The research has been featured on the cover
page of this week's issue of
, a journal
published by the American Association for the Advancement of Science (AAAS).
The cover photo depicts a bioengineered hydrogel model of a lung air sac or
alveolus that delivers oxygen to the body.
The study was led by Dr. Jordan S. Miller,
Ph.D. and Dr. Kelly Stevens, Ph.D. Dr. Miller is an Assistant Professor in the
Department of Bioengineering at the George R. Brown School of Engineering, Rice
University, Houston, Texas, USA. Dr. Stevens is an Assistant Professor in the
Department of Bioengineering at the University of Washington, Seattle,
The study was conducted in collaboration with
Duke University, Durham, North Carolina, Rowan University, Glassboro, New
Jersey, and Nervous System, a generative design studio in Somerville,
"One of the
biggest roadblocks to generating functional tissue replacements has been our
inability to print the complex vasculature that can supply nutrients to densely
said Miller. "Further,
our organs actually contain independent vascular networks - like the airways
and blood vessels of the lung or the bile ducts and blood vessels in the liver.
These interpenetrating networks are physically and biochemically entangled, and
the architecture itself is intimately related to tissue function. Ours is the
first bioprinting technology that addresses the challenge of
multivascularization in a direct and comprehensive way."
In this regard,
Stevens indicated that multivascularization is important because structure and
function are always interrelated."Tissue
engineering has struggled with this for a generation,"
Stevens said. "With this work, we can now better ask, 'If
we can print tissues that look and now even breathe more like the healthy
tissues in our bodies, will they also then functionally behave more like those
tissues?' This is an important question, because how well a bioprinted tissue
functions will affect how successful it will be as a therapy."
Why is Bioprinting So Important?
Bioprinting is a very powerful technology
that can be used to print human tissues and organs. Since there is an
ever-increasing demand for human organ transplantation
power of this robust technique can be harnessed to create bioprinted organs
that could, one day, reduce the reliance on natural human organs for
transplantation. Moreover, transplantation of bioprinted organs will alleviate the
need for lifelong treatment with immunosuppressants, which is currently the
norm. In fact, the researchers are optimistic that the application of
bioprinting in medicine could become a reality within the next two decades.
How were the Bioprinted Organs Fabricated?
The research team
bioprinted the intricate components of the human liver and lungs using a new
open-source bioprinting technology called Stereolithography
Apparatus for Tissue Engineering (SLATE)
. This technology utilizes additive
manufacturing for making soft hydrogels that are constructed layer-by-layer.
Each layer is printed
using a liquid pre-hydrogel solution that solidifies upon exposure to the blue
light generated by a digital light projector. Each of the layers, which are
roughly 10-50 microns in thickness, is sequentially added on top of each other
to create the 3D structure of the tissue or organ.
This technique allows
the production of soft, water-based, biocompatible gels that can be moulded
into intricate internal structures of organs within a matter of minutes. In
this regard, the bioengineers from Nervous System were instrumental in
designing the internal architecture of the tissues and organs.
What did Bioprinted Organ Testing Reveal?
Tests were carried
out on bioprinted lung alveoli and liver tissue, which are indicated below:
- Lung Alveoli: The tests
revealed that the lung-mimicking air sacs (alveoli) were stable and capable of
carrying air without bursting. Since these alveolar sacs were pulsatile, they
allowed the rhythmic flow of air that closely resembled human breathing. The
tests also revealed that the red blood cells were capable of taking up oxygen
during their passage through the network of blood vessels that surrounded the
alveolar sacs. Importantly, the movement of oxygen closely resembled the gas
exchange that occurs in the actual lung alveoli.
- Liver Tissue: In case of liver
tissue, tests were carried out in vivo
in a mouse model of chronic liver disease. The 3D printed liver tissues, which
had separate compartments for blood vessels and liver cells, were loaded with
primary hepatocytes and implanted into mice. The tests revealed that the liver
cells survived the implantation process
Future Prospects of Bioprinting Technology
The newly developed
bioprinting technology has tremendous prospects in the medical field. The
technology can be applied for developing structures such as bicuspid valves
present in the heart, which allows blood to flow only in one direction. Other
types of valves present within the leg veins, and associated lymphatic vessels
can also be printed using this technology. Thus, bioprinting these
multivascular and intravascular structures introduce extensive design freedoms
for engineering living tissues, which makes it possible to build a great
variety of intricate structures present in the human body.
The new bioprinting
technology is currently being commercialized through a start-up company called
Volumetric. This Houston-based company designs and manufactures bioprinters and
Since an open-source
model was used for developing the 3D bioprinting technology, all data are
freely available in the public domain for use by anyone wanting to build their
own stereolithography printing apparatus and hydrogels.
In this regard,
Miller said: "Making the hydrogel design
files available will allow others to explore our efforts here, even if they
utilize some future 3D printing technology that doesn't exist today."
added: "We are only at the beginning of
our exploration of the architectures found in the human body and still have so
much more to learn."
The study was funded by the National Institutes of
Health (NIH), the National Science Foundation, the Robert J. Kleberg, Jr. and
Helen C. Kleberg Foundation, the John H. Tietze Foundation, and the Gulf Coast
- Multivascular Networks and Functional Intravascular Topologies within Biocompatible Hydrogels - (https://science.sciencemag.org/content/364/6439/458)