Human tissue engineering might sound like a fictional concept straight out of a sci-fi novel, but it’s for real.
UC San Diego professor and researcher Shaochen Chen is developing 3-D printing methods that will one day manufacture new organs for implantation. His “bioprinting” technology starts with biocompatible liquid polymers mixed with stem cells and other biological materials. When precisely controlled light strikes these liquids, they are transformed into 3-D live structures with nanoscale details.
At first, these bioprinted tissues will be used mainly for testing pharmaceuticals. But the potential of the technology is nothing short of staggering: Chen and other researchers have already 3-D-printed an artificial cornea, blood vessels and a device that cleans the blood just like a liver.
A nanoengineering professor at the UC San Diego Jacobs School of Engineering, Chen is a founding co-director of the university's Biomaterials and Tissue Engineering Center and also a faculty member at the Institute of Engineering in Medicine. The shared mission of these two entities is to translate research on the cutting edge of the biological sciences into real-world clinical applications.
To make tissue, Chen and fellow researchers first had to create a device that would construct the tissue. That’s where 3-D printing technology comes in.
The future — in 3-D
Three-dimensional printing is already being used in healthcare to make, for instance, prosthetic limbs and dental fixtures. But this technology isn’t sophisticated enough to work on the minute scale needed to replicate tissues made of living cells.
“There are two main issues with such technology,” Chen said. “Slow speed, since it is done drop-by-drop, and limited printing resolution not capable of printing nanoscale structures.”
Biological cells communicate with their environments at a nanoscale. So to create tissue, it was critical to develop printing technology that could build structures to interact with microenvironments.
The 3-D printer developed in Chen’s lab uses light to turn biocompatible liquids mixed with cells into solid structures, these light beams quickly placing many thin hydrogel layers on top of one another.
“The light pattern is designed such that we can create 3-D constructs layer-by-layer,” Chen said. “We can control the light pattern in a nanometer scale. That allows us to create nanometer 3-D structures.
“Although cells are several microns in size, they ‘see’ and ‘feel’ and therefore communicate with their surrounding environment at a nanoscale. Using light for 3-D printing also allows us to print 3-D structures in a rapid fashion (merely seconds). This is important so that cells can survive better during the printing time.”
A team effort
Collaboration is key in 3-D bioprinting, requiring expertise in engineering, biomaterials science, cell biology, physics and medicine. “The significant biological questions and medical needs usually come from our collaborators in medicine and biology before we print real tissue,” Chen said.
One of his collaborators is Kang Zhang, a professor of ophthalmology and chief of ophthalmic genetics at UC San Diego. Zhang's lab provided the stem cells, human clinical materials and animal models which the team used to 3-D-print an artificial cornea.
“This will make us independent of human cornea donor tissues,” said Zhang, looking at the future application of bioprinting in ophthalmology. “It has been so exciting to work together to transform medicine.”
Other milestones reached by Chen and his collaborators include 3-D printing of blood vessels, as well as the development of a liver-like device that Chen says is capable of safely detoxifying blood.
Like a dialysis machine, the artificial liver is used externally. Nanoparticles are used to sense, attract, trap and neutralize toxins that can damage cell membranes. Chen estimates the device will be ready for testing on people in a couple of years.
Chen’s work in nanoscale bioprinting is possible through a four-year, $1.5-million grant from the National Institutes of Health. In February he was awarded an additional $1.4 million in funding from the California Institute for Regenerative Medicine for development of 3-D bioprinting techniques using human embryonic stem cell-derived heart muscle cells to create new cardiac tissue.
Chen and colleagues are exploring the possibility of engineering healthy cardiac tissues bioprinted from heart muscle cells that could then be implanted in a damaged heart, restoring function.
“3-D printing and bioprinting will be an enabling technology to realize precision medicine,” Chen said. “It can print patient-specific tissue or organs to tailor treatments for different people.”
—Julia Clerk, Brand Publishing Writer