Effects of dispensing pressure and nozzle diameter on cell survival from solid freeform fabrication-based direct cell writing

Novel technologies are emerging that incorporate cells as part of the building blocks for various biomanufacturing processes, such as solid freeform fabricated tissue constructs for tissue regeneration, three-dimensional pharmacokinetic models, cell-based microelectromechanical systems, sensors, and microfluidic devices. However, the effects of these biomanufacturing processes on cells have not been fully studied. This paper examines the effect of solid freeform fabrication-based direct cell writing process, focusing on dispensing pressure and nozzle size, on the viability and functional behavior of HepG2 cells encapsulated within alginate. Our experimental results revealed a process-induced mechanical damage to cell membrane integrity, causing a quantifiable loss in cell viability due to incremental increases and decreases in the studied process parameters of dispensing pressure and nozzle size, respectively. The experimental results also suggested that cells may require a recovery period following direct cell writing biofabrication. The general finding of this study may be applicable to freeform fabrication of cell-based tissue constructs and three-dimensional biological models.