PEG-HA is injected underneath the skin. |
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 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,” says
Jennifer Elisseeff, Ph.D., 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 PEG-HA solution is massaged into the desired shape. |
The
researchers created their composite material from hyaluronic acid (HA),
a natural component in skin of young people that confers elasticity,
and polyethylene glycol (PEG), a synthetic molecule used successfully as
surgical glue in operations and known not to cause severe immune
reactions.
The
PEG can be “cross-linked”or made to form sturdy chemical bonds between
many individual moleculesusing energy from light, which traps the HA
molecules with it. Such cross-linking 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 (MRI)
to monitor the persistence of the implant over time. The implants were
examined at 47 and 110 days with MRIs 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 longor about as wide as a pinky
fingernail. However, the participants said 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 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 ratsbeing different than
human belly fat.
An LED light is used to “crosslink” or lock the material in place. |
“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,”
says Elisseeff.
Elisseeff
said 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, recreating 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 resculpt 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 also of Johns
Hopkins University; Zayna Nahas of Stanford University; Robert Trow and
Andrew Thomas of Energist North America; and Serge Lichtsteiner, Damon
Sutton, Christine Matheson, Patricia Walker and Nathaniel David of
Kythera Biopharmaceuticals.
The research was supported by a grant from Kythera Biopharmaceuticals, which develops cosmetic pharmaceutical products.