Turning Research into Products

Tissue Technologies trying to develop bandages for chronic wounds

Patients often came to his clinic with toilet paper or rags in their wounds, unable to afford prescribed bandages.

By:
Elizabeth Esfahani
Richmond Times Dispatch in NASVF.org

Their crudely swathed sores were not only painful, but lingered for months, and sometimes years, often making their treatments too expensive to maintain.

Ever since he was a child, Dr. Kelman Cohen, professor emeritus of plastic and reconstructive surgery at Virginia Commonwealth University, has been fascinated with the body’s ability to heal.

"When I was a young guy and said I wanted to study wound healing, people thought I was nuts. They said, ‘What’s there to study?’" he said.

But Cohen remained steadfast in his pursuit, researching tissue repair and directing the university’s Wound Healing Clinic for three decades.

For the past 12 years, he has focused on ascertaining why some wounds do not heal after undergoing normal treatment, an endeavor that has led to groundbreaking discoveries that could affect the care of these chronic wounds.

The findings also have spawned Tissue Technologies, a company in the Virginia Biotechnology Research Park that Cohen founded with partner Peter Stevens in 2000.

Like many recent startups, Tissue Technologies’ origins stem from ideas generated in an academic rather than business setting. It is one story in a relatively new area that higher-education institutions are exploring: the transformation of research into commercial products.

Chronic wounds affect more than 1.7 million people in the United States every year. The largest group afflicted is the bedridden, mostly elderly or paralyzed people, who develop pressure ulcers, more commonly known as bedsores.

Diabetics and those with vascular circulatory conditions are also frequently affected. About 240,000 diabetics develop chronic foot sores each year, while 500,000 have venous statis or leg ulcers.

The consequences of these wounds are often devastating, said Mary Crossland, a nurse and director of the Wound Healing Center at Retreat Hospital.

Diabetic ulcers often end in amputation, and the physical disfigurement and emotional pain that come with all types of sores take a great toll on the patients and their families, she said.

In the past, not much attention has been devoted to chronic wounds, as the federal government, the private sector and the medical community were slow to focus on this growing health-care problem.

But with the rising elderly population and the increasing incidence of diabetes, the care of these wounds is fast becoming a multibillion-dollar business.

Treatments that exist today, however, are often expensive and many times not reimbursed through Medicaid or Medicare, Crossland noted.

Average hospital cost for a pressure ulcer is $21,675 per case, while the average cost of healing a diabetic ulcer is $36,000, according to medical statistics.

And the cost of care involves not only money but time as well.

Medical professionals must go through the process of discovering the root of a wound’s development – such as poor nutrition or chain smoking – and then prescribe the long treatment needed to heal the lesion.

Another problem in care also stems from a long pervading mentality that a "wound is a wound," Cohen said. From a gunshot wound to a burn, they have all long been treated in the same fashion.

Cohen and his team of researchers decided to delve further into the mystery of the chronic wound and try to pinpoint the molecular cause for the body’s inability to heal.

By analyzing samples of human wound fluid in their lab, they discovered that a certain enzyme called elastase, which usually helps in the mending process, was at abnormally high levels in chronic wounds.

"When these materials are under control, it’s a good thing because they help what we call ‘debreed’ the wound – kill bacteria, get rid of the dead tissue," said Dorne Yager, an assistant professor of plastic and reconstructive surgery who works with Cohen. "But like anything else, too much of a good thing can be bad."

In chronic wounds, the enzyme did not seem to differentiate between bacteria and normal cells, so the sore became locked in an inflammatory state, killing the good and bad tissue, according to Yager, whose skills as a molecular biologist were key to the discovery.

The research provided insight into one way chronic wounds might be different from normally healing wounds, leading to the usual journal articles that follow such a discovery.

Cohen has found that the process of taking such a discovery and making it a commercial product is a whole different story – one for which his medical degree would be of little help.

He was, however, fortunate in his timing. It is likely that had his team’s discoveries come 25 or perhaps as few as 10 years ago, promising research is all it would have remained.

But the fate of academic research and the transformation of innovation into viable products fundamentally changed in 1980 with the passage of the Bayh-Dole Act.

This federal legislation, which has been referred to as the "’Magna Carta for university technology transfer," shifted the ownership and development of inventions to small businesses and nonprofits, including universities.

Before the transfer, the government retained ownership of federally funded breakthroughs, and institutions creating the technology were required to go through a lengthy and rarely successful appeal process to obtain rights.

Additionally, the private sector had little incentive to advance any government-owned inventions because they were licensed non-exclusively.

As a result, patents sat and accumulated – in 1980, the government held title to 28,000 inventions, only 5 percent of which were licensed to industry for development, according to the Council on Government Relations, an association of research-intensive universities.

The Bayh-Dole Act effectively discarded the government’s tight control over innovation, giving universities and inventors the opportunity to retain title and the incentive to transform laboratory findings into commercial products.

The results of such a change have been revolutionary, said Patricia Harsche Weeks, president of the Association of University Technology Managers and vice president of planning and business for the Fox Chase Cancer Center in Philadelphia.

Before 1980, U.S. universities received fewer than 250 patents each year and inventions were seldom divulged, according to the Association of University Technology Managers.

