Scaffolds, antibiotics and wound pressure show promise in treating diabetic foot sores

Vacuum Assisted Closure and KeraPac dressing offer benefit.

Issue: January 2006

Existing technologies such as acellular tissue scaffolds offer safe and effective ways to treat diabetic foot ulcers. Now some new products, including negative pressure wound therapy, living-tissue scaffolds and topical treatments, may offer physicians even more ammunition in the fight against bone infection and amputation.

One new treatment method, Vacuum Assisted Closure (Kinetic Concepts), a form of negative pressure wound therapy (NPWT), is the “blockbuster” treatment for partial diabetic foot amputation wounds, said David Armstrong, DPM, PhD, professor of surgery, chair of research and assistant dean at the Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science in North Chicago, Il. NPWT may yield a higher percentage of healed wounds, faster healing rates and fewer re-amputations than standard care, Armstrong said.

Armstrong, considered a leading expert on diabetic foot ulcers, teamed up with Lawrence Lavery, DPM, of the Texas A&M University Health Science Center College of Medicine, on a 16-week randomized controlled clinical trial comparing NPWT to standard therapy for partial foot amputation wounds. They published their findings in the Lancet.

NPWT provides intermittent or continuous subatmospheric pressure through a pump connected to foam dressing, with an adhesive drape to maintain a closed environment.

“The [VAC] device sucks out a lot of fluid; in reducing edema and also in kind of agitating the local cells, it stimulates new vessel formation,” Armstrong told Endocrine Today. “It forms healthy granulation cells, which then can allow us to put on skin grafts and things.”

Secondary amputation wounds are complex and difficult to heal, Armstrong and Lavery wrote.

Armstrong and Lavery enrolled 162 patients in the 18-center trial. Patients were aged 18 and older, with partial foot amputation wounds up to the transmetatarsal level and evidence of adequate perfusion. Most participants were men.

David Armstrong, DPM, PhD [photo]
David Armstrong, DPM, PhD, a leading expert on diabetic foot ulcers. He and Lawrence Lavery recently published a study in which negative pressure wound therapy yielded a higher percentage of healed wounds, faster healing rates and fewer re-amputations than standard methods.

The researchers assigned 77 patients to NPWT and dressing changes every 48 hours and 85 patients to standard moist wound care. Physicians treated wounds until they achieved healing or completed a 112-day active treatment period.

Faster healing/fewer amputations

More patients healed in the NPWT group than in the control group (56% and 39%, respectively, P=0.040), the authors reported. The NPWT group also healed faster than the control group (P=0.005), they said. Granulation tissue, based on the time needed to attain 76% to 100% formation in the wound bed, formed faster in the NPWT group than in the control group (P=0.002).

Both groups had similarly frequent and severe adverse events, with wound infection the most common event. No infections correlated with NPWT treatment, they said.

The NPWT patients were only 25% as likely as control group patients to need a second amputation. Three percent of NPWT patients and 11% of control group patients had a second amputation.

The VAC trial differed from earlier NPWT studies. For example, the patients in the VAC trial had larger and more complex wounds than patients in earlier studies. Also, earlier studies focused mainly on superficial neuropathic foot wounds that were seven or eight times smaller than those in the newer study (20.7 cm and 2.4 cm to 2.9 cm, respectively). The VAC study was also much larger than an earlier randomized, controlled trial.

GraftJacket: ‘Biological duct tape’

Armstrong and other surgeons have combined VAC with tissue scaffolds and biological agents. One leading scaffold is the GraftJacket (Wright Medical), a piece of skin from which the cells have been removed. Armstrong likened the scaffold to a building’s superstructure, or skeleton. The matrix loses antogenicity, reducing potential rejection, he said.

“The body identifies this as part of its own and then…it essentially morphs into that tissue,” Armstrong said. “It’s like biological duct tape,” he said.

Armstrong noted that chemical agents also prove beneficial. Delivering antibiotics locally avoids problems associated with systemic delivery such as toxicity and resistance formation, Armstrong said.

GraftJacket sutured into a foot wound. The acellular scaffold, already a popular joint reconstruction aid, is becoming a key treatment for diabetic foot ulcers.

A GraftJacket sutured onto an Achilles tendon. The GraftJacket, a leading acellular scaffold, is among the new treatments for diabetic foot ulcers.

Courtesy of David Armstrong

KeraPac debrides and delivers

An even newer product is on the horizon: KeraPac, a dressing of non-woven fabric with porous polyethylene/silica microcarrier beads and human keratinocytes. It is placed directly on the wound and removed several days later. Riley S. Rees, MD, professor of surgery at the University of Michigan, developed KeraPac, a product of KeraCure, Inc.

“Because it’s in a dressing configuration, it actually debrides the wound and the beads allow pus to get trapped between them and then the keratinocytes are proven wound healers,” Rees told Endocrine Today. “The beads are in a bag, like a tea bag.”

KeraPac does not deliver antibiotics, Rees said.

Rees had used topical glutathione, a chemical found in every human cell. However, despite some promising animal studies in the late 1990s, glutathione “turned out to be a compound which was not conducive to the development of a product for diabetic foot,” Rees said. Getting glutathione, an intracellular molecule, into cells is very difficult, he said.

KeraPac, a dressing of non-woven fabric with porous microcarrier beads and human keratinocytes (skin cells). The dressing, which looks like a tea bag, debrides a wound and delivers living cells to heal it. KeraCure, the manufacturer, is embarking on a multi-center clinical trial.

Courtesy of KeraCure

“[KeraPac] is an advancement because the cells actually have the ability to read what the wound needs so they can stimulate the cell to make more antioxidants and make growth factors and they can signal the cell to do all kinds of things that we don’t understand,” Rees said. “The cells have advantages because they have so many more things that they can secrete into the wound.”

With about 10% of Americans having diabetes, and 10% of that group suffering foot ulcers with a high amputation rate, Reese felt compelled to seek an effective wound treatment.

“At first, I was really interested in the notion that I could find a cure for diabetic foot ulcers,” Rees said. “I realized that the glutathione product wasn’t going to work … so we came up with this concept of a teabag with cells on beads.”

KeraCure conducted animal trials and a small safety study at the University of Michigan, said Gretchen Johnson, KeraCure’s president and chief operating officer. The firm has received FDA approval to enter KeraPac in a human clinical trial — 300 patients at 16 sites — in January. The trial is expected to end late this year. The study sites do not include the University of Michigan and Rees is not an investigative team member, Johnson said. After the study is finished, KeraCure plans to file a pre-marketing application with the FDA, she said. – by Matt Hasson

Armstrong and Younger are consultants for Wright Medical, Inc. Rees is chief technology officer of KeraCure.

This article also appeared in Orthopedics Today, a SLACK Incorporated publication.

For more information:

Armstrong D, Lavery L. Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomized controlled trial. Lancet. 2005; 366:1704-1710. Also available on www.thelancet.com. Accessed December 2005.