Mechanical Considerations of Myocardial Tissue and Cardiac Regeneration

Jorba, Ignasi; Nikolić, Milena; Bouten, C.V.C.

doi:10.1007/978-3-031-23965-6_8

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“…The orientation and interaction of cells and extracellular matrix (ECM) components are strong determinants of biological tissue functionality [1,2]. In the heart, the anisotropy of the ECM present in the myocardial microenvironment is essential for coordinated cardiac contractions and force transmission through the multiple length scales of the myocardial tissue [3,4]. At the cellular level, the anisotropy is tightly linked to the orientation of cardiac fibroblasts (cFBs), which produce the ECM and mechanically remodel it via traction forces.…”

Section: Introductionmentioning

confidence: 99%

Steering cell orientation through light-based spatiotemporal modulation of the mechanical environment

Jorba,

Gussenhoven,

van der Pol

et al. 2024

Biofabrication

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The anisotropic organization of cells and the extracellular matrix (ECM) is essential for the physiological function of numerous biological tissues, including the myocardium. This organization changes gradually in space and time, during disease progression such as myocardial infarction. The role of mechanical stimuli has been demonstrated to be essential in obtaining, maintaining and de-railing this organization, but the underlying mechanisms are scarcely known. To enable the study of the mechanobiological mechanisms involved, in vitro techniques able to spatiotemporally control the multiscale tissue mechanical environment are thus necessary. Here, by using light-sensitive materials combined with light-illumination techniques, we fabricated 2D and 3D in vitro model systems exposing cells to multiscale, spatiotemporally resolved stiffness anisotropies. Specifically, spatial stiffness anisotropies spanning from micron-sized (cellular) to millimeter-sized (tissue) were achieved. Moreover, the light-sensitive materials allowed to introduce the stiffness anisotropies at defined timepoints (hours) after cell seeding, facilitating the study of their temporal effects on cell and tissue orientation. The systems were tested using cardiac fibroblasts (cFBs), which are known to be crucial for the remodeling of anisotropic cardiac tissue. We observed that 2D stiffness micropatterns induced cFBs anisotropic alignment, independent of the stimulus timing, but dependent on the micropattern spacing. cFBs exhibited organized alignment also in response to 3D stiffness macropatterns, dependent on the stimulus timing and temporally followed by (slower) ECM co-alignment. In conclusion, the developed model systems allow improved fundamental understanding on the underlying mechanobiological factors that steer cell and ECM orientation, such as stiffness guidance and boundary constraints.

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