Pushing the rheological and mechanical boundaries of extrusion-based 3D bioprinting

Two bioprinting windows are defined based on the long-existing concept of biofabrication window to sufficiently describe the complete 3D bioprinting process, covering the structural printing and the subsequent biological cultivation. The poorly fulfilled requirement for super-soft bioprints (with modulus of the order of ≤1 kPa) that favor the culture of cells with a soft tissue origin has significantly driven the efforts on the expansion of bioprinting windows. Innovative crosslinking strategies have enabled the printing of liquid-like (or low-viscosity) bioinks, and the fabrication of innovative gel-phase formulations has advanced the bioprinting of solid-like bioinks. A fundamental principle for printing exceptionally soft hydrogels is to incorporate sacrificial materials, whereas printing stiff hydrogels mainly relies on the inclusion of mechanical reinforcers, both of which span from the mesoscale to the nanoscale range. Additional boundaries toward cell-rich bioinks and mechanically dynamic bioprints contribute toward the biomimicry of engineering functional tissues. 3D bioprinting has long been subjected to trade-offs between physicochemical and biological outcomes. The resulting material properties of the initial bioinks and final printing products usually lie within a moderate range, which limits the application of bioprinting and its products. Recent progress in bioinks and bioprinting techniques has significantly expanded the window of material properties. In this review, I define two bioprinting windows to clarify the trade-offs between physical chemistry and biology and provide a comprehensive overview of recent advances that have pushed the rheological boundaries of bioinks and mechanical boundaries of bioprints, focusing on unusual material properties. I illustrate this with recent examples, consolidate the existing strategies into well-defined categories, highlight the prominent trends, and provide perspectives on additional boundaries. 3D bioprinting has long been subjected to trade-offs between physicochemical and biological outcomes. The resulting material properties of the initial bioinks and final printing products usually lie within a moderate range, which limits the application of bioprinting and its products. Recent progress in bioinks and bioprinting techniques has significantly expanded the window of material properties. In this review, I define two bioprinting windows to clarify the trade-offs between physical chemistry and biology and provide a comprehensive overview of recent advances that have pushed the rheological boundaries of bioinks and mechanical boundaries of bioprints, focusing on unusual material properties. I illustrate this with recent examples, consolidate the existing strategies into well-defined categories, highlight the prominent trends, and provide perspectives on additional boundaries. the use of 3D printing technologies to fabricate biological models. a process used to create a 3D object by layering materials one by one based on a digital model; it is a terminology changeable with 3D printing. a formulation of cells that is suitable to be processed by an automated biofabrication technology. a process that generates a physical or chemical bond that links one polymer chain with another. ECM isolated from native tissues by chemically or physically removing the inhibiting cells. a hydrogel containing two types of networks with contrasting properties. a 3D network of extracellular macromolecules and minerals that provide structural and biochemical support to the surrounding cells. a type of bioprinting that applies an extrusion force to drive the flow of bioinks, which are expected to form filament-shaped building blocks for layered deposition. a 3D crosslinked network of hydrophilic polymers dissolved in water with the ability to hold a large amount of water. a fabrication technique derived from electrospinning that allows for the defined placing of microfibers. the ability of a bioink and the bioprinting process to deliver a structure based on a computer-aided design model. a branch of physics that studies the deformation and flow of matter, both solids and liquids. measure of a fluid’s resistance to deformation at a given shear rate. the stress corresponding to the yield point at which the material begins to deform plastically in response to an external force.