Smart Bioinks for bioengineering living tissues


Bioprinting is a promising technology to enable the design of more realistic tissue models. Since such printed models can be produced with patient-specific cells containing patient-specific genetic information they can provide a more accurate diagnostic tools to probe and monitor human pathobiology. If the printed materials are able to dynamically alter their properties over time to meet the changing needs of the embedded cells they will allow long-term cellular adaptation and tissue maturation, such as in a living tissue. To achieve such results, the use of smart bioink materials is essential.

Hydrogels are the gold-standard materials used as bioinks in bioprinting. They can beof natural or synthetic origin. Naturally-derived gels, such as collagen-based materials, are cell-compatible solutions often used for mimicking tissues containing collagen like cartilage, bone, skin etc. Fibrin-based gels have been extensively used for cardiovascular applications. Recombinant elastin-like gels have been employed for cartilage and neural tissue engineering. Interestingly, gels composed of synthetic polymers (e.g. PEG, PLA) or peptides have also been used to create engineered mimics of many of these same tissue types, despite their different structural and chemical properties, compared to natural gels.

Both classes of hydrogel have their own merits; however, when using bioprinting, you have to consider the chosen bioink material’s flow rheology, final matrix mechanics, and matrix biochemistry when selecting one to engineer advanced tissue models since the ability to optimise these material properties is what ultimately defines the potential applicability of each bioink.

Recently, researchers have turned to designing mixtures of natural and synthetic monomers, as well as functional additives to match the initial rheological, final mechanical, and biochemical demands of 3D bioprinting. However, it is not clear whether they allow long-term cellular adaptation and tissue maturation. In contrast, smart bioinks, capable of dynamically alter the material properties over time have the potential to interact with living organisms through reciprocal feedback, where the hydrogel instructs the organism and the organism causes the hydrogel to adapt. Thus, future bioinks may be able to adapt and “mature” along with the maturation of encapsulated cells to form truly functional tissue

Smart bioinks often include peptide and protein molecules found in the natural extracellular matrix. These molecular recognition motifs enable cell-surface receptors to bind to the bioink, allowing cell-detection of matrix mechanics. These smart materials’ rheological properties and gelation kinetics can be controlled by varying their monomer concentration or supplementing with additives to reduce printing-related cell damage. Smart bioinks do not only have excellent printability and shape-fidelity, but some might enable reversible switching of their rheological properties to support complex, hierarchical structures. Furthermore, the smart bioinks may enable more efficient application of mechanical stimulation to encapsulated cells to simulate external forces exerted in shearing, compressing, or stretching bioreactors.

By combining dynamic control of hydrogel mechanics and biochemistry with synthetic biology, smart bioinks have a high potential to form truly functional tissues. However, in these newly bioinspired ecosystems, the roles and tasks of cells and biomaterials might need to be newly defined.


Source: Blaeser et al. (2019) Smart Bioinks as de novo Building Blocks to Bioengineer Living Tissues, Gels 5(2), 29;




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