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3D bioprinting technology for regenerative medicine applications

ton, SC and 3D-Bioassembly Tool (BAB) developed example, thermal inkjet printers require bioinks of
by Scipero, Orlando USA have been developed to lesser thermal conductivity to improve the cell viabil-
construct 3D tissues/organs. Though BAB is still in its ity [73] . Biocompatibility is another important facet of a
infancy, this method can evolve as a promising solu- biological construct aimed for regenerative medicine
tion to create patient-specific tissue constructs for re- applications [74] . Bioinks should be biocompatible and
generative medicine applications [33,70,71] . However, provide a favorable milieu to the cells. The degradation
lack of scalability and problems with precise printing profile of the constructs should be in tune with the
are the major drawbacks of the current robotic bio- regeneration of new tissues [75] and the degradation
printers. Recently, Advanced Solutions (Kentucky, products of the constructs should not cause any adverse
USA) has developed a six-axis robotic dispensing bi- reactions. Most importantly, bioinks should provide
oprinter that can efficiently handle curves and allows mechanical support and structural support to the
precise printing of the structures. The main advantage growing cells to maintain 3D microenvironment. Bio-
of this method is its software, TSIM (TSIM-Tissue inks should have biomimetic properties to have a pos-
Structure Information Modeling) that can perform an itive influence on the cell adherence, proliferation and
MRI scan of human tissue and convert it into a printa- other functionalities [76] . An ideal bioink should also
ble 3D shape. Robotic bioprinters and tissue spheroid possess tunable gelation properties and easy to make
encapsulators are well developed commercially avail- chemical modifications to improve the biological fun-
[1]
able OBL components. However, high-performance ctionalities . These attributes are essential for an ideal
perfusion bioreactors are yet to be developed to im- bioprinting material/bioink. The following section will
prove organ printing. The existing technological chal- give detailed descriptions about bioink materials.
lenge is to develop a complete and perfect OBL to
print organs at a larger scale for regenerative medicine 5.1 Natural Polymers
applications. (1) Alginate
Sodium alginate (alginate) is a raw material ex-
5. Bioinks for 3D printing tracted from brown seaweed. Alginate is a polysac-

The 3D printing technology was initially developed for charide and anionic in nature. It is a linear block co-
many non-biological applications that involve the use polymer having M (β-D mannuronic acid monomers)
of high temperature and toxic organic solvents. These and G (α-L-guluronic acid blocks) domains. Alginate
harsh conditions are not suitable for printing biological structure has a mixture of M and G domains. G-blocks
cells and other biomaterials. Hence, it is essential for can form ionic bonds when interacts with divalent
printing to find suitable bioinks with desired functional cations and become gels in solutions. Biomimetic
and mechanical properties in order to come close to structure, suitable viscosity, gelation at ideal tempera-
native tissue. Both natural polymers (such as collagen, tures and high biocompatibility are some of the prop-
gelatin, alginate, fibrin, hyaluronic acid and chitosan) erties of alginate that makes it suitable for bioprint-
and synthetic polymers (such as polyethylene glycol ing [77–81] . Cell-laden 3D alginate hydrogels were pre-
(PEG), poly(L-lactic acid) (PLA) and poly(ε-caprolac- pared using inkjet printing [81] . Although this hydrogel
tone)(PCL)) are predominantly used as bioinks. Ul- provides biocompatibility and mechanical strength, it
trashort peptides that can self-assemble into nanofibr- lacks cell recognition motifs. Moreover, bioprinting
ous structures have recently been proposed as novel alginate constructs of thick tissues with well inter-
bioinks and are attractive candidates for bioprinting connected pores is yet to be achieved.
due to biocompatibility and processability [72] . This ne- (2) Collagen and Gelatin
wly developed bioink contains helical fiber structures Collagen is a naturally occurring protein in tissues
that strongly resemble collagen fibers in topography which constitutes largely of amino acids such as hyd-
and diameter [72] . roxyproline, proline, glycine and trace amounts of su-
Printability is an important feature of an ideal bioink. lfur containing amino acids and aromatic amino acids.
During printing, the bioink should be accurately depo- Hydroxyproline and proline maintain the tertiary stru-
sited in the construct providing the desired temporal cture of the collagen. Collagen is a major extracellular
and spatial resolution. Bioinks should also enhance the matrix (ECM) protein and controls all the cellular fate
cell viability post-printing and must have desired phy- processes [82] . It is used as a scaffold material for vari-
sico-chemical properties to suit the printing needs. For ous tissue engineering applications; however, its poor

16 International Journal of Bioprinting (2016)–Volume 2, Issue 2