BB&T

ATLANTA — Can the key to reducing hemorrhaging in a wounded patient be found in a single strand of hair? A group of researchers from Wake Forest Institute for Regenerative Medicine (Winston-Salem, North Carolina) is in the process of testing that theory and displayed their findings at the Society for Biomaterials (Mount Laurel, New Jersey) Translational Research Symposium here in mid-September.

What researchers have found is that a keratin biomaterial gel derived from human hair can effectively stop hemorrhaging in an acute liver hemorrhage model. Keratin is an extremely strong protein which is a major component in skin, hair, nails, hooves, horns, and teeth. The amino acids which combine to form keratin have several unique properties, and depending on the levels of the various amino acids, keratin can be inflexible and hard, like hooves, or soft, as is the case with skin.

To extract the gel, the hair is oxidized and sits out at night to gel. The result is keratin which has hemostatic properties.

"Rapid voluminous hemorrhage instigates a cascade of events that are difficult to reverse in the absence of advanced medical care," said Luke Burnett PhD, a member of the research team developing this process. "First responders often arrive at scenes of traumatic injury well beyond the point when the transfusion trigger has been reached and they are unable to implement life saving measures."

He added that "On the battlefield, ballistic injuries often result in death within the first hour. Currently tourniquets and hemostatic agents can be used by those in the field but these technologies have limitations that don't address the many unique demands of administering aid at the point of injury."

Usually a hemostatic dressing for first responders should be easy to transport and to store, while also being able to be used by non medical personnel on the injured. "The beauty is its biodegrable," Burnett told the audience. "It forms a thick coating that can be scraped off and it's pretty tough and resilient."

Burnett played a brief film to demonstrate how the gel worked. The blackish pellet-like substance was applied to a rabbits liver. Within minutes (according to Burnett) the blood had stopped clotting and "As you can see blood loss decreases dramatically and in as little as five minutes," Burnett said.

Keratin also has a great deal of regenerative properties.

Using a variety of in vitro assays the research team found that keratins increase Schwann cell proliferation, migration and attachment. In addition, keratins have the ability to self-assemble into fibrous and highly porous scaffolds suitable for cell infiltration and axonal growth. To determine whether a keratin hydrogel scaffold could facilitate functional nerve regeneration in vivo, a tibial nerve axotomy mouse model was employed.

The laboratory studies showed that keratin actually sped up nerve regeneration. The research team used a keratin-filled tube to attempt to repair a 4 mm nerve gap in mice. The results from these animals were compared with animals treated with an empty nerve guidance conduit and with animals treated with a nerve graft.

After a month, 100% of the animals in the keratin and nerve graft groups showed visible nerve regeneration across the gap, compared to only 50% who got the empty conduit. The speed of repair was best in the keratin group.

To date the application has only been used on rats, rabbits and pigs. It is nowhere close to being perfected to be used in humans.

"More studies are needed to obtain statistical data and to test the efficacy of Keratin in a model with a vascular size similar to humans," he said.

When and if the application makes it to market, it will go head to head with other established hemostatic therapies such as HemCon Medical Technologies' (Portland, Oregon) HemCon Bandages and ChitoFlex dressings that are used by military and medical first responders as well as healthcare professionals around the globe. In May Hemcon teamed up with SanguiBioTech's (Witten, Germany) ChitoSkin technology platform to help further innovations in hemostatic bandages and wound care dressings for the acute-care market.

Z-Medica (Wallingford, Connecticut) makes hemostatic products as well with a QuikClot NoseBleed application, a product used to stop nasal bleeding.

Start-ups less likely to get biomaterials

Can a company actually build a medical device that will go into a patient out of the biomaterials it wants to?

That was the question posed to attendees at the conference. The answer, according to Carl McMillin, PhD, a consultant for biomaterials who heads up his own firm, Synthetic Body Parts (Brecksville, Ohio) is "Not really" – unless the company is a med-tech powerhouse.

Now smaller med-tech companies are forced into a biomaterials crisis, McMillin said, with companies taking little chance with providing their materials for fear of liability issues.

"The beginning of the biomaterials crisis began with the DuPont (Wilmington, Delaware) and Vitek series of cases in 1993," he told the audience.

It all started when Vitek altered DuPont's Teflon to create a new material, Proplast, which Vitek used to make implants to treat temporomandibular joint syndrome. Patients complained they had suffered injuries from failures of Proplast – and immediately took both companies to court.

In all, DuPont doled out nearly $26 million litigating more than 650 lawsuits.

"Even though DuPont won all the cases, with only one case won on appeal, it still cost them a great deal of money," McMillin said. "So they decided to stop providing biomaterials for medical devices – and they were then followed by other companies.

Exactly how bad was it or is it?

Well, for just a single instance, McMillin was released from AcroMed, now DePuy (Raynham, Massachusetts), a Johnson & Johnson (New Brunswick, New Jersey) company, because he was unable to get proper biomaterials to place in the medical devices that he was helping to develop.

But the bright spot was that the company wanted to keep him on as a consultant.

"Some people have to work all their lives to become a consultant. I was thrust into it," he quipped.

