Department of Biomedical Engineering, Thoraxcenter Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Sci Rep. 2022 Mar 31;12(1):5434. doi: 10.1038/s41598-022-08425-4.
A significant amount of vascular thrombotic events are associated with rupture of the fibrous cap that overlie atherosclerotic plaques. Cap rupture is however difficult to predict due to the heterogenous composition of the plaque, unknown material properties, and the stochastic nature of the event. Here, we aim to create tissue engineered human fibrous cap models with a variable but controllable collagen composition, suitable for mechanical testing, to scrutinize the reciprocal relationships between composition and mechanical properties. Myofibroblasts were cultured in 1 × 1.5 cm-sized fibrin-based constrained gels for 21 days according to established (dynamic) culture protocols (i.e. static, intermittent or continuous loading) to vary collagen composition (e.g. amount, type and organization). At day 7, a soft 2 mm ∅ fibrin inclusion was introduced in the centre of each tissue to mimic the soft lipid core, simulating the heterogeneity of a plaque. Results demonstrate reproducible collagenous tissues, that mimic the bulk mechanical properties of human caps and vary in collagen composition due to the presence of a successfully integrated soft inclusion and the culture protocol applied. The models can be deployed to assess tissue mechanics, evolution and failure of fibrous caps or complex heterogeneous tissues in general.
大量血管血栓事件与覆盖动脉粥样硬化斑块的纤维帽破裂有关。然而，由于斑块的异质组成、未知的材料特性以及事件的随机性，纤维帽破裂很难预测。在这里，我们旨在创建具有可变性但可控胶原组成的组织工程化人纤维帽模型，适用于机械测试，以仔细研究组成和机械性能之间的相互关系。根据既定（动态）培养方案（即静态、间歇或连续加载），将成纤维细胞培养在 1×1.5 厘米大小的纤维蛋白约束凝胶中 21 天，以改变胶原组成（例如数量、类型和组织）。在第 7 天，在每个组织的中心引入一个柔软的 2 毫米∅纤维蛋白内含物，以模拟软脂核心，模拟斑块的异质性。结果表明，可复制的胶原组织，模拟了人帽的整体机械性能，并由于成功整合的软内含物和应用的培养方案而在胶原组成上有所不同。这些模型可用于评估纤维帽或一般复杂异质组织的组织力学、演变和失效。
