SAN DIEGO — Someday, perhaps, printers will revolutionize the world of medicine, churning out hearts, livers and other organs to ease transplantation shortages. For now, though, Darryl DLima would settle for a little bit of knee cartilage.
DLima, who heads an orthopedic research lab at the Scripps Clinic here, has made bioartificial cartilage in cow tissue, modifying an old inkjet printer to put down layer after layer of a gel containing living cells. He has also printed cartilage in tissue removed from patients who have undergone knee replacement surgery.
There is much work to do to perfect the process, get regulatory approvals and conduct clinical trials, but his eventual goal sounds like something from science fiction: to have a printer in the operating room that could custom-print new cartilage directly in the body to repair or replace tissue that is missing because of injury or arthritis.
Just as 3-D printers have gained in popularity among hobbyists and companies who use them to create everyday objects, prototypes and spare parts (and even a crude gun), there has been a rise in interest in using similar technology in medicine. Instead of the plastics or powders used in conventional 3-D printers to build an object layer by layer, bioprinters print cells, usually in a liquid or gel. The goal isnt to create a widget or a toy, but to assemble living tissue.
At labs around the world, researchers have been experimenting with bioprinting, first just to see whether it was possible to push cells through a printhead without killing them (in most cases it is), and then trying to make cartilage, bone, skin, blood vessels, small bits of liver and other tissues. There are other ways to try to engineer tissue one involves creating a scaffold out of plastics or other materials and adding cells to it. In theory, at least, a bioprinter has advantages in that it can control the placement of cells and other components to mimic natural structures.
But just as the claims made for 3-D printing technology sometimes exceed the reality, the field of bioprinting has seen its share of hype. News releases, TED talks and news reports often imply that the age of print-on-demand organs is just around the corner.
The reality is that, although bioprinting researchers have made great strides, there are many formidable obstacles to overcome.
Nobody who has any credibility claims they can print organs, or believes in their heart of hearts that that will happen in the next 20 years, said Brian Derby, a researcher at the University of Manchester in Britain who reviewed the field last year in an article in the journal Science.
For now, researchers have set their sights lower. Organovo, for instance, a San Diego company that has developed a bioprinter, is making strips of liver tissue, about 20 cells thick, that it says could be used to test drugs under development.
A lab at the Hannover Medical School in Germany is one of several experimenting with 3-D printing of skin cells; another German lab has printed sheets of heart cells that might someday be used as patches to help repair damage from heart attacks. A researcher at the University of Texas at El Paso, Thomas Boland, has developed a method to print fat tissue that may someday be used to create small implants for women who have had breast lumpectomies.
Boland has also done much of the basic research on bioprinting technologies. I think it is the future for regenerative medicine, he said.
Cartilage could be simpler
DLima acknowledges that his dream of a cartilage printer perhaps a printhead attached to a robotic arm for precise positioning is years away. But he thinks the project has more chance of becoming reality than some others.
One reason, he said, is that cartilage is in some ways simpler than other tissues. Cells called chondrocytes sit in a matrix of fibrous collagens and other compounds secreted by the cells. As cells go, chondrocytes are relatively low maintenance they do not need much nourishment, which simplifies the printing process.
Keeping printed tissue nourished, and thus alive, is one of the most difficult challenges facing researchers. Most cells need to be within a short distance usually a couple of cell widths of a source of nutrients. Nature accomplishes this through a network of microscopic blood vessels, or capillaries.
But trying to emulate capillaries in bioprinted tissue is difficult. With his fat tissue, Bolands approach is to build channels into the degradable gel containing the fat cells, and line the channels with the kind of cells found in blood vessels. When the printed fat is implanted, the tubes start to behave as micro blood vessels, he said.
With cartilage, DLima does not need to worry about blood vessels the chondrocytes get the little nourishment they need through diffusion of nutrients from the joint lining and bone, which is aided by compression of the cartilage as the joints move. Nor does he need to be concerned with nerves, as cartilage lacks them.
But there is still plenty to worry about. Although it is less than a quarter of an inch thick, cartilage of the type found in the knee or hip has a complex structure, with several layers in which collagen and other fibrous materials are oriented differently.
The printing demands change with every layer, DLima said. Most 3-D printers just change the shape. We are changing the shape, the composition, the type of cells, even the orientation of the cells.
Plenty of challenges
DLima has been involved in orthopedic research for years; one of his earlier projects, a sensor-laden knee-replacement prosthesis called the electronic knee, has provided invaluable data about the forces that act on the joint. So he was aware of other efforts to make and repair cartilage.
But we didnt want to grow tissue in the lab and then figure how to transplant it into the body, he said. We wanted to print it directly in the body itself.
He and his colleagues began thinking about using a thermal inkjet printer. The technology is very reliable and is used in most consumer printers, but the researchers were wary because of the heat produced. We thought it would kill the cells, DLima said.
But Boland, then at Clemson University, and others had done the basic research that showed that the heat pulse was so rapid that most cells survived the process.
There are plenty of other challenges as well, DLima said, including a basic one: how to get the right kinds of cells, and enough of them, for the printer. It would not make much sense to use a patients own limited number of cartilage cells from elsewhere in the body. So his lab is investigating the use of stem cells, precursor cells that can become chondrocytes.
The advantage of stem cells is that it would mean a virtually unlimited supply, DLima said.
DLima said the biggest remaining hurdles were probably regulatory ones including proving to the FDA that printed cartilage can be safe and that most of the scientific challenges had been met.
I think in terms of getting it to work, we are cautiously optimistic, he said.