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gelatin, or a combination of PEGDA and GelMA additive elements in the bioinks [150] . PCL and
were used as the scaffold material for printing skin Poly (propylene fumarate) are polymers utilized
models [145-147] . in bioprinting due to its superior viscoelastic
and rheological properties, biodegradability,
5 Bioinks used in iPSC bioprinting and biocompatibility compared to the natural
Native tissue has complex architecture consisting compounds. Synthetic hydrogels such as PEGDA
of different cell types, ECM materials, growth are used as resins in 3D bioprinting, where cells
[147]
factors, and many signaling molecules. ECM is can be entrapped . The major limitation of these
organized in a highly delicate manner in a tissue kind of hydrogels is that the bioprinted structure
to serve the tissue specific functions such as shape, tends to collapse because of low viscosity and
consistency, mechanical strength, and molecular low mechanical strength [151] . New generation
miscibility. Bioinks are cell laden hydrogels bioprinters have enabled us to print combinatorial
containing ECM components of the tissue to be bioinks with spatial and nanoscale resolution in
printed. The materials used in the bioinks should seamless swift ways, aiming to reproduce the
be biocompatible without eliciting any undesirable complex architecture of the native tissues. There
response inside the body, should allow seamless are different types of bioinks available depends
printing, and should have tissue compatible up on the tissue structure. One example is that
rheological properties . The bioink components researchers bioprinted hepatic tissue constructs
[56]
can be natural, synthetic, different types of cells, using iPSC derived hepatocytes, endothelial
and soluble growth factors specific for the cell cells, and mesenchymal cells resuspended in two
types used. Natural polymers such as collagen, different bioinks; GelMA with stiffness similar
gelatin, fibronectin, laminin, and silk fibroin to healthy liver tissues, and a mix of glycidyl
have been widely used in bioinks to augment cell methacrylate-hyaluronic acid/GelMA which
attachment and migration in the matrix material [148] supported vascularization [73,152] . New generation
Polysaccharides such as alginate, agarose, and polymers responsive to light, thermal, magnetic,
chitosan are also widely using in bioinks. Alginate humidity, and pH stimuli would allow the 3D
is obtained from a type of brown algae and is widely bioprinting to leap to the next level.
used in 3D bioprinting applications due to its 6 Challenges associated with the use of
biocompatibility, promotion of cell proliferation, reprogrammed iPSCs and bioprinting:
low price, and the ability of crosslinking in
calcium ion solutions. However, alginate lacks The combinatorial application of 3D bioprinting
sufficient mechanical stiffness for 3D bioprinting. and iPSC technologies would have a major impact
Agarose is another biocompatible polysaccharide on regenerative medicine research. However, how
but it liquifies above physiological temperatures. much have we achieved to take this technique to
Chitin and chitosan obtained from crustaceous clinics and how far we have to go? Many obstacles
animal are widely used polysaccharide component still remain regarding the production of safer
of bioinks, but it is slow in solidification. The iPSCs that are to be resolved to take full advantage
methacrylated form of gelatin (GelMA) is a of this technology for therapeutic purpose .
[67]
popular bioink component to print iPSCs which One of the most important problems is the use of
possess easily tunable physiochemical properties retroviral and lentiviral vectors to introduce the
to use in bioprinters [149] . transcription factor genes into somatic cells for
Still, many of these polysaccharides are too cell reprogramming, which can cause mutagenesis
fragile and lack sufficient mechanical strength and tumor induction in the host cell. The iPSCs
to retain in the transplant tissue site and often derived using viral vectors may be still suitable
suffer from low mechanical properties, and for the study of disease mechanisms or for drug
thus, other materials have been combined as testing but they lack the suitability for clinical
International Journal of Bioprinting (2020)–Volume 6, Issue 4 71

