Study sheds light on how CL-HA stimulates collagen repair in skin

In the U.S. and around the world, the popularity of minimally invasive cosmetic procedures continues to increase. Soft tissue injectables, also known as dermal fillers, are popular procedures that improve the appearance of aging and sun-damaged skin by restoring lost volume and filling lines. A recent clinical study sheds light on how cross-linked hyaluronic acid, CL-HA, a widely used dermal filler, works to improve skin appearance.

Speaking today at the 68th Annual Meeting of the American Academy of Dermatology (Academy), dermatologist Dana L. Sachs, MD, FAAD, associate professor in the department of dermatology at the University of Michigan in Ann Arbor, Mich., presented findings of a study demonstrating how CL-HA stimulates collagen repair in the skin. These findings may partially account for the known clinical benefits of this type of filler.

Skin aging refers to two common types of aging - natural or chronologic aging and photoaging. Natural aging is characterized by fine lines, skin laxity, and uniform color of sun-exposed and sun-protected skin. Photoaging refers to accelerated skin aging due to the effects of sun exposure. With photoaging, deep, coarse wrinkles, skin laxity, redness and variable discoloration of sun-exposed skin is common. In both types of skin aging, tissue examination reveals that collagen, the major structural protein of the skin, is fragmented and reduced. In addition, the cells that produce collagen (fibroblasts) exist in a "collapsed" state, meaning that they are not producing collagen optimally or as efficiently as they can.

"From a clinical standpoint, dermatologists know that soft tissue fillers work by restoring volume loss and smoothing wrinkles in aging and sun-damaged skin because we can see immediate improvements in patients' skin," said Dr. Sachs. "This biochemical study of cross-linked hyaluronic acid conducted by researchers in the department of dermatology at the University of Michigan Medical School set out to try to explain what takes place at the molecular level to account for the observed clinical improvements."

Hyaluronic acid is naturally present and is one of the major components of the dermis, the deep skin layer. However, when used as a skin filler, hyaluronic acid must be stabilized (by a technique known as cross-linking), or it will rapidly disappear into the skin. Once hyaluronic acid fillers are stabilized, they are commonly referred to as NASHA (non-animal stabilized hyaluronic acid).

An initial study demonstrated an increase in the production of type I collagen (a primary structural protein in the dermis, which diminishes with normal aging) in all six participants four weeks following a single hyaluronic acid injection into photoaged forearm skin.

A study published in the Archives of Dermatology1 included 11 participants aged 64 to 84 who received hyaluronic acid injections in one photoaged forearm and saline injections in the other photoaged forearm. At four and 13 weeks post injection, skin biopsies were taken from the site of injection in both arms and analyzed in the laboratory using an electron microscope to examine the activity of fibroblasts, the cells that produce collagen. The results indicated that positive changes in the skin occurred at the molecular level in the samples treated with hyaluronic acid.

"Samples of skin injected with NASHA demonstrated evidence of increased newly created type I collagen, especially in the areas surrounding the filler," explained Dr. Sachs. "In addition, fibroblasts were observed at four and 13 weeks following injection to be in a 'stretched' configuration that correlates with increased collagen production."

While studies examining the biochemical effects of other skin fillers on collagen production have not been conducted yet, Dr. Sachs believes that other skin fillers likely would demonstrate a similar mechanism of action as NASHA.

"These types of biochemistry studies would be exciting to perform with other skin fillers in the future, as I think we would glean an even greater understanding of how fillers work," said Dr. Sachs. "Eventually, studies examining the mechanism of action of skin fillers would help dermatologists to better understand how to repair aging and photoaged skin and hopefully lead to better and longer-lasting results for our patients."

"There are a variety of treatment options for aging skin, and your dermatologist can recommend the best ones for you," reminded Dr. Sachs.
For more information on improving the appearance of your skin, go to the "AgingSkinNet" section of, a Web site developed by dermatologists that provides patients with up-to-date information on the treatment and management of disorders of the skin, hair and nails.


American Academy of Dermatology


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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