But from 1991 to 2001, reported disclosures rose 114 percent, from 6,337 to 13,569 inventions, and U.S. patents granted to universities and hospitals increased 136 percent, from 1,577 to 3,721 issues, according to the association. And since 1980, at least 3,870 companies have been created because of a license from an institution. The group estimates that technology transfer has contributed more than $40 billion to the U.S. economy and generated more than 270,000 jobs.

Now, more than 400 universities have embraced the role of technology caretaker. VCU is among them, creating its office of technology transfer in 1992. Before then, there was really nowhere for VCU researchers to go with their discoveries, Cohen said.

Currently, it is the job of Richard Franson, who has been the office’s director for seven years, to examine inventions from across the university and determine whether they justify being patent protected, trademarked or copyrighted.

If they do, he guides their creators through the invention process, helping them take the intellectual property, protect it and get it to the marketplace.

"When Dick came, it kind of turned things around," Cohen said. "We finally had someone who was saying, ‘If you have ideas, bring them here and we’ll try to develop them in a big way.’"

But it takes more than a good idea, Franson notes. Serendipity, money and business experience are essential ingredients in creating a commercially viable product.

"It’s a huge risk, a huge gamble to get to the end product," Franson said. "But the only way you are going to get that blockbuster [product] is through exploring."

Universities involved in the transformation of technology do so for the public’s betterment, but they also hope to create a product like the University of Florida’s sports drink Gatorade. Such a product will put the institution on the map and begin a flow of money and research talent.

While most innovations end up creating more modest products than the Gatorade, they usually require a university-private partnership to succeed.

This new relationship has been praised by many observers, although some warn that excessive commercialization of universities could occur if the trend is not carefully watched.

"I don’t think that the academic community has turned themselves over wholesale to commercial interests – but there is that danger, it is worth worrying about," Weeks said.

These public-private partnerships, while sometimes difficult, are needed because of the time and money needed to get products through federal regulations and brought to market.

For Cohen, the adventure began when he was contacted by Vince Edwards, a chemist in the Cotton Textile Chemistry Research Unit at the U.S. Department of Agriculture.

Edwards, who had read about the VCU researchers’ work in a journal, presented the idea of a re-engineered cotton bandage whose fibers would be designed to attract and pull the overabundant enzyme out of the wound.

It would be the first generation of "smart" dressings, complex bandages that would go beyond the capabilities of simple gauze.

By using cotton, the bandage would be inexpensive. That fact excited Cohen because the product would not be restricted to the industrialized world.

In collaboration with the USDA and VCU, Tissue Technologies licensed the technology in the United States and now seeks worldwide patent protection.

But even with the promise of an inexpensive product with an international market, Yager says, "We do have this constraint in finding money to pay for medical innovation and getting it to the people. It is more and more of a problem."

The company hopes to begin a small clinical trial in six to 12 months with one goal: to prove the bandage will take the enzyme out of the wound.

But as it moves to the next phase of development, it must find a way to finance the costs associated with market introduction.

A medical device like a bandage usually requires about $15 million, a cost that is equally distributed among the phases of product development, clinical studies and market introduction, said Peter Stevens, president of Tissue Technologies.

Since the bandage is not a drug and does not put anything into the wound, the price tag is relatively inexpensive compared to other biotech startups. A new drug might need half a billion dollars and 10 to 15 years to move from invention to marketplace, Franson said.

But even while Tissue Technologies’ first product is traveling on a more rapid path to commercial viability, the company, like most startups spawned at a university, still needs a partner with business experience and some serious investors.

"Academics, generally speaking, don’t have a firm grasp of what is happening in the real business world," Franson said.

Stevens, who agreed to tackle Tissue Technologies’ business side, can attest to the unique working relationship between academics and businesspeople.

"It is rather like men are from Mars and women are from Venus – neither of you can believe that the other can think that," said Stevens, a former business manager of a surgical specialty company.

While it took time, Stevens said the gaps between the two disparate mentalities have, for the most part, been bridged, and the road looks promising for Tissue Technologies, currently in confidential negotiations with two companies that will help bring its product to market.

But perseverance is still integral in this enterprise, Franson noted. Companies are not going to rush a product to market, which is why Tissue Technologies has been in negotiations for almost a year as interest in the gauze has worked its way up to the top ranks of the two companies.

"Inventors and partners, rightfully so, don’t want to jump on a bandwagon unless they are sure it’s not going to fail and put millions of dollars into it," Cohen said.

And their concerns are "things that in our little cloistered world we never even think about," Cohen said.

For example, one of the interested parties is based in Europe and was concerned with the product’s packaging, he said.

"Will Europeans buy a cotton product? Is it going to look too much like gauze that is not sexy enough?" are questions that have been raised, Cohen said.

And while it is an exciting time for Tissue Technologies, Cohen knows his company cannot subsist on one product alone. He is working with Edwards and the USDA on a slew of "smart" bandages that will expand upon their first product.

"At the end of the day, we should turn out a product that does more for the health, happiness and well-being of individuals than what I was able to do with a knife in the operating room for thirty years," Cohen said. "It hasn’t been easy, but it has been a great journey."

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