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Bioprinting of artificial blood vessels

effects of micro-environment on neovascularization. scaffold. As discussed by the authors, the challenge of
Bioprinted large skin constructs with ADSCs and bioprinting autonomous vascular scaffolds lie in finding
endothelial progenitor cells (EPCs) in decellularized the proper concentration and viscosity of hydrogels
extracellular matrix of skin showed faster and enhanced that has sufficient mechanical strength to support the
[66]
vasculogenesis via the self-assembly technique [63] . This weight of the entire structure . Other than properties of
group of constructs showed significantly higher number biomaterials, this study explored the effects of printing
CD31+ vessels as compared to cell-free scaffolds and parameters such as extrusion speed, nozzle diameter,
ADSCs with EPCs without scaffolds. In addition, such pressure, thickness of wall and number of layers so as to
3D printed constructs were found to have subsequently optimize future bioprinting processes.
higher level of blood perfusion on laser Doppler Droplet-based direct extrusion was also used in
perfusion imaging technique. This study showed biofabricating autonomous vascular structures. Early
the importance of micro-environment. Sole reliance works include using of a modified thermal ink-jet printer
on cell based therapy is insufficient in promoting to eject 30 to 50 μm droplets of smooth muscle cells
vasculogenesis. Therefore, micro-environment plays a encapsulated in sodium alginate into calcium chloride
huge role in inducing self-assembly of vessels. solutions. Alginate tubes with encapsulated smooth cells
were biofabricated with maintenance of cell phenotype,
2.3 Autonomous vascular Structures even distribution of cells, cell growth with 80% viability
Since the emergence of tissue engineering, most after 18 days of culture. Interestingly, to evaluate the
strategies had generally revolved around scaffold based functionality of their bioprinted constructs, the authors
engineering whereby cells are usually encapsulated in conducted a vasomotor reactivity test by exposing the
bio-inks. In the initial years, scaffolds were thought constructs to the vaso-constricting agonist Endothelin-1.
to be only providing cells with temporary support for Their results showed that the constructs contracted in a
cell growth. However, scaffolds have since evolved to dose-dependent manner with complete closure of lumen
[67]
be a critical factor in tissue engineering. Scaffolds are after 43 hours of exposure to 50 nM of Endothelin-1 .
thought to resemble the “extra-cellular matrix” of native In addition, the constructs showed dilation of lumen
micro-environment and certain structural properties of after removal of agonists. Even though it is difficult to
scaffolds are reported to be able to influence cellular make a direct comparison between these results and
differentiation into certain cell lines by providing native vessels or other vascular engineered constructs,
biological, chemical and mechanical cues [64] . Even it paved the way ahead for vascular tissue engineering
though there are certain level of clinical translation and demonstrated that the challenge lies in design of
of scaffold based vascular engineering, there are still functional tissues and that droplet-based direct extrusion
some unsolved challenges limiting complete clinical technique might be a possible solution to solving these
implementation. Firstly, there are currently no known problems. Working on similar principles, a team used a
biomaterial that have these following characteristics: static-electricity actuated ink jet system with modified
no or low induced inflammatory response in host, ink jet heads to dispense downsized micro alginate beads
degradation rates that are synchronous with tissue or of approximately 25 μm in size. This method allowed
vascular formations, degraded by-products that are non- superior control in fabricating 35-40 μm wall thickness
toxic and similar mechanical properties as native tissues. and 30-200 μm internal diameter fine tubular constructs.
Secondly, even after much research, we are still not able In this study, the authors demonstrated that droplet-based
to create the ideal structural properties of scaffolds that direct extrusion of scaffold free vascular constructs is a
are able to mimic the native extra-cellular matrix which promising alternative to overcoming limitations faced
plays a huge role in determining cellular activities. These by scaffold-based engineering and such a method has
challenges have led to increasing interest into fabrication the potential to biofabricate fine vascular structures with
[68]
of autonomous vascular structures without scaffolds. precise internal architectures .
On the other hand, such studies have revealed some A recent novel study developed a triple tunica layered
potential into small diameter blood vessel graft as we perfusable vascular-like structure using a self-made
are now able to biofabricate models with distinct tunica microfluidic platform, two concentric stainless steel
[65]
layers and high mimicry . needles and cell laden GelMA. Fibroblasts, smooth
A multi-nozzle extrusion-based technique was used muscle cells and endothelial cells were suspended in
to biofabricate a concentric alginate based tubular GelMA hydrogel. Fibroblasts-GelMA were pipetted into
construct. In this study, a nozzle of alginate-xanthum the outer concentric ring (between larger needle and
gum hydrogel was used to bioprint a 6 mm concentric wall of platform) and cross-linked with UV light before
scaffold with another nozzle dispensing calcium chloride removal of the larger needle. This led to the formation
into the internal surface of the alginate-xanthum gum of tunica adventitia-like vascular structure. Tunica

10 International Journal of Bioprinting (2018)–Volume 4, Issue 2