An equalizer for the med-tech industry came from the Biomaterials Access Assurance Act of 1998 (BAAA), which was enacted with the aim of preventing suppliers, such as DuPont, from becoming entangled in this type of product liability litigation.

Reaction to the now decade-old act is a mixed bag and still has many "flaws" and "exceptions" McMillin said. "Most major suppliers still want to see significant tort/product liability reform before they return to the market."

But it's a catch-22. While most want to see the law tested, if such a case ever made it to the courtrooms, then the law would have failed to offer the protection it was designed to give.

"If your company is a [billion-dollar powerhouse] and signs a 'hold harmless' agreement, you can get the biomaterials you need," he said. But if you're a small start-up don't even bother asking. This is very bad for the biomaterials industry because it's usually the small companies that lead in innovation."

But it's not all doom and gloom – there is still some hope for small med-techs looking to get good quality biomaterials.

Royal DSM's (Heerlen, the Netherlands) April acquisition of the Polymer Technology Group (PTG; Berkeley, California), a biomaterials company, is one such bright spot. Earlier this year, PTG said it expects to exceed $40 million in net sales in 2008, with above-average operating profit margin. It also said it expects more than 20% annual sales growth in the next three to five years, based on existing business and a pipeline of new products.

A high-profile company like Royal DSM will give PTG an even higher profile, McMillin said. He also touted Solvay (Brussels, Belgium), which expanded its product offerings even further, reporting its decision this past February to enter a new sector of the healthcare market with the launch of a biomaterials line, brand-named Solviva.

The Solviva line — a group of "ultra" polymers — are those materials that have an extremely high performance profile in terms of thermal, mechanical, and chemical resistance.

McMillin said these companies' contributions are much-needed, adding that DuPont wasn't coming back into the business of providing biomaterials to the medical device industry anytime soon.

The comment drew a reaction from a member of the audience who identified himself as a part of the medical device division of DuPont. "We're very open to talking to companies," the DuPont representative said near the final minutes of McMillin's session. "The current policy is we're willing to sit down and talk with companies as long as we're part of the process."

Innovating in rapidly changing landscape

The Society for Biomaterials (Mount Laurel, New Jersey) conference, titled "Advancing Discoveries from the Laboratories to the Clinic," addressed the role of med-tech innovation in the future of healthcare.

Such was the case for the keynote address, delivered by both Scott Bruder, vice president and chief technology officer of BD (Becton Dickinson; Franklin Lakes, New Jersey), and Jennifer West, director of Nanospectra Biosciences (NBS; Houston), a company that was spun out of research conducted at Rice University (also Houston).

"It's probably not surprising that most of the money spent on healthcare is spent in the U.S.," Bruder said to an audience of several hundred.

Nearly $5 trillion are spent worldwide on healthcare, according to graphs and information Bruder presented. Of that amount, "only" 8%, or $382 billion, was spent on medical devices and diagnostics. And of the $382 billion, nearly one-third goes solely toward medical devices.

The remaining 92% is spent on healthcare services, pharmaceuticals, hospital charges and other miscellaneous items.

"This country spends $7,000 per person a year for healthcare costs," he said. "Third-world and developing countries spend less than $1,000 a year on people and they are [in] the areas that are going to be growing the fastest."

He added that this situation puts the U.S. in a position where all eyes will be on it for changes in health reform over the next few years.

Part of the shift will have to come from paying close attention to changes and policies that are being developed to shape the healthcare industry.

Specifically, Bruder was questioned about one potential shift that could have immediate impact and that is the possibility of Congress giving FDA more power after the Supreme Court's ruling in Riegel v. Medtronic (Minneapolis).

Sens. Edward Kennedy (D-Massachusetts.) and Patrick Leahy (D-Vermont) introduced a companion bill to H.R. 6381, which has 62 co-sponsors in the House. That bill was introduced to ensure that individuals are not prevented by the Food, Drug and Cosmetic Act (FDCA) from suing device makers under state tort laws. It could potentially give FDA more far-reaching powers.

"I think if you work with [FDA], they'll have the ability to help you go through the regulatory path, Bruder said. "But if you overstep your bounds, they're going to come down on you hard."

While FDA loomed large in the keynote address, some questioned how to better work with the agency and when was the right time to take a product into commercial development. It is a process that West said she is all too familiar with.

She was part of the research team at Rice University that led to the formation of Nanospectra Biosciences in 2000. The company's main goal is to help with the commercilazation of the AuroLase Therapy, which utilizes the unique "optical tunability" of a new class of materials developed at Rice.

These AuroShel particles (also known as nanoshells) can be designed to absorb different wavelengths of light, including the near-infrared wavelengths that can penetrate human tissue. The particles are delivered intravenously to the tumor and then the area is illuminated with a near-infrared laser. The particles will selectively absorb this near-infrared energy, converting the light into heat to thermally destroy the tumor and the blood vessels supplying it without significant damage to healthy tissue.

"I would argue that we started the company a little too early," West said. "We started it about two years earlier than we were supposed to."

She said that the company had to deal with the dry financing period of 2001, which forced it to look toward the government for funding. West added that there needed to be more research on the therapy before the company was founded.

But NBS has had a happy ending, with an IDE approved for AuroLase Therapy and a Phase I clinical trial beginning this year.