Bioprinting, Part 1: The Promise and the Pitfalls
Mar 26, 2014 6:26 AM PT
It's long been the dream of humans to be able to regenerate body parts. Scientists have been researching this possibility for years, but the subject is complex, and they are just beginning to get to a glimmer of understanding as to what's required.
"There are different layers of complexity in developing tissue-engineered products, so the easiest thing is to make it something that's one single type of cell and is a flat sheet," Charlie Whelan, healthcare and life science director of consulting at Frost & Sullivan, told TechNewsWorld.
Hospitals do grow single sheets of epithelial cells for use in patching burns and wounds or to wrap around organs, but that's a far cry from human skin, which is "multilayer, complex, has different types of cells, and is vascular," Whelan continued.
Step Aside, Gutenberg
In the meantime, the advent of 3D printers has opened up fresh possibilities.
Researchers at Edinburgh's Herriott-Watt University reportedly have invented a printer that creates living embryonic cells, according to LiveScience.
Researchers in China's Hangzhou Dianzi University claim to have developed a biomaterial 3D printer they call "Regenovo" that they say can print out small amounts of human tissues.
The U.S. National Aeronautics and Space Administration last year awarded US$100,000 for research into 3D printing of biomaterials.
All the Organs That Are Fit to Print
Many of the companies offering 3D biomaterial printers restrict themselves to printing out dental materials and bones.
Regenhu goes further. Its line of BioInk biomaterials can be used with its BioFactory bioprinters to create 3D constructs of cells and proteins, and complex models of organs for automated in-vitro assays for clinical diagnostics and drug discovery, and to create in-vitro models of human diseases.
The idea is to conduct biochemical tests on 3D tissues printed from a patient's own cells rather than on the patient, explained Jordan Miller, assistant professor of bioengineering at Rice University. "Right now, animal models can't fully predict drug toxicity and function in humans."
3D printing of skin will be readily translated to clinical use, but "3D printing of other tissues may take longer for clinical and commercial translation due to the fact that many other tissues have more complex structures," Roger Narayan, Ph.D., M.D., a professor in the joint biomedical engineering department at North Carolina State University and the University of North Carolina at Chapel Hill, told TechNewsWorld.
Narayan led a team from both universities and Laser Zentrum Hannover in research that discovered Vitamin B2, or riboflavin, can be used in 3D printing to create nontoxic medical implants.
Hope for the Hurt
Nearly 2 million people in the U.S. have lost at least one limb, according to the Amputee Coalition. About 185,000 amputations are conducted in the U.S. each year. Rejection of transplanted organs is the main problem for patients undergoing this procedure.
Bioengineered tissues may reduce the danger of tissue rejection following surgery, offer a higher rate of healing, and improve patients' chances of survival, Narayan said.
"The Department of Defense has committed significant resources over the years to the use of tissue engineering for treatment of traumatic injuries," Narayan continued. "3D printing-based and other tissue-engineering technologies will have a high impact on the treatment of traumatic injuries, as well as tissue loss associated with cancer and tissue degeneration."
The Blood Is the Life
Providing bioprinted organs a network of blood vessels so they can thrive has proved to be a major problem.
"Everyone in our field is trying to solve the vascularization challenge," Rice University's Miller told TechNewsWorld.
What about Regenovo, then?
"I would ... caution [against] taking the Regenovo report too far, and I wouldn't consider it all done," Miller remarked. "They admit they are still 10-20 years away from [developing] whole organs."
Other Issues With Bioprinting
The technical side of printing small-volume organs "may be achieved within the next two years," Kevin Healy, chair of the department of bioengineering at the University of California at Berkeley, told TechNewsWorld. However, the ability to develop vascularization of such organs is at least five years away.
"The harder problem is to figure out what cells to use to avoid immune rejection," Healy continued.
Once this has been solved, researchers have to get donor cells and learn how to differentiate donor stem cells to the appropriate cells for the specific organ being printed.
"We know how to do this for a number of cell types, but, for a number of other cells like hepatocytes (liver cells), this is much more difficult," Healy pointed out.
Then there is the problem of nerve regeneration. Bioengineered products will require nerves, but "nerve regeneration is more difficult than blood vessel, soft tissue or hard tissue regeneration," Narayan said.
A Long Time A-Coming
"Parts of the body which require human cells to perform biomechanical functions, such as the liver or kidney, are still several decades away from reaching human patients," Miller said. "We are still in the feasibility stage -- not sure how to keep cells alive at high cell density and adequate size needed to match human organs."
A 3D structure will require nearly 1 billion functioning cells to approximate the function of a liver or kidney, and "there are dozens of cell types in these organs," Miller pointed out. "We are typically only looking at one or two cell types being put into a 3D printed structure."
It takes some time to grow enough cells from a biopsy to build something the size of a human organ, so the prospect of treating acute injuries with 3D printing is currently remote, Miller said. However, some researchers are looking at 3D printing a patient's cells and tissue directly into a wound in the operating room, though this would require having a "large stock" of these cells available in deep freeze.
Regeneration Is a No-Grow Zone
As for the dream of human limb and organ regeneration, forget about it.
"The cascade of signals and gene regulation which lets a newt regrow an entire limb was recently shown to not be present in the human genome," Miller observed. "So, for human limb replacements, we are probably going to need to think about reconstruction rather than stimulation of regrowth."