Jammed Micro‐Flake Hydrogel for Four‐Dimensional Living Cell Bioprinting

• Published in: Advanced materials (Weinheim) Vol. 34; no. 15; pp. e2109394 - n/a
• Main Authors: Ding, Aixiang, Jeon, Oju, Cleveland, David, Gasvoda, Kaelyn L., Wells, Derrick, Lee, Sang Jin, Alsberg, Eben
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.04.2022
• Subjects: bioinks; Bioprinting - methods; Cartilage; Cells (biology); Composition; cross‐linking gradient; Flakes; four‐dimensional printing; Hydrogels; Materials science; Microgels; Morphing; Photoinitiators; Physical properties; Printing, Three-Dimensional; shape morphing; Size distribution; Three dimensional printing; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds; bioinks; shape morphing; four-dimensional printing; tissue engineering; cross-linking gradient
• ISSN: 0935-9648; 1521-4095; 1521-4095
• DOI: 10.1002/adma.202109394

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 cross‐linked to form a gradient in cross‐linking 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 are obtained. Based on this system, 4D cartilage‐like tissue formation is 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) are 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. A controllable cross‐linking gradient in the 3D printed bioconstructs is achieved, enabling predefined shape transformations. 4D tissue engineering is demonstrated in a 4D cartilage‐like tissue regeneration study.