As the majority of the baby-boom generation, born between 1946 and 1964, pass the age of 50, the need for medical products combating age-related degenerative skin damage continues to expand. Recently there has been a lot of interest in hyaluronic acid (HA), a soft-tissue filler.

History of use

The first medical use of HA as a biomaterial was in 1961, when it was employed to substitute for a vitreous body in retinal-reattachment surgery. In 1977, it was used as a viscoelastic in cataract surgery. In 1985, the first crosslinked HA implant, stabilizing this biomaterial against degradation, was described. Crosslinked HA is also used for the prevention of adhesion in abdominal surgery and in the treatment of degenerative joint dysfunction.

The use of crosslinked HA as a filler material in the treatment of aging skin was first reported in 1992 and led to development of the first injectable HA dermal implant, Hylaform (Genzyme Biosurgery, Cambridge, MA). Since then, an increasing number of HA preparations for treating facial lines, wrinkles, and hypoplastic lips have been officially approved in the European Community and have emerged in the European market. Soon expected in Europe is a fourth-generation non–animal-derived double-crosslinked HA dermal filler, HyaLite, (A-Life Ltd., Edinburgh, UK). As testimony to the success of these preparations, European sales of HA-based dermal implants now far exceed those of collagen products.

Technique

Injection of HA is the same as for collagen products. Patients may experience a bit more pain because of the lack of local-anesthetic supplementation. HA is administered intradermally with a 30-gauge needle in amounts of about 0.5 to 1 mL. In contrast to collagen products, it is a clear, colorless, viscous gel that does not require refrigeration and may easily be stored in the office.

In clinical studies using crosslinked HA, no evidence of immunogenicity or hypersensitivity was found, and no systemic adverse events were reported. Therefore pretesting is not required; this is a distinct advantage of HA over bovine collagen, which carries the risk of severe allergic reaction. Reported adverse side effects, such as tiny intradermal knots, swelling, erythema, itching, and pigmentation/depigmentation, were local and transient.

With regard to performance, crosslinked HA is at least comparable to collagen, remaining in loco for periods ranging from several months to 1 year. Because no available studies have compared different HA preparations, it is not possible to determine whether differences exist with regard to duration of effect among noncrosslinked, single-crosslinked, and double-crosslinked HA. (“Single-crosslinked” indicates HA stabilization with 1 type of chemical bridge; “double-crosslinked” indicates the incorporation of 2 different types of bonds for even greater protection against biodegradation). But judging from clinical observations, it seems clear that efficacy of the treatment depends on patient characteristics, such as skin type and defect location, as well as mode of administration. This is also true of collagen.

As with collagen suspensions, HA, be it crosslinked or not, acts as a filler biomaterial and is degraded biologically with time. This may be an action of tissue macrophages (Figure 1). The question then arises: What remains after complete degradation?