Temperature-programmable and enzymatically solidifiable gelatin-based bioinks enable facile extrusion bioprinting (vol 12, 045003, 2020)
BIOFABRICATION(2020)
Abstract
The development of exceptional bioinks with excellent printability, high fidelity, and excellent cell viability maintenance for extrusion bioprinting remains a major challenge. Gelatin is an ideal candidate bioink due to its biocompatibility, biodegradability, and non-immunogenicity. However, its inherently low viscosity and unstable physical gelation under physiological conditions make it unsuitable for direct extrusion bioprinting of tissue-like gelatin constructs with high fidelity. Herein, sequential chemical modification using reversible quadruple-hydrogen-bonded ureido-pyrimidinone (UPy) and enzyme-responsive tyramine moieties (Tyr) were devloped to endow the gelatin with a temperature-programmable viscosity and enzyme-controlled solidification, thus realizing enhanced printability and superior fidelity. As demonstrated in a proof-of-concept study, various cell-laden constructs were built based on our modified gelatin, including two-dimensional human bone marrow mesenchymal stem cell (hBMSC)-laden patterns, three-dimensional interconnected hBMSC-laden scaffolds, a reversible twisting-tension human-scale hBMSC-laden ear, a bicellular tibia-like construct containing hBMSCs and endothelial cells and a hexagonal prism-shaped hepatocyte-laden scaffold. The loaded cells in the construct have high viability of over 90% at 24 h, and show proliferation and protein secretion over one week, suggesting that Gel-UPy-Tyr-based constructs under physiological temperature not only can keep high fidelity, but also can support the growth and functions of the loaded cells.
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Key words
gelatin-based bioink,bioprinting,temperature-programmable viscosity,UPy,enzymatic crosslinking
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