Using a sophisticated, custom-designed
3D printer, regenerative medicine scientists at Wake
Forest Baptist Medical Center have proved that it is feasible to print living tissue structures
to replace injured or diseased tissue in patients.
Reporting in Nature Biotechnology, the scientists said they
printed ear, bone and muscle structures. When implanted in animals, the
structures matured into functional tissue and developed a system of blood
vessels. Most importantly, these early results indicate that the structures have
the right size, strength and function for use in humans.
“This novel tissue and organ printer is an important
advance in our quest to make replacement tissue for patients,” said Anthony Atala, M.D., director of
the Wake Forest Institute for Regenerative Medicine (WFIRM) and senior author on the
study. “It can fabricate stable, human-scale tissue of any shape. With further
development, this technology could potentially be used to print living tissue and organ
structures for surgical implantation.”
With funding from the Armed Forces Institute of Regenerative Medicine, a federally funded effort to
apply regenerative medicine to battlefield injuries, Atala’s team aims to
implant bioprinted muscle, cartilage and bone in patients in the future.
Tissue engineering is a
science that aims to grow replacement tissues and organs in the laboratory to help
solve the shortage of donated tissue available for transplants. The precision of 3D printing makes it a promising
method for replicating the body’s complex tissues and organs. However, current
printers based on jetting, extrusion and laser-induced forward transfer cannot produce
structures with sufficient size or strength to implant in the body.
The Integrated Tissue and
Organ Printing System (ITOP), developed over a 10-year period by scientists at the
Institute for Regenerative Medicine, overcomes these challenges. The system deposits
both bio-degradable, plastic-like materials to form the tissue “shape” and water-based
gels that contain the cells. In addition, a strong, temporary outer structure
is formed. The printing process does not harm the cells.
challenge of tissue engineering is ensuring that implanted structures live long
enough to integrate with the body. The Wake Forest Baptist scientists addressed
this in two ways. They optimized the water-based “ink” that holds the cells so that it promotes
cell health and growth and they printed a lattice of micro-channels
throughout the structures. These channels allow nutrients and oxygen from the
body to diffuse into the structures and keep them live while they develop a
system of blood vessels.
It has been previously shown that tissue structures without ready-made
blood vessels must be smaller than 200 microns (0.007 inches) for cells to
survive. In these studies, a baby-sized ear structure (1.5 inches) survived and
showed signs of vascularization at one and two months after implantation.
“Our results indicate that the bio-ink combination we used, combined with
the micro-channels, provides the right environment to keep the cells alive and to
support cell and tissue growth,” said Atala.
Another advantage of the ITOP system is its ability to use data from CT and
MRI scans to “tailor-make” tissue for patients. For a patient missing an ear,
for example, the system could print a matching structure.
Several proof-of-concept experiments
demonstrated the capabilities of ITOP. To show that ITOP can generate
complex 3D structures, printed, human-sized external ears were implanted under the skin of mice. Two months
later, the shape of the implanted ear was well-maintained
and cartilage tissue and blood vessels had formed.
To demonstrate the ITOP can generate organized soft tissue structures, printed
muscle tissue was implanted in rats. After two weeks, tests confirmed that the muscle
was robust enough to maintain its structural
characteristics, become vascularized and induce nerve formation.
And, to show that construction of a human-sized bone structure, jaw bone fragments
were printed using human stem cells. The fragments were the size and shape
needed for facial reconstruction in humans. To study the maturation of
bioprinted bone in the body, printed segments of skull bone were implanted in
rats. After five months, the bioprinted structures had formed
vascularized bone tissue.
Ongoing studies will measure longer-term outcomes.
The research was supported, in part, by grants from the Armed Forces
Institute of Regenerative Medicine (W81XWH-08-2-0032), the Telemedicine and
Advanced Technology Research Center at the U.S. Army Medical Research and
Material Command (W81XWH-07-1-0718) and
the Defense Threat Reduction Agency (N66001-13-C-2027).
are: Hyun-Wook Kang, Ph.D., Sang Jin Lee, Ph.D., Carlos Kengla, B.S., and James
Yoo, M.D., Ph.D., Wake Forest Baptist.