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Injection of 'skin filler' material appears to stimulate collagen production

February 20, 2007

Injections with "dermal fillers" containing hyaluronic acid appear to stimulate production of collagen, a primary protein in the skin, and may partially restore the structure of sun-damaged skin, according to an article in the February issue of Archives of Dermatology, one of the JAMA/Archives journals.

Injectable skin fillers have become increasingly popular for correcting the lines and wrinkles associated with aging, as well as acne scars and other skin conditions, according to background information in the article. Hyaluronic acid, a compound that occurs naturally in the skin and connective tissue, is among the most widely used fillers in the United States. Its molecules bind to water in the skin, hydrating and firming its structure, and the loss of hyaluronic acid with aging is associated with skin dehydration and wrinkling. Because hyaluronic acid degrades rapidly in the skin, the commercially available version is cross-linked, or bound to itself chemically to increase stabilization.

Frank Wang, M.D., and colleagues at the University of Michigan Medical School, Ann Arbor, injected non-animal stabilized hyaluronic acid (NASHA), one of the most commonly used forms, into the forearms of 11 healthy volunteers (average age of 74 years). All participants were fair-skinned, and eight had moderate sun damage—visible as brown spots, drooping skin, wrinkles or uneven pigmentation—while three had mild to moderate damage. They received three injections of .7 milliliters of stabilized hyaluronic acid 2 to 5 centimeters apart in one forearm, and three injections of saline solution at the same volume and spacing in the other arm. Skin biopsy samples approximately 4 millimeters in diameter were taken from the site of the injection four and 13 weeks later.

It is commonly assumed that fillers achieve their effects by filling space in the skin; through examining the skin samples under an electron microscope, the researchers found that this appeared to be the case with stabilized hyaluronic acid. "To further investigate potential mechanisms for this filler's long-lasting cosmetic benefits, we assessed the biological response of skin to NASHA," the authors write. "We found that NASHA injections induce type 1 collagen production in photo-damaged forearm skin." Because there is currently no evidence that skin on different parts of the body behave differently, it is likely that hyaluronic acid has the same effect on facial skin.

"Overall, our findings indicate that NASHA injections induce robust collagen production through several potential mechanisms, including the mechanical stretching of fibroblasts [cells that secrete collagen proteins], stimulation of growth factors and inhibition of collagen breakdown," the authors write. "Of these, mechanical stretching may be the most important." This physical stretching of the cells encourages them to produce compounds that both support collagen growth and suppress chemicals that break down cells' structures.

These findings suggest that, in addition to its cosmetic benefits, hyaluronic acid may be beneficial in skin-wasting diseases that involve collagen deficiencies, such as those associated with HIV or steroid use.

JAMA and Archives Journals