5/30/2025
PITTSBURGH — In patients with diabetic foot ulcers that looked healed and met the current definition of a closed wound, closed ulcers with functionally defective skin that lost more body water were likely to re-open, according to a new National Institutes of Health (NIH) Diabetic Foot Consortium study, led by researchers at the University of Pittsburgh and published today in Diabetes Care.
The U.S. Food and Drug Administration (FDA) currently defines a closed wound as one where the surface is completely covered by new skin and has not had any discharge or drainage for two consecutive weeks.
But when it comes to wound healing, looks can be deceiving.
“A wound that
meets the FDA’s criteria of wound closure appears to be healed, but it may not be functionally closed,” said co-lead author Chandan Sen, Ph.D., professor in the Department of Surgery at Pitt, director of the McGowan Institute for Regenerative Medicine and chief scientific officer of Wound Healing Services at UPMC. “The skin may not be doing its job of providing a barrier to the outside world: The covering is there, but the covering doesn’t work, so it’s vulnerable to bacteria, dirt and allergens entering the body. We call these invisible wounds.”
However, invisible wounds have a telltale sign: more moisture evaporates through this compromised barrier compared with healthy skin. This can be detected with a simple handheld point-of-care device that measures trans-epidermal water loss (TEWL).
“Diabetic foot ulcers are a major complication among patients with type 1 and type 2 diabetes. These wounds heal slowly and have high rates of recurrence, which often leads to amputation and death,” said Sen. “Our research shows that high TEWL of closed wounds, marking defective barrier function of the skin, is followed by wound recurrence.”
The new findings suggest that restoration of skin barrier functionality should be incorporated into the existing definition of wound closure to ensure durable wound closure and to better identify patients at risk of wound recurrence.
Across seven U.S. study sites of the NIH Diabetic Foot Consortium, the researchers — led by Sen, Gayle Gordillo, M.D., and Sashwati Roy, Ph.D., M.S. — recruited 418 adult participants with type 1 or 2 diabetes and who had a recently healed diabetic foot ulcer. Using a handheld device, they collected baseline TEWL measurements from the closed wound sites and then followed these patients for up to 16 weeks to check for wound recurrence.
Of the 368 participants who completed the study, 79, or 22%, had wounds that reopened by week 16. Baseline TEWL values were higher for wounds that would go on to reopen than for those that remained closed.
Further analysis identified that patients with high TEWL values — greater than 30 — were about 2.7 times more likely to have the wound reopen compared to those with lower TEWL levels. Time to recurrence was also shorter in wounds with high TEWL.
“Our study suggests that a TEWL of 30 in a healed wound should be considered a red flag for recurrence,” said Gordillo, professor of plastic surgery at Pitt and senior medical director of UPMC Wound Healing Services. “Even though these wounds may look closed, the barrier is defective, so these invisible wounds deserve further care.”
According to Sen, measuring TEWL as part of standard practice for assessing wound closure could lead to better outcomes for patients with diabetic foot ulcers and other types of wounds.
“This study is an important initial step to give clinicians treating diabetic foot ulcers a reliable diagnostic aid for the first time to assess an individual’s risk of ulcer recurrence,” said Teresa Jones, M.D. program director for the Division of Diabetes, Endocrinology, & Metabolic Diseases at NIH’s National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK). “Foot ulcers are such a confounding issue with diabetes and being able to determine which wounds are at highest risk for recurrence could save many lives and limbs.”
Additional research is needed to assess the impact of interventions for treatment of healed wounds with high TEWL.
Other authors on the study were Shomita Steiner, Ph.D., of Pitt; Jordan Jahnke, M.S., Giselle Kolenic, M.A., Cathie Spino, Sc.D., and Crystal Holmes, D.P.M., all of the University of Michigan; Mithun Sinha, Ph.D., and Lava Timsina, M.P.H., Ph.D., of Indiana University; Michael Conte, M.D., of the University of California, San Francisco; Teresa Jones, M.D., of NIH’s NIDDK; Rodica Pop-Busui, M.D., Ph.D., of the University of Michigan and Oregon Health and Science University; and Geoffrey Gurtner, M.D., University of Arizona and Stanford University.
This research was funded by NIH/NIDDK grants (U01DK119099, U24DK122927, U01DK119100, U01DK119083, U01DK119094, U01DK119085 and U01DK119102).
PHOTO DETAILS: click images for high-res versions
Left photo
CAPTION: Chandan Sen, Ph.D., professor in the Department of Surgery at the University of Pittsburgh, director of the McGowan Institute for Regenerative Medicine and chief scientific officer of Wound Healing Services at UPMC.
CREDIT: Chandan Sen,
Right photo
CAPTION: Gayle Gordillo, M.D., professor of plastic surgery at the University of Pittsburgh and senior medical director of UPMC Wound Healing Services
CREDIT: Gayle Gordillo