Over the past two decades, the increase in prevalence of cardiovascular diseases and the limited availability of autologous blood vessels and saphenous vein grafts have motivated the development of tissue-engineered vascular grafts (TEVGs). However, compliance mismatch and poor mechanical properties of the TEVGs remain as two major issues that need to be addressed. Researchers have investigated the role of various culture conditions and mechanical conditioning in deposition and orientation of collagen fibers, which are the key structural components in the vascular wall; however, the intrinsic complexity of mechanobiological interactions demands implementing new engineering approaches that allow researchers to investigate various scenarios more efficiently. In this study, we utilized a coupled agent-based finite element analysis (AB-FEA) modeling approach to study the effect of various loading modes (uniaxial, biaxial, and equibiaxial), boundary conditions, stretch magnitudes, and growth factor concentrations on growth and remodeling of smooth muscle cell-populated TEVGs, with specific focus on collagen deposition and orientation. Our simulations (12 weeks of culture) showed that biaxial cyclic loading (and not uniaxial or equibiaxial) leads to alignment of collagen fibers in the physiological directions. Moreover, axial boundary conditions of the TEVG act as determinants of fiber orientations. Decreasing the serum concentration, from 10% to 5% or 1%, significantly decreased the growth and remodeling speed, but only affected the fiber orientation in the 1% serum case. In conclusion, in silico tissue engineering has the potential to evolve the future of tissue engineering, as it will allow researchers to conceptualize various interactions and investigate numerous scenarios with great speed. In this study, we were able to predict the orientation of collagen fibers in TEVGs using a coupled AB-FEA model in less than 8 h. Impact Statement Tissue-engineered vascular grafts (TEVGs) hold potential to replace the current gold standard of vascular grafting, saphenous vein grafts. However, developing TEVGs that mimic the mechanical performance of the native tissue remains a challenging task. We developed a computational model of the grafts' remodeling processes and studied the effects of various loading mechanisms and culture conditions on collagen fiber orientation, which is a key factor in mechanical performance of the grafts. We were able to predict the fiber orientations accurately and show that biaxial loading and axial boundary conditions are important factors in collagen fiber organization.

中文翻译：

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在计算机组织工程中：基于耦合代理的有限元方法。

在过去的二十年中，心血管疾病的患病率增加，自体血管和大隐静脉移植物的供应有限，促使组织工程化血管移植物（TEVG）的发展。但是，TEVG的不匹配和机械性能差仍然是需要解决的两个主要问题。研究人员研究了各种培养条件和机械条件在胶原纤维沉积和定向中的作用，胶原纤维是血管壁的关键结构成分。然而，机械生物学相互作用的内在复杂性要求实施新的工程方法，使研究人员能够更有效地研究各种情况。在这个研究中，我们使用了基于耦合主体的有限元分析（AB-FEA）建模方法来研究各种加载模式（单轴，双轴和等双轴），边界条件，拉伸幅度和生长因子浓度对平滑生长和重构的影响肌细胞填充的TEVG，特别关注胶原蛋白的沉积和方向。我们的模拟（培养12周）显示，双轴循环载荷（而不是单轴或等双轴）导致胶原纤维在生理方向上对齐。此外，TEVG的轴向边界条件是纤维取向的决定因素。将血清浓度从10％降低至5％或1％，可显着降低生长和重塑速度，但仅在1％血清情况下影响纤维方向。结论，硅组织工程学领域的研究具有发展组织工程学未来的潜力，因为它将使研究人员能够概念化各种相互作用并快速研究众多场景。在这项研究中，我们能够使用耦合的AB-FEA模型在不到8小时的时间内预测TEVGs中胶原纤维的取向。影响力声明组织工程化的血管移植物（TEVG）有望取代目前的大隐静脉移植物金标准。但是，开发模仿天然组织机械性能的TEVG仍然是一项艰巨的任务。我们开发了移植物重塑过程的计算模型，并研究了各种加载机制和培养条件对胶原纤维取向的影响，这是移植物机械性能的关键因素。