A new biomaterial may help surgeons rebuild the delicate soft structures of the human face, like the cheeks, after a disease or injury has caused disfigurement. The material, which is half synthetic and half biological, can be injected under the skin as a liquid, massaged into shape, and then permanently “locked” by exposure to light.
Soft tissues are hard to replace, especially in the face. “We have metals and plastics for your bone,” says Jennifer Elisseeff, a TR35 winner in 2002 and one of the researchers on a paper published in Science Translational Medicine that describes the work. But surgeons lack good replacements for things like cheeks and lips—and even slight deformities can lead to severe social and emotional problems for patients. Existing implants are often insufficient for reconstructing larger defects, such as those left behind by tumor excisions or extreme trauma.
Alexander Hillel and his colleagues at Johns Hopkins University have created a new type of transplant material that addresses these problems. It’s a blend of hyaluronic acid—a biological material already used as a soft-tissue implant—and polyethylene glycol, a synthetic material. The blend is a liquid polymer that can be injected—thus avoiding the need for surgery. Once injected, the material can be sculpted into the necessary shape. When exposed to light of specific wavelengths, the messy tangle of polymer chains in the liquid implant rearrange into a stable, crosshatched form, stiffening the implant.
The fact that the LED uses visible light to set the implant is important, says Farshid Guilak, a professor of orthopedic surgery and biomedical engineering at Duke University: “Visible light is much safer than UV light, which can have a number of adverse effects, primarily DNA damage and cell death.”
Ali Khademhosseini, an associate professor at Harvard-MIT’s Division of Health Sciences and Technology, says the new material shows great promise. “To my knowledge, this is the furthest that such an approach has been taken, as the paper has extensive animal studies as well as pilot human studies,” he says.
To set the implants, the researchers devised a green-light LED array that can penetrate up to four millimeters of skin. It only takes two minutes of exposure before the implant fully sets, and there were no painful side effects.
To test the implants, researchers injected them into the backs of rats. They then tested several ratios of the hyaluronic acid and polyethylene glycol, examining how long each lasted. The various blends have different levels of elasticity and durability, allowing clinicians to fine-tune the physical properties of an implant for their needs. The longest-lasting implants made it for almost 500 days before being completely resorbed into the rats’ bodies. This means the implants may have to be replaced after a year or so, although Elisseeff hopes that they will act as a scaffolding for new tissue to grow on.
The researchers staged a pilot clinical study in Canada. They injected small implants in the stomachs of three patients scheduled to undergo “tummy tucks.” The implants lasted about 12 weeks, with the only problem being inflammation around the implant. Elisseeff says the inflammation could be a result of irritation caused by the rigidity of the implants, a reaction to the chemicals in the implant, or a by-product of the fat tissue surrounding the implant site. She thinks the problem will be “relatively easy to overcome.”
The next step, says Elisseeff, is a full-scale clinical trial. She’s also working on ways to make soft-tissue implants with minimal synthetic components. “The long view is trying to bring these [tissue engineering] technologies forward to clinical practice,” she says. Although it’s typically taken a long time to get such techniques into use, she’s confident her current work will move to the clinic because “it’s designed to address clinical needs.”
Melissa Knothe Tate, a professor in Case Western University’s Department of Biomedical Engineering, is optimistic. “Getting functional tissue in the right place at the right time has been a major hurdle in the field of tissue engineering,” she says. She adds that this and other recently published technologies could indicate “a new age of regenerative medicine, mimicking the body’s capacity to build new tissue.”
Khademhosseini also finds the results encouraging. “I am hopeful that the paper will yield to a new generation of biomaterials-based applications in soft-tissue replacement,” he says.