Mechanics of hydrogel-based bioprinting: From 3D to 4D

Bioprinting has emerged as a powerful technique with widespread applications in biomedical engineering and other fields. In bioprinting, programmable patterns are enabled by ejecting hydrogels with/without cells from the nozzle and eventually 3D complex constructs can be obtained in a layer-by-layer manner. Subsequently, the hydrogels are crosslinked into solid state by physical or chemical methods. Recently, 3D bioprinting has been extended to 4D bioprinting where "time" as the fourth dimension is incorporated. In 4D bioprinting, the printed bioconstructs can change their shapes or functionalities when imposing an external stimulus. For 3D/4D bioprinting, some physical phenomena (e.g., formation of droplets/filaments, droplets impact upon the substrate, self-deformation triggered by stimuli) are closely related to mechanics, which will affect the printing resolution and fidelity of printed bioconstructs. Besides, cells are sensitive to mechanical cues, i.e., the mechanical microenvironment that cells experience during and post printing has significant effects on cells behaviors and functionalities. Understanding the mechanics in bioprinting is thus of great importance. In this paper, we summarize the physics of bioprinting from the viewpoint of solid and fluid mechanics. Lights are shed on the droplets/filaments formation, droplets impact upon the receiving surface, and the mechanical microenvironment that cells experience during and post printing. By analyzing the mechanics of bioprinting, this review could be of help in understanding the bioprinting mechanism and predicting the future direction.