Predicting cell stress and strain during extrusion bioprinting

TL;DR

This paper combines simulations and experiments to analyze cell deformation during extrusion bioprinting, focusing on stresses at the nozzle exit, and develops methods to predict cell stress and strain based on printing parameters.

Contribution

It introduces novel simulation-based insights into cell deformation at the nozzle exit and provides simple predictive methods using only printing parameters.

Findings

Extensional stresses are significant for cells in the center of the nozzle.

Cell deformation is dominated by shear flow for off-center cells.

Predictive methods accurately estimate maximum cell stress and strain.

Abstract

Bioprinting of living cells can cause major shape deformations, which may severely affect cell survival and functionality. While the shear stresses occurring during cell flow through the printer nozzle have been quantified to some extent, the extensional stresses occurring as cells leave the nozzle into the free printing strand have been mostly ignored. Here we use Lattice-Boltzmann simulations together with a finite-element based cell model to study cell deformation at the nozzle exit. Our simulation results are in good qualitative agreement with experimental microscopy images. We show that for cells flowing in the center of the nozzle extensional stresses can be significant, while for cells flowing off-center their deformation is dominated by the shear flow inside the nozzle. From the results of these simulations, we develop two simple methods that only require the printing parameters (nozzle diameter, flow rate, bioink rheology) to (i) accurately predict the maximum cell stress occurring during the 3D bioprinting process and (ii) approximately predict the cell strains caused by the elongational flow at the nozzle exit.