Jammed Micro-Flake Hydrogel for 4D Living Cell Bioprinting

• Published in: Advanced materials (Weinheim) Vol. 34; no. 15; p. e2109394
• Main Authors: Ding, Aixiang, Jeon, Oju, Cleveland, David, Gasvoda, Kaelyn, Wells, Derrick, Lee, Sang Jin, Alsberg, Eben
• Format: Journal Article
• Language: English
• Published: 17.02.2022
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202109394

Four-dimensional (4D) bioprinting is promising to build cell-laden constructs (bioconstructs) with complex geometries and functions for tissue/organ regeneration applications. The development of hydrogel-based 4D bioinks, especially those allowing living cell printing, with easy preparation, defined composition, and controlled physical properties is critically important for 4D bioprinting. Here, a single-component jammed micro-flake hydrogel ( MFH ) system with heterogeneous size distribution, which differs from the conventional granular microgel, has been developed as a new cell-laden bioink for 4D bioprinting. This jammed cytocompatible MFH features scalable production and straightforward composition with shear-thinning, shear-yielding, and rapid self-healing properties. As such, it can be smoothly printed into stable 3D bioconstructs, which can be further crosslinked to form a gradient in crosslinking density when a photoinitiator and a UV absorber are incorporated. After being subject to shape morphing, a variety of complex bioconstructs with well-defined configurations and high cell viability were obtained. Based on this system, 4D cartilage-like tissue formation was demonstrated as a proof-of-concept. The establishment of this versatile new 4D bioink system may open up a number of applications in tissue engineering. Single-component jammed micro-flake hydrogels (MFHs) were developed as cell-laden bioinks for 4D bioprinting. Cytocompatible MFH bioinks without the need of additional fillers are rheologically favorable for bioprinting via smooth direct ink writing (DIW). A controllable crosslinking gradient in the 3D printed bioconstructs was achieved, enabling predefined shape transformations. Ultimately, 4D tissue engineering was demonstrated in a proof-of-concept 4D cartilage-like tissue regeneration study.