Toward next-generation bioinks: Tuning material properties pre- and post-printing to optimize cell viability
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Introduction A subset of three-dimensional (3D) biomaterial printing is 3D printing of biomaterials containing cells (cell-laden), called bioinks. Bioprinting is an approach to on-demand 3D placement of cells that provides the means to create complex structures. Although there are many challenges, the most pressing is maintaining cell viability pre-, during, and post-3D printing. This article discusses those challenges along with what has been reported thus far with regard to preliminary relationships between bioink material properties and cells.
Current 3D bioprinting strategies This article is entirely focused on extrusion (filament)-based 3D printing, which is the most widely used and versatile additive manufacturing platform for printing a variety of inks, including those with higher viscosities.1 For extrusion-based 3D printing, ink “printability” can have different definitions depending on the approach and end goals. Liquid bioinks of varying viscosities can be printed onto a stage and subsequently exposed to a stimulus that induces gelation (Figure 1). This stimulus can be in the form of light (i.e., ultraviolet [UV] cross-linking), heat (thermal physical cross-linking), or cross-linker baths or mists (i.e., ionic cross-linking). In the case of liquid bioinks with gelation on-stage, the kinetics of cross-linking and the transition from sol to gel must be rapid
enough to prevent substantial spreading and collapse of the extruded bioink. The stimulus must be presented either immediately when the ink exits the nozzle or after completion of a single printed layer (layer-by-layer cross-linking). Alternatively, viscous (honey-like) liquid-phase bioinks or even weak gel-phase bioinks can be printed. The gel-phase inks provide enhanced structure fidelity over less viscous (viscosity close to that of water) liquid-phase inks. If crosslinking is not conducted layer-by-layer, it can be introduced all at once to the printed structure as a post-printing processing step. The viscosity of liquid-phase bioinks can be tuned by adding an inherently viscous substance, such as hyaluronic acid, or increasing the polymer fraction. For gel-phase inks, the mechanical properties can be tuned by changing the polymer fraction, polymer properties, or degree of cross-linking (Figure 1). One disadvantage of liquid-phase bioinks is cell sedimentation in the ink during 3D printing and the resulting inhomogeneity in the 3D printed structures. Gel-phase inks have been shown to overcome this challenge by “locking” cells in place by the rapid increase in pre-gel viscosity that occurs upon synthesis and the quick gelation that follows.2,3 The use of sacrificial materials in the 3D bioprinting process has emerged in several strategies: (1) co-printing a bioink with a sacrificial ink; (2) a sacrificial material shell printed around the bioink filament; (3) a sacrificial material additive
Alexandra L. Rutz, École des Mines de Saint-Étienne, France; [email protected] Phillip L. Lewis, Simpson Querrey Institute, Northwestern University, USA; phil
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