Cell-aware optimization of the extrusion-based bioprinting process

Extrusion-based bioprinting is currently one of the most used techniques to fabricate constructs for Tissue Engineering applications. When using bioinks (i.e., inks containing cells), the embedded cells may be damaged during extrusion mainly due to high shear stresses and/or the high exposure times to those stresses, posing a severe risk for the correct functionality of the final bioprinted product. The entity of this damage is strictly connected to the printing set-up (e.g., needle shape and internal diameter) and parameters chosen (e.g., printing speed, flowrate, layer height), which should be carefully tuned considering the trade-off with the printability requirements. In this context, we propose a novel mathematical model to predict cell damage during extrusion which integrates with an already existing one for printability assessment. The combined model can help predict a priori the outcome of a print, both in terms of cell viability and printability, and to fine-tune the printing parameters according to both constraints. The model equations were implemented in a web-page application (available at https://www.prin-vision.it/resources/), which can be used by the bioprinting community to optimize the printing process and thus speed-up the printing parameters selection process.