTA 模块（即结构力学模拟），计算 PTA 后动脉形态和 PTA 引起的损伤；（ii）血流动力学模块（即计算流体动力学模拟），量化近壁血流动力学；（iii）组织重构模块，通过基于代理的模型模拟细胞活动。
该框架能够捕捉到 PTA 后 3 个月动脉壁反应的相关特征，包括：（i）PTA 引起的损伤和血流动力学改变对动脉壁重构的影响，包括最易受影响区域的局部内膜增生（即损伤水平高和壁切应力低）；（ii）两种输入相互作用导致的管腔面积时间趋势；（iii）与临床证据一致的 3 个月管腔面积再狭窄约 25%。
总体结果表明该框架在捕捉再狭窄相关的力学-生物学过程方面具有潜力，从而促进了未来在患者特定情况下的应用。
