The
emergence of 3D bioprinting has allowed a variety of hydrogel-based
“bioinks” to be printed in the presence of cells to
create precisely defined cell-loaded 3D scaffolds in a single step
for advancing tissue engineering and/or regenerative medicine. While
existing bioinks based primarily on ionic cross-linking, photo-cross-linking,
or thermogelation have significantly advanced the field, they offer
technical limitations in terms of the mechanics, degradation rates,
and the cell viabilities achievable with the printed scaffolds, particularly
in terms of aiming to match the wide range of mechanics and cellular
microenvironments. Click chemistry offers an appealing solution to
this challenge given that proper selection of the chemistry can enable
precise tuning of both the gelation rate and the degradation rate,
both key to successful tissue regeneration; simultaneously, the often
bio-orthogonal nature of click chemistry is beneficial to maintain
high cell viabilities within the scaffolds. However, to date, relatively
few examples of 3D-printed click chemistry hydrogels have been reported,
mostly due to the technical challenges of controlling mixing during
the printing process to generate high-fidelity prints without clogging
the printer. This review aims to showcase existing cross-linking modalities,
characterize the advantages and disadvantages of different click chemistries
reported, highlight current examples of click chemistry hydrogel bioinks,
and discuss the design of mixing strategies to enable effective 3D
extrusion bioprinting of click hydrogels.