Patients with diabetic foot wounds increasingly receive healing products that stem from an unusual source: foreskin from circumcised babies.
The products, brand-named Dermagraft and Apligraf, are made of cells extracted from the foreskin and cultured to produce billions of similar cells. The healing products bear no resemblance to foreskin, which is simply the source of the cells, proteins and other agents that reside in the thin, plastic-looking strips placed on the wounds.
“I know when they told me about it, I kind of went, 'Oh, my goodness, I could have gone without knowing that,' ” said Wilma “Willie” Lehn, a 78-year-old Omahan who has had three applications of Dermagraft on a big-toe wound.
One friend kidded her, asking what might grow out of the foot.
Diabetic foot ulcers and venous leg ulcers are difficult to close because they receive inadequate blood supply. They can lead to foot amputations and death. Doctors in the Omaha area who use Dermagraft and Apligraf say the products can be more effective than simply cleaning the wound and placing gauze over it. Foreskin from circumcised infants is used because those cells are new and high-energy.
The products, which have been around for about two decades and are gaining popularity among wound doctors, represent a form of regenerative medicine. Regenerative medicine uses cell therapies and other substances in the effort to grow tissue and organs.
Medicare reimbursement for the expensive products is a concern for some who make and apply the products. The products currently cost a clinic roughly $1,700 per packet or container used for one session with a patient.
Beginning next month, Medicare reimbursement to hospital-related clinics using those products will be lumped in, or “bundled,” with other costs, such as clinic supplies and overhead. Further, in that process, the costs of Apligraf and Dermagraft will be averaged with less-expensive wound care products, the CEO of the maker of Apligraf said.
Clinics expect to receive less money for the product and probably will use it less as a result.
Apligraf and Dermagraft typically are used only on some of the most stubborn wounds.
Edward Kolar, an 84-year-old Omahan, recently was on an examining table in Dr. Shane Schutt's clinic at Methodist Physicians Clinic HealthWest, near 161st Street and West Dodge Road. The diabetic ulcers on Kolar's feet and one ankle had received a couple of applications of Dermagraft over the previous two weeks.
“It's gettin' better,” Kolar said to Schutt's physician assistant, John Olin. “Whatever you used works real well.” He lost his two big toes to diabetic foot ulcers a year ago.
Olin tweezed dead skin out of the wounds while Kolar lay back and looked up at the ceiling. The wounds bled. His feet have diabetic neuropathy, so the wounds cause him little or no pain.
That's one of the problems with diabetic foot ulcers — patients can have open wounds on their feet, especially on the bottom, and not know it. Then the wounds can become infected, causing catastrophic problems.
“I was just contemplating how I used to come out here to hunt rabbits,” Kolar said of the area, which now is west Omaha. “Probably about 1944, 1945.”
His wife of 61 years, Vianna, and their son, Tom, sat in the exam room with him. “He's doing good, I think,” his wife said.
Olin probed a bit more into the wound on his ankle, where Kolar still has feeling. “Ah. Ah. Ah. Uh,” said the old Marine, who also was a businessman and a banker at various points in his life. “I don't holler unless it hurts,” he said.
Olin measured the wounds and found that they had closed a little since last visit. “That's good news, Pa,” Tom Kolar said to his father.
Schutt, an orthopedic surgeon, entered as medical assistant Darrell Jones used water to thaw out a frozen packet of Dermagraft. Schutt cut small circular strips of the thin Dermagraft tissue and placed them into the raspberry-colored, dime-sized wounds. It took only a few minutes to apply the material to six wounds. Jones then dabbed at the oozing areas with gauze and covered them.
Clinical studies have indicated that the products work some of the time. When compared with conventional treatment of removing dead tissue, using saline-moistened dressings and keeping the patient off the foot, 30 percent of patients on Dermagraft gained wound closure in three months. That compared with 18 percent receiving routine treatment in the study done in 2003. An Apligraf study in 2001 found that 56 percent of patients gained complete healing compared with 38 percent treated with conventional care.
Dr. Brad Copple, a podiatrist with Miller Orthopedic Specialists in Omaha, said he learned about Dermagraft while doing his residency training at Yale University six years ago. He applies roughly 350 packets of the product a year.
“The bottom line is, it's a good product,” Copple said. “It works.”
Diabetic foot ulcers are “a time bomb” for patients, Copple said. The federal Centers for Disease Control and Prevention reported that 68,000 people in 2009 lost feet or the lower part of legs because of diabetes.
Copple said Dermagraft “jump-starts a wound to heal itself.” The product provides proteins, cells and collagen, which is a building block for human tissue, and stimulates the body's healing agents, summoning them to the wound.
Dr. Timothy Fitzgibbons, medical director of the Alegent Creighton Wound Care Center, said he uses Dermagraft and Apligraf a few times a week. Diabetic foot ulcers and venous leg ulcers can remain open for many months. “We want to do anything we can do to get these wounds to heal,” he said.
Dr. Steven Black at the Center for Wound Healing of the Nebraska Medical Center said Dermagraft and Apligraf are “no miracle” but are another tool to close wounds.
Geoff MacKay, CEO of Organogenesis Inc., the maker of Apligraf, said the product is expensive because it took $400 million over 15 years to create, test and gain federal approval for use in venous leg ulcers in 1998 and diabetic foot ulcers in 2001. The product was developed by an M.I.T. scientist in the 1980s.
Further, MacKay said, high costs come with ensuring quality, safety and long-term storage of cell lines.
An Organogenesis spokeswoman said only 13 foreskins have been needed to produce the cell lines over the past 15 years. The cells grow over and over, Angelyn Lowe said.
Organogenesis hit $100 million in revenue three years ago, MacKay said. Apligraf is its primary product. Dermagraft sales increased to $154 million in 2012 from $147 million in 2010, said a spokeswoman for the maker of the product, Shire Regenerative Medicine.
The change in Medicare reimbursement will hurt his company and patients, MacKay said. Medicare compensation for Apligraf and Dermagraft in hospital-related clinics will decline, he said.
The Center for Medicare & Medicaid Services said it recognized that there are higher-cost and lower-cost wound products and developed two distinct bundles for the procedures. The CMS maintains that reimbursement is based on hospital data and will be fair and accurate. Reimbursement will total $1,371 for most procedures using the products, and more for particularly large wounds.
Erin Mass, reimbursement manager at the Nebraska Medical Center, said comparing the 2013 CMS rate with that of 2014, the hospital's Center for Wound Healing would receive considerably less for using the two products if the volume of use remains the same. The difference totals about $58,000, Mass said.
Diabetes is a huge problem in the U.S. The CDC estimated two years ago that close to 26 million Americans have the disease.
Willie Lehn is one of them. She dropped something on her foot — she doesn't know what because she has no feeling in the foot — and crushed it. She underwent surgery, and a surgical wound has refused to close in three months. She has had three applications of Dermagraft, and she said the wound on her big toe has clearly begun to heal.
“I think it's a very interesting procedure,” she said of the novel use of foreskin. “I hope they find other things that they can use it for.”
Back in Schutt's west Omaha office, Edward Kolar's appointment was about over. He can still walk some but uses a wheelchair most of the time because of the sores on his feet.
“It's a real interesting product,” Schutt told the Kolar family. “Obviously, I'm a believer.”
He asked the Kolars if they had any questions.
“I think there's a great deal of hope here,” Vianna Kolar said.
“Any questions you have, Dad?” asked son Tom. “Besides the meaning of life?”