Modelling cell deformations in bioprinting process using a multicompartment-smooth particle hydrodynamics approach

Abstract

Bioprinting using cell-laden bioink is a rapidly emerging additive manufacturing method to fabricate engineered tissue constructs and in vitro models of disease biology. Amongst different bioprinting modalities, extrusion-based bioprinting is the most conveniently adopted technique due to its affordability. Bioinks consisting of living cells are suspended in hydrogels and extruded through syringe-needle assemblies, which subsequently undergo gelation at the collector plate. During the process, pressure is exerted on living cells which may cause cell deaths. Thus, for selected combination of cell and hydrogel, exerted pressure and the extrusion play key roles in determining the cell viability. Experimental evaluation to characterise stresses experienced by the cells in a bioink during bioprinting is a tedious exercise. Herein, computational modelling can be applied efficiently for rapid screening of bioinks. In the present study, a smoothed particle hydrodynamics model is developed for the analysis of stresses exerted on the cells during bioprinting process. Cells are modelled by assigning different mechanical properties to nucleus, cytoskeleton and cell membrane regions of the cell to get a more realistic understanding of cell deformation. The cytoplasm and nucleus are modelled as finite element meshes and a spring model of the cell membrane is coupled to the finite element model to develop a three-compartment model of the cell. Cell deformation is taken as a potential indicator of cell death. Effect of different process parameters such as flow rate, syringe-nozzle geometry and cell density are investigated. A submodeling approach is further introduced to predict deformation with higher resolution in a unit volume containing 10⁴ to 10⁸ cells. Results suggest that the generated bioink flow dynamic model can be a useful tool for the computational study of fluid flow involving cell suspensions during a bioprinting process.