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International Journal of Bioprinting Bioprinted organ-on-a-chip with biomaterials

Table 1. Characteristics of frequently used natural biomaterials for 3D bioprinting
Biomaterials Advantages Limitations Crosslinking methods Reference
Collagen Good biocompatibility; Low shape fidelity Thermal crosslinking 37
most commonly used
Gelatin Good physical properties; Sensitive to thermal stimuli UV photocrosslinking 42
thermal reversibility
Alginate Rapid crosslinking ability; Low bioactivity Ca ionic crosslinking 46
2+
elasticity after crosslinking
Silk fibroin Good tensile properties; reconcilable Issue with cell adhesion Physical 52
degradability crosslinking
dECM Various ECM components; powerful Low shape fidelity Thermal crosslinking 56
tissue specificity
Abbreviations: dECM: decellularized extracellular matrix; ECM: extracellular matrix.

46
37
most commonly used. Therefore, due to these favorable with divalent cations. However, owing to the absence of a
characteristics, collagen serves as a prominent biomaterial cell attachment ligand, alginate is mainly used as a bioink
in various in vitro models, including organ-on-a-chip. in 3D bioprinting, either by mixing it with other hydrogels
However, collagen does come with limitations, such as poor or chemically modifying the binding site to enhance
physical properties, that may lead to the deformation of the biological activity. To address this limitation, collagen,
47
fabricated structure and a reduction in printing resolution. gelatin, and SF have been individually incorporated
Additionally, collagen undergoes rapid shrinkage upon into alginate, creating a hybrid bioink applicable to 3D
curing, rendering it unsuitable for the manufacturing of bioprinting. 48-50 These hybrid alginates exhibit adjustable
organ-on-a-chip with complex structures or significant viscosity and rapid gelling properties, rendering them
heights. To address these limitations, pure collagen is advantageous for fabricating complex organ-on-a-chip
38
subject to chemical denaturation or mixed with other structures and enhancing the stability of the structures. 51
hydrogels, such as alginate, which has been known for Silk fibroin, derived from Bombyx mori (silkworm),
its favorable physical properties. A recent development is recognized for its ease of processing, high mechanical
39
involves a hybrid collagen-derived hydrogel, wherein strength, controllable degradability, and excellent
the physical properties were enhanced through the biocompatibility, making it a prominent biomaterial
incorporation of photocurable materials. This innovative for tissue engineering. However, the direct use of pure
52
approach is actively used in the manufacturing of organ- SF in 3D bioprinting poses challenges due to its long
on-a-chip. 40
crosslinking time, low viscosity, and the tendency to cause
Gelatin is a collagen-modified protein extracted from frequent nozzle clogging during the printing process.
53
mammalian tissues. It is non-cytotoxic, biodegradable, Therefore, SF is primarily used in 3D bioprinting through
41
and features an arginyl-glycyl-aspartic acid (RGD) motif physicochemical transformations of pure SF or by mixing
that promotes cell binding. Additionally, gelatin exhibits it with a high-viscosity hydrogel or supplement to create an
42
thermoresponsive behavior, rendering it a preferred advanced SF-based hydrogel. 54
biomaterial for bioink in 3D bioprinting. However, due Decellularized ECM is a biomaterial obtained by
to its hydrophilic nature, gelatin is sensitive to moisture selectively removing cells from an organ while preserving
and becomes fluid above a certain temperature. This its ECM. This unique feature allows the implementation
55
sensitivity can pose challenges to the structural stability of of an organ-specific microenvironment—a challenge often
organs-on-a-chip manufactured using gelatin. To solve encountered with single-component-based biomaterials—
43
this problem, gelatin methacryloyl (GelMA), a modified and is made possible by the presence of organ-specific ECM
version of gelatin with improved printability and structural with dECM. Therefore, dECM stands out as a promising
stability, has been prepared via rapid ultraviolet (UV) biomaterial in tissue engineering and organ-on-a-chip
photocrosslinking. GelMA has gained widespread use as a fabrication through 3D bioprinting; accordingly, dECM
hydrogel in tissue engineering applications. 44
56
bioinks have been developed for various organs. The use
Alginate, a polysaccharide extracted from seaweed, is of dECM bioink in 3D bioprinting enhances cell viability,
45
widely used in 3D bioprinting due to its cost-effectiveness, tissue-specific gene expression, and organ-specific activity
controllable mechanical and rheological properties, and of cells. However, the dECM bioink application comes with
the ability to undergo immediate crosslinking reactions limitations, including non-uniform ECM composition

Volume 10 Issue 1 (2024) 24 https://doi.org/10.36922/ijb.1972