The Science of Hyaluron Injectable Fillers
The use of injectable materials for filling or plumping up facial lines and wrinkles dates back to 1981 in the U.S. when collagen injections became available. From 1981 to 2003, for over twenty years, injectable collagen was the only available facial filler. While the injection process was easy, the popularity of collagen injections was limited as its effects were very short-lived usually lasting around 6 weeks or so. Because the collagen material was bovine-derived (from cows), a skin test was required prior to injection and a small percent of patients had allergic reactions, thus not being capable of treatment. Since 2003, a new synthetic material has become commercially available and collagen is now ‘a material of historic interest’ primarily. This new material is hyaluron or hyaluronic acid.
Hyaluron (HA) is produced today by fermentation in cultures of equine streptococci. The fermented material is then stabilized via epoxidic cross-links of the glycosaminoglycan chains. As a result of this processing method, the HA material does not cause immunologic sensitization and virtually no risk of allergic reactions. Hyaluronan is a polysaccharide that is an essential component of the extracellular matrices in which all human tissues differentiate. In certain tissues, such as the vitreous cavity of the eye and synovial joint fluid, it is the major constituent. Unlike collagen, it is identical across all animal species and microbes. The largest amount of hyaluronan resides in skin, where it is present in both dermis and epidermis. Hyaluronan’s high capacity for holding water and high viscoelasticity give it some unique properties that are useful in various medical and pharmaceutical applications. Because it retains moisture, hyaluronan is used in some cosmetics to keep skin young and fresh-looking. As we age, the water-holding capacity of our skin decreases as hyaluronan depolymerizes. Therefore, the retention or insertion of hyaluronan into the skin is theoretically helpful in wrinkle reduction.
HA can be rather rapidly degraded and is ultimately metabolized in the liver. Modern processing methods have produced more stable forms of HA that have much longer in vivo retention times. As degradation occurs over time, water is attracted to the material at the site of implantation. As the HA concentration decreases, more water bonds to it thus helping with cosmetic persistence. This feature is what probably accounts for its longer volume retention effects than bovine collagen. (isovolemic degradation)
A variety of differing grades of transparent gels are available, based on the same type gel from highly concentrated (20mg/ml)stabilized HA, which varies in particle size and subsequent indication. Restylane has a particulate size of 100,000 gel particles/ml, flows through a 27 gauge needle, and is indicated for mid-dermal applications such as deeper wrinkle reduction, as well as lip augmentation, nasolabial folds, and glabellar creases. Restylane has even been successfully used in the treatment of tear trough deformities.14 Restylane Fine Lines has the highest concentration at 200,000 gel particles/ml, can be injected through a 30 gauge needle, and is indicated for thin superficial wrinkles. The lowest concentration gel is Perlane at 8,000 gel particles/ml which is injected through a 27 gauge needle and is intended for shaping facial contours, correcting deep folds, and for lip augmentation.15 Restylane was FDA-approved in December 2003, Perlane received its approval in 2007. There are numerous manufacturers of HA injectable fillers which, in addition to Restylane, includes Juvaderm.
The universal HA composition makes the need for pre-injection skin testing unnecessary as the risk for hypersensitivity reactions is minimal. It is easily injected and flows nicely through small-gauge needles. While not permanent, its persistence is reported to exceed bovine collagen with estimates of between 4 and 6 months post-injection
Rare side effects, that I have not yet seen, include injection site inflammation at an incidence of 0.02% and local hypersensitivity reactions (swelling, erythema, and induration) at an incidence of 0.02% lasting a mean of 15 days.
As of today in 2008, HA injectable soft tissue fillers are the gold standard by which all future injectable filler materials will be compared.
Dr Barry Eppley
Indianapolis, Indiana