August 29, 2011
New composite material may restore damaged soft tissue
Potential uses include facial reconstruction for soldiers’ blast injuries
Biomedical engineers at Johns Hopkins have developed a new liquid material that in early experiments in rats and humans shows promise in restoring damaged soft tissue relatively safely and durably. The material, a composite of biological and synthetic molecules, is injected under the skin, then “set” using light to form a more solid structure, like using cold to set gelatin in a mold. The researchers say that the product one day could be used to reconstruct soldiers’ faces marred by blast injuries.
The Johns Hopkins researchers caution that the material, described in a report in the July 27 issue of Science Translational Medicine, is “promising” but not yet ready for widespread clinical use.
“Implanted biological materials can mimic the texture of soft tissue but are usually broken down by the body too fast, while synthetic materials tend to be more permanent but can be rejected by the immune system and typically don’t meld well with surrounding natural tissue,” said Jennifer Elisseeff, the Jules Stein Professor of Ophthalmology and director of the Translational Tissue Engineering Center at the Johns Hopkins University School of Medicine. “Our composite material has the best of both worlds, with the biological component enhancing compatibility with the body, and the synthetic component contributing to durability.”
The researchers created their composite material from hyaluronic acid, a natural component in skin of young people that confers elasticity, and polyethylene glycol, a synthetic molecule used successfully as surgical glue in operations and known not to cause severe immune reactions. The polyethylene glycol, or PEG, can be “crosslinked”—or made to form sturdy chemical bonds between many individual molecules—using energy from light, which traps the hyaluronic acid, or HA, molecules with it. Such crosslinking makes the implant hold its shape and not ooze away from the injection site, Elisseeff says.
To develop the best PEG-HA composite with the highest long-term stability, the researchers injected different concentrations of PEG and HA under the skin and into the back muscle of rats, shone a green LED light on them to “gel” the material and used magnetic resonance imaging to monitor the persistence of the implant over time. The implants were examined with MRIs at 47 days and 110 days and removed. Direct measurements and MRIs of the implants showed that the ones created from HA and the highest-tested concentration of PEG with HA stayed put and were the same size over time compared to injections of only HA, which shrank over time.
The researchers evaluated the safety and persistence of the PEG-HA implants with a 12-week experiment in three volunteers already undergoing abdominoplasty, or “tummy tucks.” Technicians injected about five drops of PEG-HA or HA alone under the belly skin. None of the participants experienced hospitalization, disability or death directly related to the implant, which was about 8 mm long, about as wide as a pinky fingernail. However, the participants said that they sensed heat and pain during the gel-setting process. Twelve weeks after implantation, MRI revealed no loss of implant size in patients. Removal of the implants and inspection of the surrounding tissue revealed mild to moderate inflammation due to the presence of certain types of white blood cells. The researchers said that the same inflammatory response was seen in rats, although the types of white blood cells responding to implant differed between the rodents and humans, a difference the researchers attribute to the back muscles—the target tissue in the rats—being different from human belly fat.
“We still have to evaluate the persistence and safety of our material in other types of human tissues, like muscle or less-fatty regions under the skin of the face, so we can optimize it for specific procedures,” Elisseeff said.
Elisseeff said that the team has especially high hopes for the composite’s use in people with facial deformities, who endure social and psychological trauma. When rebuilding soft tissue, re-creating natural shape often requires multiple surgeries and can result in scarring. “Many of the skin fillers available on the market consisting of HA-like materials used for face lifts are only temporarily effective and are limited in their ability to re-sculpt entire areas of the face. Our hope is to develop a more-effective product for people, like our war veterans, who need extensive facial reconstruction. ”
Other researchers involved in the study are Alexander Hillel, Shimon Unterman, Branden Reid, Jeannine Coburn, Joyce Axelman, Jemin Chae, Qiongyu Guo, Zhipeng Hou, Susumu Mori and Janis Taube, all of Johns Hopkins; Zayna Nahas, of Stanford University; Robert Trow and Andrew Thomas, both of Energist North America; and Serge Lichtsteiner, Damon Sutton, Christine Matheson, Patricia Walker and Nathaniel David, all of Kythera Biopharmaceuticals.
The research was supported by a grant from Kythera Biopharmaceuticals, which develops cosmetic pharmaceutical products.