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International Journal of Bioprinting Liver printing: from structure to application
Figure 6. 3D printing strategies and material properties. (A) An ideal bioink fulfills three main roles: maintain cell viability; bioprintability; and direct
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cell behavior. Adapted with permission from Morgan et al. (B) Different printing strategies: inkjet bioprinting; extrusion bioprinting; laser-assisted
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bioprinting; and stereolithography bioprinting. Adapted with permission from Foyt et al. Abbreviation: UV, ultraviolet.
implant integration, and enhance wound healing and the requirement of a photoinitiator during photocuring,
tissue regeneration. These materials aim to achieve optimal which can be toxic to cells at higher concentrations. 106
effects within the host, embodying a concept termed
“immune interaction” materials. 111,112 4.1.2. Collagen
Collagen is the most abundant fibrous protein in mammals
Currently, several natural, naturally derived, and and a major component of the ECM. Collagen is composed
synthetic biopolymer-based materials can be used as of three left-handed peptide helices coiled together to
bioink. Natural materials include protein-based materials form a right-handed triple helix, with adjacent helices
such as gelatin, collagen, fibronectin, and silk fibroin; crosslinked at the end of each helical peptide bond. The
polysaccharide-based materials such as hyaluronic acid, resulting long fibrils can form much thicker bundles,
agarose, and alginate; ECM-based materials such as with their thickness determining the tensile strength of
decellularized ECM (dECM) and Matrigel; as well as connective tissue. Collagen contains RGD peptides,
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mixtures or derivatives of these natural materials. Synthetic supports cell adhesion, and is biodegradable with good
materials mainly include Pluronics and PEG. The main biocompatibility. Lee et al. encapsulated hepatocytes,
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components of the liver ECM include collagen, laminin, human umbilical vein endothelial cells (HUVECs), and
fibronectin, and proteoglycans. These materials are all human lung fibroblasts with collagen as a bioink, while
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ideal candidates for bioink. simultaneously printing polycaprolactone (PCL) scaffolds
to prevent collagen gel collapse and maintain structural
4.1.1. Gelatin integrity. The collagen bioink facilitated the formation of
Gelatin is a peptide mixture produced by the hydrolysis capillary networks, resulting in hepatocytes exhibiting
of collagen, retaining natural cell-binding motifs such good ALB and urea synthesis capabilities. 118
as RGD and matrix metalloproteinase (MMP)-sensitive
degradation sites. However, gelatin gels often lack thermal 4.1.3. Silk fibroin
stability and mechanical strength, thus necessitating their Silk fibroin is a naturally occurring high-molecular
combination with other materials or chemical crosslinking weight fibrous protein extracted from silkworm silk
for use as tissue culture materials. The addition of through a process of degumming. Silk fibroin possesses
methacrylate groups to the amine groups of gelatin forms excellent mechanical and physicochemical properties,
methacrylated gelatin (GelMA), a photocurable hydrogel such as flexibility, tensile strength, breathability,
material that is stable at 37°C. Due to its excellent cell moisture permeability, and controlled-release properties.
compatibility and mechanical properties, GelMA is widely Additionally, the gelation conditions are mild, making it
used in bioprinting. However, a drawback of GelMA is suitable for cell encapsulation. Fibroin is commonly used
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Volume 10 Issue 5 (2024) 130 doi: 10.36922/ijb.3819

