Cell viability in extrusion bioprinting: the impact of process parameters, bioink rheology, and cell mechanics

Abstract Extrusion bioprinting is a rapidly developing technology that prints cell-laden materials or “bioinks” to create complex, three-dimensional tissue constructs. This technology could play a key role in tissue engineering, drug screening, and cancer research. However, cells can be damaged or killed by extrusion forces during printing, limiting throughput and feature resolution. Here, we propose a critical strain-based cell model for predicting cell viability during extrusion that incorporates process parameters, bioink rheology, and cell mechanical properties. We extract parameters from practical nozzle diameters and extrusion flow rates, from power law and Herschel-Bulkley fits to bioink bulk rheology, and from single-cell rheology measurements of cell stiffness and fluidity, and then combine them for the first time to predict viability. This model agrees well with existing cell viability studies and further predicts that cell viability decreases with increasing flow rate, increasing bioink viscosity, increasing nozzle length, or decreasing nozzle radius. Mechanistically, these effects are linked to changes in shear stress or residence time of cells within the nozzle, where the properties of specific cell types dictate their deformation and ultimately damage. This work demonstrates that incorporating cell mechanical properties into cell viability models can improve the qualitative agreement between modeling and experiments and thus provide data-driven guidelines for bioprinting design optimization. Graphical abstract Strong extrusion stresses can impact cell health. Depending on the proccess parameters, bioink rheology, and cell properties, cells can be critically deformed during extrusion bioprinting, resulting in cell death. Damaged cells are predicted to be localized closer to the walls of the nozzle at a radial position r&gt; r $$_{c}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mmultiscripts> <mml:mrow/> <mml:mi>c</mml:mi> <mml:mrow/> </mml:mmultiscripts> </mml:math> .