Tissue-engineered vascular grafts hold great promise in many clinical applications, especially in pediatrics wherein growth potential is critical. A continuing challenge, however, is identification of optimal scaffold parameters for promoting favorable neovessel development. In particular, given the countless design parameters available, including those related to polymeric microstructure, material behavior, and degradation kinetics, the number of possible scaffold designs is almost limitless. Advances in computationally modeling the growth and remodeling of native blood vessels suggest that similar simulations could help reduce the search space for candidate scaffold designs in tissue engineering. In this study, we meld a computational model of in vivo neovessel formation with a surrogate management framework to identify optimal scaffold designs for use in the extracardiac Fontan circulation while comparing the utility of different objective functions. We show that evolving luminal radius and graft compliance can be matched to that of the native vein by the end of the simulation period with judicious combinations of scaffold parameters, although the inability to match these metrics at all times reveals constraints engendered by current materials. We emphasize further that there is yet a need to examine additional metrics, and combinations thereof, when seeking to optimize functionality and reduce the potential for adverse outcomes. Impact Statement Tissue-engineered vascular grafts have considerable promise for treating myriad conditions, and multiple designs are now in FDA-approved trials. Nevertheless, the search continues for the optimal design of the underlying polymeric scaffold. We present a novel melding of a computational model of vascular adaptation and a formal method of optimization that can aid in identifying optimal design parameters, with potential to save development time and costs while improving clinical outcomes.

中文翻译：

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使用计算建模优化组织工程血管移植设计。

组织工程化的血管移植物在许多临床应用中都具有广阔的前景，尤其是在增长潜力至关重要的儿科患者中。然而，持续的挑战是鉴定用于促进有利的新血管发育的最佳支架参数。特别是，考虑到可用的设计参数不计其数，包括与聚合物微结构，材料性能和降解动力学有关的设计参数，可能的支架设计数量几乎是无限的。在计算建模中天然血管的生长和重塑方面的进展表明，类似的仿真可以帮助减少组织工程中候选支架设计的搜索空间。在这个研究中，我们将一个体内新血管形成的计算模型与一个替代管理框架相结合，以识别用于心外Fontan循环的最佳支架设计，同时比较不同目标功能的效用。我们显示，随着支架参数的明智组合，在模拟期结束时，不断变化的管腔半径和移植物顺应性可以与天然静脉相匹配，尽管无法始终匹配这些指标揭示了当前材料所带来的限制。我们进一步强调，在寻求优化功能并减少潜在不良后果时，还需要检查其他指标及其组合。影响陈述组织工程化的血管移植物有望治疗多种疾病，现在，多种设计正在FDA批准的试验中。尽管如此，仍在寻找基础聚合物支架的最佳设计。我们提出了一种新型的血管适应性计算模型融合方法和一种正式的优化方法，可以帮助确定最佳设计参数，并有可能节省开发时间和成本，同时改善临床结果。