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International Journal of Bioprinting 3D bioprinting for vascular system

Blood vessels’ development and maturation process is 6. Conclusion
very complex, involving the precise regulation of multiple Cardiovascular diseases, a collection of non-infectious
biological, chemical, and physical stimuli in chronological diseases with the highest mortality rate globally, put forward
order. Currently, bioprinting can only be used to create huge clinical demand for functional vascular grafts. As
a static angiogenic environment and print blood vessel the technical bottleneck of organ transplantation, how to
grafts containing pro-angiogenic factors. In addition, construct a microvascular network for material exchange in
the vascular cells in grafts lack dynamic biochemical and thick tissue is also the research focus of tissue engineering
mechanical stimuli that help recapitulate the physiological technology. 3D bioprinting uses computer modeling to
complexity of native blood vessels.
accurately make complex pre-designed anatomical structures
To address this challenge, the post-processing from cells and biological materials, providing a new way
of bioprinting is significant. A bioreactor is a device to overcome the shortage of blood vessel donors and the
specifically designed to cultivate and stimulate the bottleneck of organ transplantation technology. In this
development of engineered tissues. McFetridge et al. review, we summarize and discuss functional vascular grafts
developed a modular bioreactor and perfusion system that and thick tissues prepared by 3D bioprinting technology
allows vascular structures to grow and increase during from three aspects: large vessels and valves, small vessels, and
an extended culture period . Perfusion bioreactors can microvascular networks, according to the anatomical caliber
[73]
provide a constant supply of nutrients for blood vessel classification of the human vascular system. The large blood
development and accurately replicate the hemodynamic vessel grafts manufactured by 3D bioprinting can effectively
stimulation of natural blood vessels, including pressure, solve the problems of inconsistent anatomy between
strain, flow rate, and wall shear stress. electrospun grafts and host, and low cell survival rate. The
The physical environment in which blood vessel cells complex heterogeneous structure of the valve is closely
live is crucial for cell maturation. Hemodynamic shear related to its special physiological functions. With the help
stress is an essential determinant of endothelial function of computed tomography scanning, computer modeling,
and phenotype. Wang et al. designed an in vitro flow and 3D bioprinting technology, it is possible to prepare
adjustable vascular bioreactor system (VesselBRx) and biocompatible valves with good mechanical properties. 3D
demonstrated that under low-flow culture conditions, the bioprinting technology can directly and accurately deposit
intima of small-caliber vascular grafts thickened 2.5 times vascular endothelial cells and smooth muscle cells to construct
within 7 days, accompanied by a loss of 80% lumen endothelialized small-diameter grafts with good biological
area . In contrast, under high-flow culture conditions, properties, which effectively solve the high occlusive rate of
[74]
no neointima was observed. Under low-flow conditions, small-caliber vascular grafts. High-resolution 3D bioprinting
the endothelial cells no longer formed a single layer but technology can design vascular micropatterns that guide
extended into the cavity as a multi-layer structure. Under angiogenesis and multi-dimensional vascular network layers
high-flow conditions, the endothelial cells physiologically that adapt to the host vascular system, which are the key
remained as a monolayer with a vascular structure differences between 3D bioprinting technology and other
comparable to natural controls. This result indicates that tissue engineering technologies. Combined with bioactive
the traditional static culture method cannot effectively inks, 3D bioprinting technology can provide effective physical
maintain the normal physiological state of blood vessel cues and biological stimuli for angiogenesis in thick tissues.
cells, and bioreactors can provide sufficient hydrodynamic In the future, high-resolution printing technology
stimulation for vascular development and inhibit abnormal and biological ink with good biological and mechanical
intimal hyperplasia . Syedain et al. used pulsed fluid properties will remain the research hotspot and key
[74]
stimulation to promote the proliferation of fibroblasts to 3D bioprinting technology. The emerging artificial
in vascular grafts . After 9 weeks of bioreactor culture, intelligence can further improve the accuracy and
[75]
vascular grafts could withstand bursting pressures in the resolution of bioprinting technology. In addition, the rise
range of 1400–1600 mmHg, and their compliance was of smart materials has spawned the concept of 4D printing.
comparable to that of autologous arteries . In addition, Compared with the static structures generated by 3D
[75]
artificial blood vessels produced from this bioreactor have bioprinting, 4D bioprinting allows 3D-printed structures
been transplanted surgically in ten patients with end-stage to change their configuration or function over time in
renal disease requiring hemodialysis access . In light of response to external stimuli, such as temperature, light, and
[76]
the above, in-depth investigations into the cultivation and water, thus bringing 3D printing to life. Endowing vascular
maturation of small-caliber vascular grafts in bioreactors grafts with the ability to respond to natural vascular
are instrumental in effectively translating the fundamental environmental stimulation through innovative materials
bioprinted samples into the real-life clinical applications. is also a possible future research direction for bioprinted

Volume 9 Issue 6 (2023) 268 https://doi.org/10.36922/ijb.0012