Any fan of Star Trek knows that simply shining light on an injury will heal many wounds in the future. Now scientists have brought that future a bit closer. In a new study, researchers have found a way to stimulate the growth of blood vessels—an important part of healing—by hitting the skin with ultraviolet light.
In the past decade, scientists have used light to manipulate the chemistry of cells in a dish—but they’ve struggled to do the same in living organisms. “There are hundreds of different types of cells; you have a lot more other biological molecules present,” says bioengineer Andrés García of the Georgia Institute of Technology in Atlanta.
So García and colleagues turned to a water-based gel, or hydrogel, impregnated with a molecule called RGD peptide. The body uses this peptide to signal cells to stick to and grow on new tissues. The team then attached another molecule to the RGD peptide to shut it down. When the researchers shone UV light on the hydrogel, this molecular disguise dropped off and the RGD peptide became active.
The scientists then moved to animal experiments. They made cuts on the backs of mice and implanted samples of the hydrogel underneath their skins. They exposed some samples of hydrogel to UV light immediately after implantation, and they exposed others either 7 or 14 days later.
Cells grew just as well around the peptide-impregnated samples, irrespective of when they were irradiated, the team reports online this week in Nature Materials. When the RGD peptide was activated immediately after implantation, the mouse's immune system recognized it as a foreign body and surrounded the hydrogel with scar tissue. When the peptide was left dormant for a few days before activation, however, the body's immune response was much weaker and the hydrogel became better integrated into the mouse's tissue.
The researchers then implanted samples of hydrogel that, along with the RGD peptide, had also been impregnated with a protein called vascular endothelial growth factor that stimulates the growth of new blood vessels. Normal samples of hydrogel sparked the growth of few blood vessels when implanted into the mice. But samples that had been impregnated with vascular endothelial growth factor and RGD ahead of time and then exposed to UV light after implantation had become interlaced with networks of blood vessels, allowing the mouse's own blood supply to send blood through the hydrogel. This is important, García explains, because if tissue grown in the lab is implanted into the body, it won't stay alive for very long unless it is fed with nutrients by the animal’s own blood supply.
One problem with the approach is that to dislodge the blocking group and activate the RGD peptide, the researchers had to use UV light, which does not penetrate very deep into skin—90% of the light was absorbed by just the top 0.5 mm of mouse skin. The 10% that got through was still able to activate all the peptide. Although the process might be good enough in mice, it would have limited use in humans, who have much thicker skin. The researchers are now trying to develop a process that will work with infrared light, which penetrates human tissue much better. In principle, infrared light is also safer, as UV light can damage the skin and cause cancer (which is why you need sunscreen on the beach), although the brief (10-minute) UV exposures used here did not cause any apparent damage to the mice's skins.
“It's very exciting,” says stem cell bioengineer Matthias Lütolf of the Swiss Federal Institute of Technology in Lausanne. “It's the first demonstration that this concept of really controlling biomaterials' properties in space and time by light can be made to work in vivo.” He cautions, however, that although this study provided an important proof of principle, the researchers here simply stimulated blood vessels to grow at a time of their choosing—they would still have grown if they had never caged the RGD peptide in the first place. The next step, he says, is to demonstrate that, by controlling the time at which they turn a molecular signal on, the researchers can make a process happen that wouldn't happen otherwise. “Everything that's large in the human body is difficult to repair,” he says, “because you very quickly get scar formation. Now I wonder: Can we block scar tissue formation and inflammation and at some point release a signal that then allows the healing?”
Fellow bioengineer Jennifer Elisseeff of Johns Hopkins University in Baltimore, Maryland, also finds the research promising. She says that, even with the limited penetration of UV light, the technology may already have uses. The ability to trigger the growth of blood vessels into an implant while minimizing the body's inflammatory response, she says, could be used to produce glucose sensors that could be implanted directly into the bodies of diabetics and left there, continuously monitoring the sugar content of the blood flowing through them. More generally, she says, “this opens a door for really being able to manipulate the interactions of the body with these types of implants. I think we'll start understanding how primitive we really were.”