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10137 이수안
10137 이수안
Myocardium Bioprinting
International
Leader: Sooan Lee (10137)
Member: SeokWon Jung (10142)
Ⅰ. Abstract
Despite the high demand for cardiac organs, insufficient supply caused millions to
die due to cardiovascular diseases (CVD), cardiomyopathy, and coronary artery disease
(CAD) every year. Modern medicine has developed technologies to 3D print organoids that
effectively resemble the cardiac organ which might be a breakthrough in curing cardio-
cells, proteins, hydrogels, and other biomaterials. In the process of manufacturing cardiac
organoids, cultivating the myocardium itself is critical. We will explain the biological and
chemical process of inducing natural fibroblasts into pluripotent stem cells (PSCs) and
9) enzymes interfere with the polymerase process, iPSC modifies a certain part of the
histone protein which activates gene transcription. When we get to the cardiomyocyte
Ⅱ. Introduction
Starting from the 1980s and being popularized in 2009, bioprinting has been around for
quite some time. From printing photosensitive resin layer by layer to printing stem cells on
collagen bases, this field has progressed to develop correlation and accuracy day by day. There
are three 3D printing methods developed so far, each has its own pros and cons. The materials
used in these printers have also developed to a point where the cells are just identical, and with
Diving into the mechanisms of iPSC and histone methylation, here’s the flow. Before iPSCs are
ready to be modified by transcription factors in the transcription start site (TSS), they go
modification. After the transcription factors bind the gene expressions, additional protein kinase
is necessary to regulate tissue-specific genes. This protein interacts with the Extra Cellular
Matrix (ECM) to reinforce cardiomyocytes to proliferate and attenuate CVDs along with other
cardiac diseases.
Ⅲ. Bioprinting
1. About Bioprinting
capable of producing living parts such as tissues, blood vessels, bones, and in further
potential, organs. Bioprinting requires an appropriate bioink to operate. Bio ink consists
of biomaterials such as living cells, proteins, nanomaterials, and other bioactive agents.
cellular materials (or dECM) used in bioink should satisfy several requirements to
compose a bioink. Those non-cellular materials should dissolve in a real body and
2. Types of Bioprinting
nozzle dispenses the droplets of dilute and precise bioink solution without contact.
reaches the capability of producing “real–like” organs, bioprinted organs would serve
as the alternative to animal testing. Instead of testing animals for new drug research,
testing bioprinted organs would be more ethical and beneficial. Using bioprinted organs
also leads to higher effectiveness and accuracy in testing since the test subject
(bioprinted organ) shows higher similarity to actual human organs. Bioprinted organs
are also open to the possibility of more accurate and personalized (or patient-specific)
cures. If the bioink contains the patient’s own living cells, proteins, and other
biomaterials, the bioprinted organ would react similarly to the patient’s actual organ,
thus ending up with minimizing side effects and maximizing the effectiveness of the
to the Life Source, “Each day, 17 people die waiting for a life-saving organ transplant
and a new name is added to the transplant waiting list every 9 minutes.” As can be
inferred, an organ for transplant has a high demand but a relatively less supply, thus
ending up in the loss of so many lives. The main reason why it is so hard to get an
requirements such as the size, blood type, et cetera. However, if bioprinted organs
artificial organ to the patient. This process also involves the patient’s own cells and
Ⅳ. Myocardium Bioprinting
Myocardium is a specialized muscle tissue that forms the muscle of the heart. It is the
middle layer of the four heart walls in each heart chamber. The heart muscle tissues
including myocardium are responsible for keeping the heart pumping blood by
involuntarily contracting and releasing. Therefore, the myocardium plays a vital role in
cardiac functions, and thus myocardial diseases are extremely problematic since it is
intimately associated with cardiac dysfunction. The primary cause of most cardiac
phenomenon that occurs when the plaques(atherosclerosis) block the coronary artery
and gradually narrow the artery, disabling the blood and oxygen supply. When the
blood is not regularly supplied, the cardiomyocytes (cells responsible for the
contraction of the heart), and even the whole tissue, are destroyed. Once the
cardiomyocytes and the tissue are destroyed, the heart cannot contract, ultimately
infarction. These diseases result in the loss of the ability to pump and circulate blood
The obstruction of a coronary artery can be resolved by stents (a medical procedure that
enlarges the blood vessels). However, the destroyed myocardial tissue needs to be
replaced by new healthy tissue since the heart does not regenerate the cardiomyocytes.
This is when the bioprinted myocardium is needed. The bioprinted myocardium will
replace the destroyed natural myocardium, helping the heart to recover its original
Ⅴ. Cardiomyocyte Mechanism
1. Myocardium modeling through iPSC
methylation.
the key factor in maintaining the differentiation pluripotency of embryonic stem cells.
Its modification enriches in cis-regulatory regions of the transcriptional start sites (TSSs).
Before RNA Polymerization II, these epigenetic modifiers rearrange the chromatin from a
P300/CBP stage. Fourth, OSKM iPSC transcription factors start binding proteins to control
gene expression.
2. Cardiomyocyte Proliferation
specific gene regulation is identified, in this case, Glycogen synthase kinase 3(GSK-3)
GSK-3 protein kinase phosphorylates glycogen synthase and activates enzymes that
signaling. As a result, GSK-3 interacts with the extracellular matrix (ECM) while
with highly advanced technologies such as iPSC. It is therefore predictable that myocardium
bioprinting would lead the cardiology field and ultimately benefit many patients suffering from
cardiac diseases and desperately waiting for the transplant. However, there are still limitations in
creating a real-like artificial cardiac muscle tissue. Prevalent limitations in the current state are
immunogenicity (the ability of a foreign substance to provoke an immune response in the body),
make an alternative to the natural dysfunction of cardiac muscle tissue, the adverse reaction and
the construction of the microenvironment are also significant factors to be considered. Research
limitations of the current state and step out further to reach greater achievements that would
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