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Bioprinting of artificial blood vessels

In 4D bioprinting, the printed constructs are able to and existing vessels. Vascularized constructs need to
evolve over time after being printed, alter their shapes have these two components for successful host-implant
and functionalities in response to external stimuli [70] . anastomosis: (1) hierarchy of vessels with different
As bioprinting of vascularized tissue advances, the lumen sizes that are approximately within 200 μm of one
preservation and culture of tissues would be a focus another to provide sufficient diffusion to surrounding
in the future for accurate pre-operation conditioning cells and (2) well defined vascular geometry such as
and the transplanted bioprinted constructs would be branching pattern and angle to match the metabolic
expected to remain integrated with the vascular system profile of native tissues [73] . For autonomous vascular
of the recipient post-operation, without collapsing or structures of certain sizes, it is possible for surgical
obstruction. However, 4D bioprinting is still more of anatomosis and suturing of fabricated vessels with
a hypothesis and is waiting to be validated. Figure host. Zhang B, et al. successfully fabricated vascular
2 provides a simple overview on the three methods construct and connected them to femoral vessels on the
[71]
employed in 4D bioprinting . hind limbs of adult rats with surgical cuffs. Perfusion
Currently, there might be more potential for was established immediately after surgery and it was
vascularized constructs to be used for in vitro disease reported that the vessels remained clot-free up till one
model studies or drug screening studies. However, week after surgery. In addition, native angiogenesis was
despite all these facts, currently there is no definite also reported to be observed around the implant with
evaluation criteria for tissue-engineered blood vessels endothelial cells subsequently coating the lumen in
[74]
and hence it is hard to compare between different the implants . Such surgeries might be more invasive
bioengineered models and designs. Therefore, there is than traditional treatment methods. In addition, surgical
a need to develop standard evaluation criteria in order anastomosis is only available for vascular structures
to improve our common understanding and to work that are of a certain size with equivalent mechanical
towards a common standard. There are numerous novel properties to withstand pulsatile nature of blood flow
approaches in overcoming some of the problems that we and stretch. Vascular constructs with micro-vessels
are facing currently. One approach would be bottom- often has to rely on natural anastomosis induced by
up fabrication, which includes the manufacture of mini- host or construct. These vessels are often too small and
tissue constructs as building blocks and joining them numerous to be directly sutured. Song, et al. recently
together, forming a tissue construct with clinically- published an in depth review on the natural anastomosis
relevant volumes. A new kind of scalable bioink, “tissue mechanisms that were currently proposed: (1) effects
strands”, for scaffold-free bioprinting was introduced of cellular and biomolecular compositions, (2) effects
recently. These tissue strands are bioprintable and can of vascular architectures, (3) establishment of cell-cell
facilitates rapid fusion and maturation through self- contact via adherin and tight junctions, (4) polarization
assembly without the need of a support moulding of fused tip cells and (5) blood pressure driven
structure nor a liquid delivery medium during extrusion. invagination of apical membranes [75] . In short, even
These unique characteristics enable scale-up constructs though there were reported articles on the positive effects
and may one day enable the integration of macro-scale of high density fibroblasts or fibroblast on anastomosis,
vascular networks in bottom-up fabrication which would most of these studies were stand-alone studies with
be a promising tool in obtaining vascularized tissue unclear understanding of the exact mechanisms [76,77] .
with clinically-relevant size in the future [72] . Another Further investigations from different professionals are
popular approach is the utilization of decellularized required to piece the missing information and provide
matrix as bioink for the fabrication of biomimetic tissue future potential strategies for host-implant anastomosis.
constructs. Since decellularized matrix is derived from 4. conclusion
native tissue’s own scaffold, it is believed to be closer
in relation to native tissue and thus is able better mimic Since the last decade, significant advances have been
the anatomical and functional features of the native made in respect to bioprinting of artificial blood vessels.
microenvironment, providing tissue-specific cellular Despite having several positive results in the generation
cues that are required to enhance overall cell viability of functional vascular tissue, there are still obstacles to
[65]
and organization as well as functionality . Advances in be solved if we want to biofabricate clinically-relevant
vascular and tissue engineering could provide a potential constructs. There is increasing needs for vascular grafts
source for grafts and solve the problems in autologous and vascular engineering is deemed as the potential
and homologous transplants. As we are able to fabricate way ahead for replacing autologous and homologous
larger and larger vascular constructs and autonomous grafting. Continued innovation and advancements in
vascular structures, there is also a need to consider vascular engineering, vascular biology, nanotechnology,
the need for anastomosis between bioprinted vessels material science and bioprinting are required to motivate

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