05:29pm Friday 20 October 2017

Miller School Wound Researchers Find Greater Risk for Pressure Ulcers in the Elderly

But a Miller School study shows that the bed sores that annually affect 2.5 million people in the U.S. may not be entirely preventable, especially in aging patients whose skin has lost the innate ability to protect against the continuous pressure of body weight on skin.

Published August 14 in the international peer-reviewed journal PLOS ONE, the study by Marjana Tomic-Canic, Ph.D., and a multidisciplinary team of researchers who developed a unique model to observe early changes in human skin that lead to pressure ulcers, found that, even with inadequate blood supply, young skin has a baseline level of protective inflammasome proteins that increase when skin is subjected to pressure. In contrast, the researchers found, aged skin has lower levels of inflammasome, which though critical to the tissue-repair process, do not increase under pressure. Instead, the tissue begins breaking down rapidly under load.

“This is the first insight into the initial changes that lead to the formation of pressure ulcers in human skin, and it suggests that physiological impairment due to age facilitates their development,” said Tomic-Canic, professor of dermatology and cutaneous surgery and director of the Wound Healing and Regenerative Medicine Research Program. “That is not to say we can stand down on prevention efforts. Rather, our findings should send a strong message to keep up prevention efforts, be vigilant for the earliest signs of a pressure ulcer, act quickly to prevent further progression, and recognize aging as a risk factor. We also hope this research provides new insights for the development of new treatment strategies.”

The second most frequent cause of hospital readmissions, pressure ulcers usually occur when bony, poorly vascularized areas of skin, such as the buttocks, ankles, heels and hips, sustain prolonged pressure and/or continuously rub against a bed, wheelchair or other surface. Yet, due to limited knowledge about the molecular pathogenesis of pressure ulcers, no treatment is currently approved by the FDA as effective.

Zeroing in on the mechanisms of pressure ulcer development, the researchers, who included faculty members from The Miami Project to Cure Paralysis, specifically found that, when subjected to a pressure load equivalent to a person lying on his or her back, young skin rapidly increases the level of inflammasome proteins, and maintains that increased level for four hours. In contrast, when subjected to load, aged skin produces no change in inflammasome protein expression and, within two hours, undergoes a succession of other morphological changes that contribute to tissue breakdown.

“In aged skin, the subepidermal layer shows signs of breaking and collagen alignment changes in response to load,” Tomic-Canic explained. “In younger skin, collagen maintains its structure longer, supporting the biomechanical property of the tissue. It intertwines in a basket-weave pattern and holds the tissue together. But in response to pressure, collagen fibers in aged skin lose this structure and become parallel, rather than intertwined. So they are not as strong and the tissue breaks a lot easier.”

Contributing to the study from the Miller School’s Department of Dermatology and Cutaneous Surgery were first author Olivera Stojadinovic, M.D., research assistant professor of dermatology and cutaneous surgery; Julia Minkiewicz, Ph.D., former post-doctoral research associate; and Andrew Sawaya, graduate student in the Program in Biomedical Sciences; and from The Miami Project to Cure Paralysis, Juan Pablo de Rivero Vaccari, Ph.D., research assistant professor of neurological surgery; Scientific Director W. Dalton Dietrich, Ph.D., professor of neurosurgery, neurology, and cell biology and anatomy, and Senior Associate Dean for Discovery Science; and Robert W. Keane, Ph.D., professor of physiology and biophysics.

Researchers from the Tissue Engineering, Regeneration and Repair Program at the Hospital for Special Surgery in New York also contributed.

For their study, “Deep Tissue Injury in Development of Pressure Ulcers: A Decrease of Inflammasome Activation and Changes in Human Skin Morphology in Response to Aging and Mechanical Load,” the researchers developed what is believed to be the first mechanical pressure model to assess the effect of load and ischemia, which is caused by inadequate blood supply, on human skin tissue of different ages.

Developed at the Hospital for Special Surgery’s Tissue Engineering, Regeneration and Repair Program, their Mechanical Explant Test System was calibrated to apply mechanical pressure equivalent to what a patient’s skin tissue experiences when lying on a flat surface to skin tissue in the laboratory. Calculated by the hospital’s Motion Analysis Lab, this pressure was applied to skin obtained from six female surgery patients. Three of the women, ages 29 through 35, were considered to have young skin; the other three, ages 54 to 60, were considered to have aged skin. Since their skin tissue did not have a vascular supply, they all mimicked ischemic conditions.

Applying pressure to the young, aged and a control group of skin at half-hour, one-hour, two-hour and four-hour intervals, the researchers found a difference in the orientation of collagen fibers in sections of the aged skin after two hours of static pressure. In contrast, no significant changes in collagen were found in young skin under load. They did find, however, that after four hours of static pressure, the young skin continued to express higher levels of inflammasome, which, acting as a double-edged sword, may lead to an excessive inflammatory response in ischemic young skin.

“Taken together, these data demonstrate that load/pressure triggers specific tissue response in skin, morphological changes and rapid inflammatory response that may not be entirely preventable,’’ the researchers wrote. “Furthermore, we provide evidence that aging markedly influences response to load, underscoring its role in development of PUs among elderly.”

University of Miami


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