RESUMEN
Extrusion-based bioprinting is an enabling biofabrication technique that is used to create heterogeneous tissue constructs according to patient-specific geometries and compositions. The optimization of bioinks as per requirements for specific tissue applications is an essential exercise in ensuring clinical translation of the bioprinting technologies. Most notably, optimum hydrogel polymer concentrations are required to ensure adequate mechanical properties of bioprinted constructs without causing significant shear stresses on cells. However, experimental iterations are often tedious for optimizing the bioink properties. In this work, a nonlinear finite element modeling approach has been undertaken to determine the effect of different bioink parameters such as composition, concentration on the range of stresses being experienced by the cells in the bioprinted construct. The stress distribution of the cells at different parts of the constructs has also been modeled. It is found that both bioink chemical compositions and concentrations can substantially alter the stress effects experienced by the cells. Concentrated regions of softer cells near pore regions were found to increase stress concentrations by almost three times compared with stress generated in cells away from the pores. The study provides a method for rapid optimization of bioinks, design of bioprinted constructs, as well as toolpath plans for fabricating constructs with homogenous properties.
RESUMEN
The response of cytoskeleton to mechanical cues plays a pivotal role in understanding several aspects of cellular growth, migration, and cell-cell and cell-matrix interactions under normal and diseased conditions. Finite element analysis (FEA) has become a powerful computational technique to study the response of cytoskeleton in the maintenance of overall cellular mechanics. With the revelation of role of external mechanical microenvironment on cell mechanics, FEA models have also been developed to simulate the effect of substrate stiffness on the mechanical properties of cancer cells. However, the models developed so far model cellular response under static mode, whereas in physiological condition, cells always experience dynamic loading conditions. To develop a more accurate model of cell-extracellular matrix (ECM) interactions, this paper models the cytoskeleton and other parts of the cell by beam and solid elements respectively, assuming spherical morphology of the cell. The stiffness and roughness of extracellular matrix were varied. Furthermore, static and dynamic sinusoidal loads were applied through a flat plate indenter on the cell along with providing sinusoidal strain at the substrate. It is observed that due to axial loading, cell reaches a plastic region, and when the sinusoidal loading is added to the axial load, the cell experiences permanent deformation. Degradation of the cytoskeleton elements and a physiologically more relevant spherical cap shape of the cell were also considered during the analysis. This study suggests that asperity topology of the substrate and indirect cyclic load can play a significant role in the shape alterations and motion of a cell.