Applications of Gelatin Methacryloyl (GelMA) Hydrogels in Microfluidic Technique-Assisted Tissue Engineering

Abstract

In recent years, the microfluidic technique has been widely used in the field of tissue engineering. Possessing the advantages of large-scale integration and flexible manipulation, microfluidic devices may serve as the production line of building blocks and the microenvironment simulator in tissue engineering. Additionally, in microfluidic technique-assisted tissue engineering, various biomaterials are desired to fabricate the tissue mimicking or repairing structures (i.e., particles, fibers, and scaffolds). Among the materials, gelatin methacrylate (GelMA)-based hydrogels have shown great potential due to their biocompatibility and mechanical tenability. In this work, applications of GelMA hydrogels in microfluidic technique-assisted tissue engineering are reviewed mainly from two viewpoints: Serving as raw materials for microfluidic fabrication of building blocks in tissue engineering and the simulation units in microfluidic chip-based microenvironment-mimicking devices. In addition, challenges and outlooks of the exploration of GelMA hydrogels in tissue engineering applications are proposed.

Keywords: GelMA hydrogels; biomedicine; microfluidics.

Figure 1

(a) Extrusion method: strategy of bioprinting GelMA/alginate core/sheath microfibers into 3-D constructs with tunable microenvironments. Reproduced with permission [57]. (b) Laminar flow-based method: Capillary microfluidic device used for biomimetically constructing osteon-like double-layer hollow microfiber with the novel composite bioink. Reproduced with permission [59]. (c) Electrospinning method: The microdevice to generate microstructured GelMA fibers. Reproduced with permission [60].

Figure 2

Multiscale composite scaffold preparation based on a gelatin methacryloyl (GelMA)/chitosan microspheres (GC-MSs) modular bioink: GC-MS preparation by a microfluidic approach (step 1), nerve cells seeded on GC-MS (step 2), GC-MS/GelMA modular bioink preparation (step 3), bio-fabrication of 3-D composite scaffold performed by extruding bioink with the 3-D printer (step 4). Reproduced with permission [72].

Figure 3

(a) Fabrication procedure of tubular microstructures using on-chip fabrication and the assembly of toroidal cell-embedded microstructures. (b) Cell culture on GelMA microstructure after 2 days of different UV exposure. Reproduced with permission [83].

Figure 4

Schematic of the fabrication process for the hydrogel-based chip and its mechanism. Reproduced with permission [92].

Figure 5

(a) To model the different aspects of thrombosis and fibrosis, three different types of models were generated: endothelium covering the microchannel wall with no encapsulated fibroblasts in the matrix (control), encapsulated fibroblasts with no endothelial cells covering the microchannel, and both encapsulated fibroblasts in the matrix and endothelium covering the microchannel. (b) Photographs showing the infusion of human whole blood into the endothelialized microchannels and (c) the formed thrombosis-on-chip model. Reproduced with permission [94].

Figure 6

(a) Schematic diagram of the generation process of the hydrogel films. (b) Schematic and image of the heart-on-a-chip by integrating the rGO hybrid anisotropic structural color film into a bifurcated microfluidic system. Reproduced with permission [95].

Figure 7

The metastasis-on-a-chip platform. Reproduced with permission [96].