Page 10 - IJB-3-1

In vitro pre-vascularization strategies for tissue engineered constructs–Bioprinting and others

for large 3D tissue constructs as the time taken for in duced by bioprinting, showcasing the ability to pro-
vivo vascularization may be too long causing necro- duce viable tissue with customizable architecture [31] .
sis before a functional vascular network is formed, Novel laser-based bioprinting approaches have al-
leading to premature failure of the construct. This so been developed in recent years including the La-
disadvantage has driven many researches to develop ser-Induced-Forward-Transfer (LIFT) technique and
in vitro vascularization techniques to fabricate pre- stereolithography (SLA). The LIFT technique in-
vascularized tissue constructs before implantation, volves the focusing of a high powered laser beam onto
which has clear advantages over un-vascularized con- a photo-absorbent material coated with biological ink.
structs. The use of in vitro pre-vascularized tissue When the photo-absorbent material is exposed to suf-
constructs would speed up the process of anastomosis ficient laser intensity it vaporizes and causes a high-
with host vasculature and provide cells with quick pressure zone which propels a small volume of bio-
access to a nutrient supply [26] . We will now look at the logical ink onto a donor slide where the ink is col-
current methods developed by various research groups lected. By controlling the laser intensity and axial mo-
to fabricate blood vessels in vitro, and discuss their tion, high resolution patterns of biological material
advantages as well as disadvantages. can be printed [33,34] . Stereolithography was patented in

3.1 Bioprinting the 1980’s but only recently has the technology found
applications in the field of tissue engineering as re-
The term bioprinting refers to any additive manufac- searchers demonstrated its ability to be used for cell
turing technique which uses biological ink to produce encapsulation and the fabrication of 3D tissue scaf-
living tissue constructs for a variety of applications folds. Projection stereolithography (PSL) has been
including regenerative medicine and cellular stud- utilized to fabricate living tissue constructs with con-
ies [27] . There are numerous bioprinting techniques wh- trollable, porous architecture and demonstrated that
ich rely on fundamentally different principles of fa- cell viability was improved due to enhanced nutrient
brication such as extrusion, ink-jet, and laser-based delivery within the porous scaffolds compared to solid
approaches. Bioprinting technology has been a hot scaffolds [35] . Commercially available SLA systems
topic of research in recent years, given its potential have also been modified to improve and expand the
advantages over other conventional techniques, with system capabilities for tissue engineering applications
research groups striving to improve the performance such as the ability to fabricate 3D tissue constructs
of existing bioprinters as well as developing new bio- comprising distinct layers of different cell types and
printing technologies. This pursuit has given rise to material composition, thus improving the long-term
novel bioprinting technologies in recent years such as viability of encapsulated cells [36] .
the development of the “freeform reversible embed- The bioprinting approach has also shown potential
ding of suspended hydrogels” process, able to produce applications in the field of vascularization of tissue
3D constructs with complex architecture not achieva- constructs. A key advantage of using bioprinting
ble by conventional approaches [28] . Today, advan- technology is the ability to fabricate truly three-di-
ced bioprinters with state-of-the-art features such as
temperature and viscosity are now commercially ava- mensional microchannel networks which are perfusa-
ilable in the market, and researchers have been utiliz- ble and can be lined with ECs. These 3D networks
ing these bioprinters to produce groundbreaking rese- can be fabricated into pre-designed patterns which
arches. Researchers have demonstrated the ability of bio- could be useful in studying the effects of vascular
printing technology to fabricate hybrid constructs network spatial organization. Using a newly devel-
made of multiple hydrogel materials and cell types, oped extrusion-based bioprinting approach, 3D tissue
offering control of the construct’s mechanical stiffness constructs consisting of multiple cell types were suc-
and composition [29] . Scaffold-free, large diameter tu- cessfully produced and Human Umbilical Vein Endo-
bular tissue constructs have also been produc- thelial Cells (HUVECs) were observed to line the lu-
ed by bioprinting for vascular tissue engineering ap- men of embedded microchannels simulating perfusa-
plications using an indirect agarose molding techni- ble blood vessels [37] . Microchannel networks were
que [30] . The technique offers control of the tube’s sh- incorporated into the bulk ECM through the bioprint-
ape, dimension and hierarchical branching. The same ing of fugitive ink which was later removed, leav-
approach was utilized to fabricate fused toroid-shaped, ing behind microchannels which were then seeded
scaffold-free tissue from an alginate-based mold pro- with HUVECs. A similar study, using the same prin-

6 International Journal of Bioprinting (2017)–Volume 3, Issue 1