Enhanced Piezoelectric Fibered Extracellular Matrix to Promote Cardiomyocyte Maturation and Tissue Formation: A 3D Computational Model

Abstract

Mechanical and electrical stimuli play a key role in tissue formation, guiding cell processes such as cell migration, differentiation, maturation, and apoptosis. Monitoring and controlling these stimuli on in vitro experiments is not straightforward due to the coupling of these different stimuli. In addition, active and reciprocal cell–cell and cell–extracellular matrix interactions are essential to be considered during formation of complex tissue such as myocardial tissue. In this sense, computational models can offer new perspectives and key information on the cell microenvironment. Thus, we present a new computational 3D model, based on the Finite Element Method, where a complex extracellular matrix with piezoelectric properties interacts with cardiac muscle cells during the first steps of tissue formation. This model includes collective behavior and cell processes such as cell migration, maturation, differentiation, proliferation, and apoptosis. The model has employed to study the initial stages of in vitro cardiac aggregate formation, considering cell–cell junctions, under different extracellular matrix configurations. Three different cases have been purposed to evaluate cell behavior in fibered, mechanically stimulated fibered, and mechanically stimulated piezoelectric fibered extra-cellular matrix. In this last case, the cells are guided by the coupling of mechanical and electrical stimuli. Accordingly, the obtained results show the formation of more elongated groups and enhancement in cell proliferation.

Computational modeling of multiple myeloma interactions with resident bone marrow cells

“…Our cell mechanical model assumes that cell internal deformations are a result of cell-cell and cell-ECM interactions [26]. The actin-myosin (AM) bundles, which are considered as a part of the cytoskeleton (CSK), are the main components that actively develop contractile forces within the cell, whereas other components of the CSK along with the cell membrane, act as resistive elements that oppose the cell internal deformation.…”

“…where 𝑡 is the cell-cycle progression time, and 𝑡 𝑚𝑎𝑡 is the time needed for the cell to complete the cell cycle [31]. The effects of the mechanical conditions, which can increase the rate of cell-cycle progression, are dependent on the cell's internal deformations [26]. So, the cell cycle time is dependent on the mechanical stimuli perceived by the cell at each time, 𝑡, which can be defined as:…”

“…Although they have been shown to be effective in the study of wound healing [18], bone remodeling [19], nutrient consumption for bioreactors design [20,21], and scaffolds design [22][23][24], these models do not recognize the individualized cell response, or the effects due to cellcell contacts and adhesion, which play a key role in tumor's growth and drug resistance development [11]. For their part, discrete models focus their study on the specific conditions of each individualized cell, being capable of reproducing cell-cell adhesions and the response they trigger [25][26][27]. In fact, different models are applied to the study of cell differentiation [28,29], proliferation [30][31][32], cell morphology [33][34][35][36], migration [25,[37][38][39], angiogenesis [27] and cell-level tissue architectures [30,31].…”

Stem Cell Studies in Cardiovascular Biology and Medicine: A Possible Key Role of Macrophages

“…Computation is a useful tool for regulating this parameter. Urdeitx and Doneider used a piezoelectric fibered extracellular matrix in a 3D computational model [ 87 ] to calculate the intracellular force affected by the fiber. Computational models can be powerful tools for estimating precise cellular changes that connect differentiation.…”

Impact of Electrospun Piezoelectric Core–Shell PVDFhfp/PDMS Mesh on Tenogenic and Inflammatory Gene Expression in Human Adipose-Derived Stem Cells: Comparison of Static Cultivation with Uniaxial Cyclic Tensile Stretching

“…Using this approach, cells seeded onto piezoelectric polymeric membranes undergo a double stimulation. The first stimulation regards the electric stimulation due to the piezoelectric effect of the material under dynamic loading, and the second concerns the physical stretching of the membrane [ 18 ]. The impact of mechanical stimulation on stem cells’ commitment is indeed well known [ 19 , 20 ].…”