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

Table 1. Characteristics possessed by each of the five techniques described
Bioprinting Microfluidics Micropatterning Wire molding Cell-sheet
Vascularization of thick 3D tissue
Control of tube dimensions
Control of network architecture
Perfusable networks
Multicellular vascularized tissue
Suitability for in vitro models
Tubulogenesis through self-assembly
Ability for vascularized tissue to be harvested for downstream experiments

and stacking only requires slight thermal treatment With the increasing flow of research into bioprint-
which does not significantly harm the cells. Thirdly, ing technology, it is not surprising that the technology
the ability to form thick layers of vascularized tissue has experienced a rapid boost in development. Bio-
and control over the orientation of vascular networks printing technology now allows us to print multicellu-
has been demonstrated using cell sheet technology. lar constructs with high precision which mimics the
hierarchal architecture of native tissue. It also pos-
4. Conclusion
sesses the ability to fabricate perfusable 3D micro-
In vitro vascularization techniques play a critical role channel networks within bulk tissue which is particularly
in the advancement of tissue engineering. In the field useful in our efforts to achieve in vitro vascularization.
of regenerative medicine, scientists have identified Compared to other technologies like photolithogra-
vascularization as a key hurdle that needs to be over- phy, bioprinting is young in terms of its development,
come. To date, the variety of tissue-engineered prod- thus it has the potential to be improved significantly
ucts successfully translated for clinical use has been and to find new applications in the years ahead.
limited to thin avascular tissue due to the inability of We believe that bioprinting represents the future of
current technology to incorporate functional vascular tissue engineering and could potentially evolve into be-
networks into thick tissue constructs. The ability to coming the gold-standard of biofabrication technology.
fabricate physiologically accurate in vitro tissue mod-
els has also been hindered by the lack of effective in Conflict of Interest and Funding
vitro vascularization techniques. Although 2D vascu- No conflict of interest was reported by all authors.
lar models have been successfully fabricated and Y.Z. acknowledges the Tier-1 Academic Research
proven their efficacy, thick 3D vascular models re-
main elusive. Today, biologists and engineers are Funds from the Singapore Ministry of Education
working hand in hand to develop working techniques (RGC 1/14), the A*STAR Industrial Robotics Pro-
for in vitro vascularization. We have described several gramme (1225100007) and the SHS-NTU/017/2016.
enabling techniques being developed today which References
show promising signs of being able to achieve this
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14 International Journal of Bioprinting (2017)–Volume 3, Issue 1