Strain softening and hysteresis arising from 3D multicellular dynamics during long-term large deformation

IF 3.3 2区医学 Q2 ENGINEERING, BIOMEDICAL

Journal of the Mechanical Behavior of Biomedical Materials Pub Date : 2025-04-05 DOI:10.1016/j.jmbbm.2025.107001

Ken-ichi Tsubota , Shota Horikoshi , Tetsuya Hiraiwa , Satoru Okuda

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Abstract

Living tissues exhibit complex mechanical properties, including viscoelastic and elastoplastic responses, that are crucial for regulating cell behaviors and tissue deformations. Despite their significance, the intricate properties of three-dimensional (3D) cell constructs are not well understood and are inadequately implemented in biomaterial engineering. To address this gap, we developed a numerical method to analyze the dynamic properties of cell constructs using a 3D vertex model framework. By focusing on 3D tissues composed of confluent homogeneous cells, we characterized their properties in response to various deformation magnitudes and time scales. Stress relaxation tests revealed that large deformations initially induced relaxation in the shapes of individual cells. This process is amplified by subsequent transient cell rearrangements, homogenizing cell shapes and leading to tissue fluidization. Additionally, dynamic viscoelastic analyses showed that tissues exhibited strain softening and hysteresis during large deformations. Interestingly, this strain softening originates from multicellular structures independent of cell rearrangement, while hysteresis arises from cell rearrangement. Moreover, tissues exhibit elastoplastic responses over the long term, which are well represented by the Ramberg–Osgood model. These findings highlight the characteristic properties of cell constructs emerging from their structures and rearrangements, especially during long-term large deformations. The developed method offers a new approach to uncover the dynamic nature of 3D tissue mechanics and could serve as a technical foundation for exploring tissue mechanics and advancing biomaterial engineering.

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长期大变形过程中三维多胞动力学引起的应变软化和迟滞现象

活体组织表现出复杂的力学特性，包括粘弹性和弹塑性反应，这对调节细胞行为和组织变形至关重要。尽管它们具有重要意义，但三维（3D）细胞结构的复杂特性尚未得到很好的理解，并且在生物材料工程中没有充分实现。为了解决这一差距，我们开发了一种数值方法来分析使用三维顶点模型框架的细胞结构的动态特性。通过聚焦由融合均匀细胞组成的三维组织，我们表征了它们在不同变形幅度和时间尺度下的特性。应力松弛试验表明，大变形最初引起单个细胞形状的松弛。这一过程被随后的短暂细胞重排、细胞形状均质化和导致组织流化放大。此外，动态粘弹性分析表明，在大变形过程中，组织表现出应变软化和滞后。有趣的是，这种应变软化源于独立于细胞重排的多细胞结构，而迟滞源于细胞重排。此外，组织在长期内表现出弹塑性反应，这在Ramberg-Osgood模型中得到了很好的体现。这些发现突出了细胞结构的特征，这些特征来自于它们的结构和重排，特别是在长期的大变形中。该方法为揭示三维组织力学的动态本质提供了一种新的途径，可以作为探索组织力学和推进生物材料工程的技术基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of the Mechanical Behavior of Biomedical Materials 工程技术-材料科学：生物材料

CiteScore

7.20

自引率

7.70%

发文量

505

审稿时长

46 days

期刊介绍： The Journal of the Mechanical Behavior of Biomedical Materials is concerned with the mechanical deformation, damage and failure under applied forces, of biological material (at the tissue, cellular and molecular levels) and of biomaterials, i.e. those materials which are designed to mimic or replace biological materials. The primary focus of the journal is the synthesis of materials science, biology, and medical and dental science. Reports of fundamental scientific investigations are welcome, as are articles concerned with the practical application of materials in medical devices. Both experimental and theoretical work is of interest; theoretical papers will normally include comparison of predictions with experimental data, though we recognize that this may not always be appropriate. The journal also publishes technical notes concerned with emerging experimental or theoretical techniques, letters to the editor and, by invitation, review articles and papers describing existing techniques for the benefit of an interdisciplinary readership.