Stem cell-laden hydrogel bioink for generation of high resolution and fidelity engineered tissues with complex geometries

Abstract

Recently, 3D bioprinting has been explored as a promising technology for biomedical applications with the potential to create complex structures with precise features. Cell encapsulated hydrogels composed of materials such as gelatin, collagen, hyaluronic acid, alginate and polyethylene glycol have been widely used as bioinks for 3D bioprinting. However, since most hydrogel-based bioinks may not allow rapid stabilization immediately after 3D bioprinting, achieving high resolution and fidelity to the intended architecture is a common challenge in 3D bioprinting of hydrogels. In this study, we have utilized shear-thinning and self-healing ionically crosslinked oxidized and methacrylated alginates (OMAs) as a bioink, which can be rapidly gelled by its self-healing property after bioprinting and further stabilized via secondary crosslinking. It was successfully demonstrated that stem cell-laden calcium-crosslinked OMA hydrogels can be bioprinted into complicated 3D tissue structures with both high resolution and fidelity. Additional photocrosslinking enables long-term culture of 3D bioprinted constructs for formation of functional tissue by differentiation of encapsulated human mesenchymal stem cells.

Graphical abstract

Highlights

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  Hydrogel bioink system with shear-thinning and rapid self-healing properties.

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  Bioprinting of constructs with high shape fidelity and mechanical stability.

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  3D printing of complex structures including precisely defined overhang geometries.

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  Potential to spatially control bioprinting of tissue-specific bioinks.

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  Independent spatial control of printed hydrogel physical and biochemical properties.