Botox

Facial plastic surgeon Dr. Patrick Byrne gives Botox injections to patient Sandy Rosenblatt of Sterling, Va. (Barbara Haddock Taylor, Baltimore Sun / September 21, 2011)

When Sandy Rosenblatt looked in the mirror, the striking brunette could see nothing but one big flaw — her eyes, which were sunken and seemed a little dark. So at 34 she had a plastic surgeon smooth them over. While she was there, she decided to have her long oval face made a little cheekier and her brows a little less creased.

Since then the Sterling, Va., resident has had to return to her doctor in Baltimore several times a year for new applications of commercial fillers and wrinkle removers, a drawback of such products.

But a biomedical engineer at Johns Hopkins is experimenting with a new material that is part biological, like the fillers, and part synthetic, like implants used in bigger facial reconstruction jobs. The liquid can be injected under the skin, molded into just about any facial feature and locked into place with the energy of a light.

This new substance, called a photo-activated composite biomaterial, has the potential to become the most long-lasting, and versatile, of products used on people like Rosenblatt, as well as those born with defects or who suffer trauma and need a whole new face.

"There are soldiers suffering blast injuries and people who face plant on their bikes, and they just want to look like they did," said Jennifer Elisseeff, the Hopkins researcher who has lead a team working on the new substance for three years. "On the cosmetic side, people want to look like they did 10 years ago. Now, what's available is so limited."

There are no guarantees that this will be approved for use in doctors' offices, but Elisseeff and others watching her progress say the research is extremely promising. It could mean trips to the doctor for touch-ups every few years instead of every few months — a convenience and potential money-saver, though it's too soon to say how much it might cost.

Rosenblatt's doctor says it's the kind of product he's been waiting for. Dr. Patrick J. Byrne, director of facial plastic and reconstructive surgery at Hopkins, says existing products are restrictive, especially for those in need of extensive reconstruction.

Those patients typically need many surgeries, which come with potential complications such as bleeding, nerve damage and infection.

"This is a bit of a holy grail," said Byrne, also an associate professor in Hopkins departments of otolaryngology, head and neck surgery and dermatology. "There have been countless times I wished I had some surgical putty that I could sculpt. I tell patients your face is not like clay, I can't sculpt it. But this offers that potential."

He said there is clear demand. Already cosmetic procedures are a $10 billion industry in the United States. And even during tough economic times, the number of procedures inched up 1.2 percent from 2009 and 3 percent the year before, according to the American Society of Plastic Surgeons.

In all, there were 13.1 million cosmetic procedures in the United States in 2010. The most common included breast augmentation, nose shaping, eyelid surgery, liposuction and tummy tucks, the society reported. The fastest-growing treatment were Botox and Dysport, which use a toxin to relax muscles and smooth wrinkles, and soft tissue fillers, such as Juvederm and Restylane, which augment features, including lips and cheeks. They were up 12 and 3 percent, respectively, last year.

The society also reported that there we 5.3 million reconstructive procedures performed last year, with tumor removals, laceration repairs and breast reconstruction on the rise.

Elisseeff, who is the director of the Translational Tissue Engineering Center in Hopkins' School of Medicine, said her goals are to benefit victims of trauma and disease, as well as those fighting the effects of aging.

Rosenblatt has been using Dysport between her eyes and Restylane for her eye sockets and cheeks. Now 37, she was recently back for a touch-up.

Over about 10 minutes, Dr. Byrne stuck her with multiple small needles, some through her mouth and into her cheeks. Immediately her features began to subtly fill and round, though Botox takes a few days for the full effects. Byrne said he aims for enough change that onlookers know there is something different, "more beautiful," but not enough to readily know what's not natural.

Rosenblatt said it's obvious to her when she looks at old pictures.

"I think I look refreshed," she said. "I think I look better now than I did five years ago. I can't give it up. It would be nice if it was a little more permanent."

Elisseeff's new material holds that promise because of its makeup. It's made of hyaluronic acid found in existing fillers, a naturally occurring component that gives young people's skin its elasticity, and a synthetic polyethylene glycol gel that is used to make surgical glue and contact lenses.

Alone, hyaluronic acid dissipates quickly, leaving users in need of regular treatments. The acid also can't be used over large areas in need of remodeling. And synthetic materials alone aren't so natural-looking and don't always age the same way as people.

Further, extensive reconstruction today often requires multiple surgeries that leave their own scars, Elisseeff and fellow researchers noted in an article they published about the material in the July issue of Science Translational Medicine.

Mixing biological and synthetic material isn't a new idea, but there are currently no similar products used for facial reconstruction or enhancement, according to doctors in the field. Elisseeff mixed different concentrations of each and injected them into the backs of rats until she found the one with the greatest long-term stability — more than a year with no deterioration during tests.

To get the material to maintain its shape, she used LED lights held close to the skin. The energy from the bulbs forms a study chemical bond between many individual molecules, similar to the way dentists filling cavities use lights to bond composite resin to teeth.

Once she found a formulation that worked, Elisseeff enlisted a small number of patients who were already undergoing tummy tucks to try out the new material. They had five drops of the material or hyaluronic acid alone implanted for 12 weeks before their procedure. The hyaluronic acid dissipated as expected, but the new material kept its size and shape.

She's already tweaked the material to address some inflammation that developed in the patients. And she's now working with an independent ethics committee to set up parameters for wider human trials and reaching out to doctors at Hopkins and in private practice to recruit patients.

Almost $2 million in funding going forward will come from the Department of Defense, which is interested in the applications for soldiers with blast injuries and others.

The original funding and inspiration came from a small Los Angeles cosmetic drug company, Kythera Biopharmaceuticals. Its co-founder and then-chief science officer said he'd been watching "Star Trek."

Nathaniel David said in this episode of the '60s sci-fi series Captain Kirk needed pointy ears and an upswept brow to disguise himself as a Romulan. That required only a quick trip to sick bay. David wondered how hard it would be to give real-life patients such easy access to desirable facial features, including noses, chins and cheeks.

He offered Elisseeff several million dollars to investigate the new frontier. And he now believes her discovery could be available in a couple of years, after extensive human trials expected to being as early as January.

"This technology would be more like painting than carpentry," he said. "You could have Brad Pitt's chin done in five minutes with no down time."

While no such technology is now available, there have been other advances in laboratories around the country. Much work is being done with patient cells, harvested from the nose or blood, to create custom bone, cartilage and skin for patients.

Elisseeff has also worked on other biomedical advances in tissues, adhesives and corneas.

Another company that has been working on biomedical advances is KCI, a medical technology company based in San Antonio, Texas. Dr. Ron Silverman, the chief medical officer, said research there already has led to changes in the way surgeons perform cosmetic and reconstructive procedures. Among KCI's products is AlloDerm, which is derived from human skin and is now commonly used in breast reconstruction after a mastectomy.

It comes in a sheet a couple of millimeters thick and is used to reconstruct the lower half of the breast, serving as a base and reinforcing the silicone implant that forms the top half of the breast while allowing for a more natural appearance. It also allows women to have their reconstruction in one surgery instead of two, shortening the ordeal and saving time and money, Silverman said.

The material is also used on burn victims.

Silverman, who is also a plastic and reconstructive surgeon at the University of Maryland and an adjunct associate professor at Hopkins, said other areas of regenerative medicine are promising for patients not well served by what's available now. He said he'll be watching progress made by Elisseeff, with whom he has collaborated in the past.

"We're watching what's going on," he said. "Something injectable like [Elisseeff's] material might provide an answer."

meredith.cohn@baltsun.com

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