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Maintaining Functionality of Biological Materials during Fluid–based Manufacturing



Change log


Evans, Susannah 


Drop on demand inkjet printing and extrusion–based printing enable 2D and 3D structures to be produced with high spacial resolution, highly applicable for the pharmaceutical industry where constructs can be used for tissue engineering, drug discovery and drug delivery applications. However, both of these fluid– based manufacturing techniques impart extensive shear forces to the ink during processing. When inks contain functional materials such as proteins, these forces are reported to be large enough to disrupt the resulting structure and activity of the ink after printing. Yet the precise cause of this damage is poorly understood and factors such as adsorption and drying can be conflated with observations of activity loss. This research aims to build a better understanding of the impact inkjet printing and extrusion have on the ink and functional material being printed. For inkjet systems, the elements of the printing process, ink formulation, ancillary equipment, printhead choice, nozzle flow, droplet formation and drying are examined in isolation. Techniques that are more controlled than previously reported are used to determine protein activity losses for each element to assess the contribution from each stage of printing. With this knowledge, strategies to retain protein activity are then investigated, particularly focusing on ink formulation and the losses due to drying and adsorption. A similar approach is taken to examine the damage the extrusion process causes to collagen gels separating the manufacture of the gel and its subsequent processing. Overall, this work has determined for the enzyme systems studied, adsorption and drying are the reasons inkjet printed enzymes have been observed to lose activity through separating out and controlling each element of the inkjet printing process. Methods to print without activity losses have been achieved through formulating inks with sugars and coating printheads with a sacrificial protein to prevent adsorption. A quality control technique using piezo axial vibration rheometry has also been validated for extrusion–based printing, to assess the damage to hydrogel–based inks during manufacture and printing, demonstrated with collagen gels. The forces endured during extrusion have also been mapped out with a simulation. These results pave the way forward for more extensive industrial adoption of inkjet and extrusion–based printing.





Daly, Ronan


inkjet, bioprinting, extrusion


Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge
EPSRC (1829861)