Multiscale mechanical characterization and computational modeling of fibrin gels
Multiscale mechanical characterization and computational modeling of fibrin gels
复制标题
纤维蛋白凝胶的多尺度力学表征和计算模型
DOI：
10.1016/j.actbio.2023.03.026
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发表时间：
2023
影响因子：
9.7
通讯作者：
Calve, Sarah
中科院分区：
文献类型：
--
作者：
Jimenez, Julian M.;Tuttle, Tyler;Guo, Yifan;Miles, Dalton;Buganza-Tepole, Adrian;Calve, Sarah
纤维蛋白是一种自然产生的蛋白质网络，在伤口愈合过程中形成一个临时结构，使重建成为可能。它也是一种常见的组织工程支架，因为它的结构特性可以控制。然而，为了充分表征伤口愈合过程并改进再生支架的设计，有必要在多个尺度上了解纤维蛋白力学。在这里，我们提出了一种在单向拉伸试验中量化宏观尺度（1-10 mm）应力应变响应和中尺度（10-1000µm）网络结构变形的策略。实验数据然后被用来告知计算模型，以准确地捕捉纤维蛋白凝胶的机械反应。荧光团共轭纤维蛋白凝胶的同时力学测试和共聚焦显微镜成像显示，变形凝胶的体积减少高达88%，同时体积分数增加，非仿射纤维在变形方向排列。计算模型与有限元分析相结合，使我们能够预测异质纤维蛋白凝胶中随材料性能空间变化的应变场。这些策略可以扩展到表征和预测其他异质生物组织和基质的宏观力学和中尺度网络组织。纤维蛋白是一种自然产生的支架，支持细胞生长和新组织的组装，具有可调的材料特性。表征纤维蛋白凝胶网络的中观和宏观力学可以促进对伤口愈合过程的理解，并影响未来的组织工程方法。利用纤维蛋白凝胶的结构和力学特性，建立了多尺度纤维蛋白网络力学预测的理论和计算模型。这些数据和模型可用于设计具有可调性能的凝胶。
Fibrin is a naturally occurring protein network that forms a temporary structure to enable remodeling during wound healing. It is also a common tissue engineering scaffold because the structural properties can be controlled. However, to fully characterize the wound healing process and improve the design of regenerative scaffolds, understanding fibrin mechanics at multiple scales is necessary. Here, we present a strategy to quantify both the macroscale (1–10 mm) stress-strain response and the deformation of the mesoscale (10–1000 µm) network structure during unidirectional tensile tests. The experimental data were then used to inform a computational model to accurately capture the mechanical response of fibrin gels. Simultaneous mechanical testing and confocal microscopy imaging of fluorophore-conjugated fibrin gels revealed up to an 88% decrease in volume coupled with increase in volume fraction in deformed gels, and non-affine fiber alignment in the direction of deformation. Combination of the computational model with finite element analysis enabled us to predict the strain fields that were observed experimentally within heterogenous fibrin gels with spatial variations in material properties. These strategies can be expanded to characterize and predict the macroscale mechanics and mesoscale network organization of other heterogeneous biological tissues and matrices.Statement of significanceFibrin is a naturally-occurring scaffold that supports cellular growth and assembly ofde novotissue and has tunable material properties. Characterization of meso- and macro-scale mechanics of fibrin gel networks can advance understanding of the wound healing process and impact future tissue engineering approaches. Using structural and mechanical characteristics of fibrin gels, a theoretical and computational model that can predict multiscale fibrin network mechanics was developed. These data and model can be used to design gels with tunable properties.