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

Abstract

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.

4D Cell-Condensate Bioprinting

“…[44] Several reports to date have shown the feasibility of using cytocompatible polymers as bioinks to print high-resolution hydrogel constructs. [30][31][32][33][34][35]45] In these studies, cells were either seeded on the hydrogel surface or encapsulated inside the formed hydrogels. However, the seeding of cells on the hydrogel surface fails to replicate the 3D cellular microenvironment, while encapsulation of cells inside the hydrogels interferes with critical cell-to-cell interactions.…”

“…[32] In a recent study, 4D digital light printed (DLP) silk hydrogels were applied as implants for treatment of a damaged trachea. [33] We also developed a series of biopolymer-based [34] and microgel-based [35] bioinks as versatile bioprinting platforms.…”

Stop-Flow Lithography for the Continuous Production of Degradable Hydrogel Achiral Crescent Microswimmers

“…In recent years, a heavier emphasis was placed on the practical applications of these microswimmers; thus, improving the degradability of microrobots to reduce the physical legacy impact of the microswimmers after finishing biomedical or environmental monitoring tasks has become one of the most pressing issues. Many degradable hydrogels have been successfully used to prepare microswimmers, such as poly (ethylene glycol) diacrylate (PEGDA), gelatin methacryloyl (GelMA), and poly (lactide-co-glycolic acid) (PLGA) [ 10 , 11 , 12 , 13 , 14 , 15 ]. Peters et al fabricated the helical hydrogel microswimmers for theranostic cargo delivery using two-photon polymerization [ 16 ].…”

Nanoengineered Granular Hydrogel Bioinks with Preserved Interconnected Microporosity for Extrusion Bioprinting

“…Despite the recent advances in fabricating microgel-based granular hydrogels for tissue engineering, additive manufacturing of them is not as trivial as bulk hydrogels. Microgels fabricated from various biomaterials, such as polyethylene glycol, [20][21][22] chitosan, [23] alginate, [24] gelatin, [25][26][27] and acrylic polymers, [28] have been explored in bioinks, [20,29] spheroid fabrication, [23] and stimuli-responsive constructs. [24] While bulk hydrogels may readily be rendered with shear-thinning properties for extrusion-based bioprinting, granular hydrogels attain such rheological behavior only when they are in a "jammed" (tightly packed) state [29][30][31] or are embedded in a viscous matrix.…”

“…Microgels fabricated from various biomaterials, such as polyethylene glycol, [20][21][22] chitosan, [23] alginate, [24] gelatin, [25][26][27] and acrylic polymers, [28] have been explored in bioinks, [20,29] spheroid fabrication, [23] and stimuli-responsive constructs. [24] While bulk hydrogels may readily be rendered with shear-thinning properties for extrusion-based bioprinting, granular hydrogels attain such rheological behavior only when they are in a "jammed" (tightly packed) state [29][30][31] or are embedded in a viscous matrix. [25,32] However, tightly packing or matrix-embedding 3D bioprinting of granular hydrogels comprising discrete hydrogel microparticles (microgels) may overcome the intrinsic structural limitations of bulk (nanoporous) hydrogel bioinks, enabling the fabrication of modular thick tissue constructs.…”