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3D Printing and Vascularized Organ Construction
channels formed when the gelatin was removed using techniques in printing complex structures and functional
phosphate-buffered saline. ECs were implanted in the characteristics is analyzed.
channels and perfused through a microfluidic method
and demonstrated certain viability . Likewise, various 4.1. Cardiovascular system
[72]
studies have proven that gelatin is a suitable sacrificial According to the World Health Organization statistics,
material as impermanent template for collagen-based cardiovascular diseases are among the highest incidence
vascular generation [73,74] . and mortality rates in the world . More than 17 million
[76]
Even though the utilization of a sacrificial template people die of heart diseases every year. Cardiovascular
is superior in geometrical and microfluidic aspects, diseases have become the leading cause of death in
constraints such as fabrication and feasibility are still developed countries, accounting for about 40% of the
encountered in the post-printing processes. The accurate total number of deaths. More than 1.4 million vascular
modification on the external of the vascularized network grafts are needed a year in the United States alone .
[77]
is difficult to conduct because of the surroundings of In China, the lower limb venous diseases and coronary
the hydrogel. Besides, an effective approach is needed artery bypass surgeries have increased dramatically along
to connect blood vessels by simulating natural vascular with the congenital heart disease rate 6.7/thousand .
[78]
networks with a complex design. Most of the previous The clinical demand for the vascular graft is increasing
studies are concentrated on the vascularized networks prominently. 3D printing of vascular structures can
which are placed horizontally or stacked vertically. These effectively solve the problem of graft shortage.
are limited methods to simulate the complexity of natural At present, autologous transplantation or
vascular networks. allogeneic transplantation is mainly adopted in clinical

4. Vascularized organ 3D printing and vascular transplantation, and the source of donors is
applications greatly restricted. The myocardium, endocardium, and
pericardium are the primary cells that constitute the heart.
2
Clinically, bioartificial vascular grafts should have A high-density capillary network (3000 vessels/mm )
the following characteristics: (i) Excellent blood located in the myocardium functions to regulate the
compatibility with no or a lower risk of thrombosis; (ii) metabolic activity of contraction and works to confine
sufficient mechanical properties and anti-suture strength; the distance between cardiomyocytes and ECs within a
(iii) high-grade biodegradability and tissue restoration range of 2 – 3 μm. Therefore, along with the development
capability; (iv) non-toxicity and no immune rejection of 3D vascularized networks, the replacement of these
with the dissolved, exudated, and degraded products; and cardiovascular tissues using 3D printing technology has
(v) simple preparation method, wide source of materials, been considered as an important issue in the clinical
and low price . perspective. The use of 3D printing technology can
[75]
To simulate and function of the natural organs, easily and quickly produce transplantable blood vessels,
the 3D-printed vascular networks ought to provide including vascular networks.
supplements and oxygen for the tissues and remove the 3D printing heart tissues have been a long-term
cell wastes and carbon dioxide. The robust generation dream for many researchers. Professor Norotte of
of a permeable vascular network is critical for the 3D Columbia University developed a 3D printing technology
printing vascularized organs . 3D printing of a vascular of biogel spheres based on the 3D automatic computer-
[12]
network requires high precision since the limitation of assisted deposition. This technology has repetitive and
cells to capillaries is within 200 μm . Limited by the quantifiable advantages in the printing of non-stents small
[8]
diffusion ability of oxygen and nutrients, the widening diameter blood vessels . Mironov et al. used a modified
[38]
of the distance between cells and capillaries may lead inkjet printer to print a layer of vascular ECs on a layer of
to hypoxia and apoptosis. Under the background of matrix material, forming a quasi-3D structure similar to a
[79]
delayed autophagic digestion of apoptotic debris, further doughnut . A Japanese researcher imitated and modified
aggravation of the necrosis may set up a vicious circle. this process to manufacture the inkjet printers, which
In organ 3D printing, the hierarchical architecture are characterized by fast response speed, high forming
integration of the different parts of the vascular accuracy, high solidification speed, and low viscosity
network is critical. It requires precise geometrical and of forming materials . However, this technology is
[80]
functional control of the building processes, especially still in its infancy due to the defects in mechanical
at the submicron level. In the following section, we strengths, anticoagulant properties, degradation rates, and
mainly introduce the technologies used to construct processability. Leong et al. analyzed the suitable polymers
the 3D vascular networks, including cardiovascular for SLS technology for manufacturing vascular stents .
[81]
systems, vascularized liver tissues, vascularized bones, In 2019, researchers at Tel Aviv University
and vascularized pancreas. The innovation of these announced a breakthrough in heart 3D printing. The

238 International Journal of Bioprinting (2022)–Volume 8, Issue 3