From rheological concepts to additive manufacturing assessment of hydrogel-based materials for advanced bioprinting applications

Hydrogels have emerged as highly attractive polymer-based materials owing to their unique solid–liquid rheological duality, which allows their use in 3D extrusion and inkjet printing, particularly in the field of biomedical applications. The dynamic moduli (storage modulus, G′, and loss modulus, G′′), relaxation modulus, shear-thinning behaviour, thixotropy, viscoelasticity, and yield stress are the most commonly employed rheological concepts for hydrogel applications in 3D/4D additive manufacturing. Extrusion, inkjet printing, and stereolithography are the most studied manufacturing technologies for hydrogel bioprinting applications. Moreover, hydrogels exhibit a combination of cohesive properties of solids and the transport characteristics of liquids. Their rheological behaviour, however, varies depending on whether they are chemically cross-linked, showing a pure solid elastic behaviour, or physically crosslinked, showing viscoelastic behaviour. While rheology reveals much information about the flow behaviour of liquids or deformation behaviour of solids, it is not as obvious as to anticipate the printability of hydrogels. Therefore, a deep understanding of rheological principles and their correlation with printability is essential. This review begins summarizing various polymer hydrogels. Subsequently, the definition and description of the most employed concepts, namely relaxation modulus, storage, and loss moduli, and many others, are necessary to understand and associate the feasibility of hydrogels for a particular bioprinting process. This review mainly addresses: (i) rheological determination of the processing window for direct ink writing (DIW), (ii) rheological restrictions for printing beyond direct ink writing (DIW), and (iii) vat photopolymerization bioprinting and the biological implications of bioprinting. Finally, all the above concepts are illustrated with a few examples of biomedical applications of 3D/4D printed hydrogels.