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Soman and Vijayavenkataraman
size, pore geometry, and the surface contact area
are the deciding factors for successful growth of
functional ovarian tissue. Stem cells isolated from
the patient’s own ovarian tissue can serve as the
starting material to bioprint the functional ovary.
4.2.3 Thyroid gland replacement in
thyrectomized patients
Bioprinting of a functional vascularized mouse
thyroid gland construct from embryonic tissue
spheroids was reported by Bulenova et al. in
2017 [103] . Self-assembling thyroid spheres,
thyrocytes, and endothelial cells suspended in
collagen gel were used for bioprinting the thyroid
gland. The bioprinted construct was implanted in
a hypothyroid mouse and it could normalize the
blood thyroxine levels and body temperature in
the tested mice. Bioprinting of functional mouse
thyroid gland tissue represents a major advance
in bioprinting technology and organ regeneration
research. In March 2019, NASA announced a
plan for bioprinting thyroid gland in international
space station to study the effect of microgravity on
organs [104] .
4.3 Bioprinted iPSCs in disease modeling
The most advantageous aspect of using induced
pluripotent cells in clinics is the ability of
reprogramming of autologous cells taken directly
from patients. At present, the majority of disease
modeling studies makes use of the traditional
2D cultures. Any monogenic or polygenic
disease conditions can be re-created in a cell
culture system [83] . While 2D cultures are good
to understand the molecular level interactions,
they possess several limitations including lack
of heterogenic cell environment and the cell
to cell communication cues [105] . The disease
progression hugely depends on the extracellular
matrix (ECM) mechanics and the cell to cell
interactions [106] . Cellular phenotypes and the
non-cell autonomous disease pathogenesis
require mimicking the disease conditions in
a more realistic 3D environment. 3D disease
models would help in understanding the disease
mechanism in detail in the early stages of
International Journal of Bioprinting (2020)–Volume 6, Issue 4
the disease [107,108] . A few examples of disease
modeling in cardiac, neurodegenerative and
neurodevelopmental diseases and oncology are
briefly discussed in the following sections.
4.3.1 Cardiac diseases
Cardiovascular diseases remain the leading cause
of death in the developed world, accounting for
more than 30% of all deaths. Collection of cardiac
tissue from patients with disease causing mutations
for genetic studies and functional analyses is a
highly invasive procedure. iPSCs derived from the
peripheral tissues of patients with disease specific
mutations are a valuable tool to study the cardiac
pathophysiology and drug development. Cardiac
tissues were biofabricated using hydrogels
and supporting cells such as cardiomyocytes,
endothelial cells, smooth muscle cells, and
fibroblasts [109,110] . The cells were cocultured and
engineered to resemble their natural physiological
microenvironment and recapitulate coordinated
contractile and electrophysiological interactions
with the ECM and heterogeneous cell types that
make up the myocardial tissue environment [111] .
The iPSC-derived cardiac cells were successfully
used to model cardiac diseases such as dilated
cardiomyopathy and myocardial infarction [112] .
These disease models help identifying the cellular
phenotypes critical to cardiac pathology [113,114] .
The microfluidic organ-on-chip methods were
also developed to evaluate the vascular perfusion
in cardiac tissue. The tissue composition and
architecture of the in vitro 3D microdevice can
be precisely defined using microfabrication
[115-117]
methods . The iPSC and embryonic stem
cell derived organ-on-chip systems are being used
for modeling a wide range of diseases, including
dilated cardiomyopathy, kidney glomerular injury,
[118,119]
and wound healing .
4.3.2 Neurodegenerative and
neurodevelopmental diseases
4.3.2.1 Alzheimer’s disease (AD)
AD is a progressive neurodegenerative disorder
characterized by loss of cognition and disruption
of basic functions, such as swallowing, walking,
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