Researchers at Carnegie Mellon University and the University of Pittsburgh have successfully directed adult stem cells from mice to develop into bone and muscle cells with the aid of a custom-designed ink-jet printer. They say it’s a first step toward better understanding tissue regeneration, which may one day lead to therapies for repairing damaged tissues, as occurs in osteoarthritis.
For years, tissue engineers have used souped-up printers, and in some cases off-the-shelf models, to print “bio-inks.” These inks consist of anything from proteins to individual cells printed in microscopic patterns. By printing layer upon layer of cell patterns, scientists may one day be able to “print” whole tissues or organs for replacement therapies.
Now Phil Campbell and his team at Carnegie Mellon have added a new branch to the budding field of bioprinting. Certain growth factors spur stem cells to morph into specific kinds of cells, such as bone or muscle. Campbell and his colleagues have successfully printed growth-factor solutions on the same slide, or “paper,” forming a scaffold onto which stem cells can interact and differentiate into bone or muscle cells side by side.
The team loaded its ink-jet printer with a dilute solution containing the growth factor BMP-2, known for turning stem cells into bone cells. Meanwhile, the researchers prepared the paper they would print on: a microscope slide coated with a fibrin matrix–a material found in the body that naturally binds growth factors. The team then printed growth factors one drop at a time, in four separate square patterns of 750 microns. Each square consisted of varying shades, or concentrations, of growth factor, depending on the number of times the researchers printed on top of the same pattern.
Once the slide was dry, researchers placed it in a culture dish and evenly coated it with adult stem cells taken from the leg muscles of mice. Stem cells landing on areas with growth factors began to differentiate into bone cells–the greater the concentration of growth factor, the higher the yield of differentiated bone cells. Stem cells that landed on blank spots turned into muscle cells, which is the default developmental path for these cells.
Campbell’s technique diverges from previous research, in which different types of stem cells are grown individually in separate flasks or incubation vessels. He says that being able to differentiate multiple kinds of cells, such as bone and muscle, side by side mimics the way stem cells naturally differentiate within the body.
“We’re recreating microenvironments that better replicate those that nature normally makes,” says Campbell. “You can envision a scaffold structure where one end promotes bone, one end tendon, the other end muscle. That gives you more control over regenerating that tissue.”