Abstract
Hydrogels are widely used in the development of bioinks for extrusion-based 3D bioprinting (EBB). The rheological properties of these materials have already been studied extensively in the literature, and characteristics such as shear-thinning, yield stress and quick structural recovery upon flow cessation are deemed key properties to obtain bioinks of superior performance in EBB. However, there are still inconsistencies in the usage of shear rheology for the characterization of hydrogels for EBB. Therefore, this review discusses the rheometrical techniques applied to the development and characterization of inks for extrusion-based 3D bioprinting. More specifically, the focus will be on the applicability of shear rheometry in EBB as well as important underlying rheological concepts. Rheological tests were categorized according to the nature of the applied stimuli during rheometrical testing, e.g., continuous or oscillatory shear rheometry. In the first class of tests, the flow curves and the shear-thinning behaviour of Power-law fluids are tackled, and the relevance of this effect is discussed in the context of EBB and cell viability. The importance of rapid structural recovery of the material after shear-thinning is illustrated with examples. Then, the Herschel-Bulkley model for yield stress fluids and their connection with improved shape fidelity is highlighted. Oscillatory tests, such as amplitude-, frequency-, temperature- and time-sweeps, and their most relevant applications in EBB, such as gel strength and flowability, gel/liquid-like states, transition temperatures and processing temperatures, and equilibrium modulus after crosslinking are closely reviewed. In addition, relationships between rheological testing and the determination of process parameters are given in a section dedicated to the flow characteristics in EBB. Finally, we offer some future directions for rheology of EBB inks, aiming at the conception of next-generation bioinks.
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