Hyaluronic Acid Injections dermal filler – Belotero, Juvederm Voluma, Restylane. USA, UK, Canada, Australia

Hyaluronic Acid Dermal Fillers

After the bovine collagens, the emergence of different hyaluronic acid preparations has revolutionized the injectable filler market because they require no prior skin test. Hyaluronic acid, which belongs to the family of glycosaminoglycans, consists of repeated disaccharide units. e hydrophilic properties of hyaluronic acid attract water into the extracellular matrix and therefore increase the skin turgor. Hyaluronic acid is gradually degraded. In order to increase the durability of the various hyaluronic acid preparations, stabilization is usually obtained by cross linking with several substances, such as 1.4-butanediol diglycidyl ether, which is found in Restylane.

Hyaluronic acids can be derived from avian or bacterial sources; each product has its own, specific characteristics. Several preparations adapted for different injection depths are available for most products, which di er based on the concentration of hyaluronic acid and the degree of cross-linking, and thus the rate of degradation.

Hyaluronic Acid of Avian Origin

Cross-linked hyaluronic acid of avian origin became the first non collagen filler to be widely used. e Hylaform product family is based on hyaluronic acid derived from processed rooster combs. Several products with different viscosities allow the treatment of different dermal levels. e Hylaform product family, with an average content of hyaluronic acid of 5.5 mg/ml, is easy to inject due to its superior rheological proper- ties and is less palpable than some products of bacterial origin (Manna et al. 1999).

In 2003, data from a clinical trial comparing Hylaform with Zyplast for the treatment of nasolabial folds was presented to the FDA. A total of 480 patients were included in this study which, to our knowledge, has not yet been published. Based on the data that are available from the FDA, no difference between the products could be established. A er 12 weeks the mean (±standard deviation) wrinkle severity score, which ranged from 0 to 5, was 3.3±1.11 for Hylaform and 2.2±1.12 for Zyplast (http://www.fda.gov/).

Hyaluronic Acid of Bacterial Origin

Typical examples for bacterial hyaluronic acid products are the Restylane and Juvederm / HydraFill families. e hyaluronic acid used for these products has a lower molecular weight, but is used at a higher concentration than the avian products: 20 mg/ml for Restylane and 24 mg/ml for Juvederm / HydraFill.

e rheology of these products is less than that of avian hyaluronic acid, and therefore in- creased pressure has to be applied while inject- ing the material into the dermis. Furthermore, a er injection the product is much more palpable. For example, when treating nasolabial folds the product remains palpable as a threadlike structure for days or even months. e material dissolves more gradually, however, and so over- correction is not necessary.

In contrast to other hyaluronic-acid-based products, clinical trials focusing on safety and durability exist for Hyalform and Restylane. A randomized controlled clinical trial was conducted to compare the e cacy and safety of Restylane and Zyplast. A total of 137 patients were included in the intention-to-treat analysis. A er 6 months the authors concluded that Restylane was superior to Zyplast (based on the assessment of the Winkle Severity Rating Scale). e superi- ority of Restylane (i. e., where the investigator felt that Restylane was more effective) was observed in 56.9 % of their patients, compared to 9.5 % pa- tients in whom the investigator felt that Zyplast was superior (p<0.0001). ose patients in whom there was no difference between these products (33.6 %) were not included in the simple univariate statistics (Narins et al. 2003). Although the authors concluded that Restylane was superior to Zyplast, it was later determined by the FDA that these data were not su cient to claim the superiority of Restylane compared to Zyplast at the de ned study endpoint of 6 months. No such data exist at the moment for any of the other bac- terial hyaluronic acid products. However, clini- cal trials for Juvederm/HydraFill in the United States are underway and are expected to be com- pleted soon.

Combination of Hyaluronic Acid and Dextranes

Combination of hyaluronic acid, hydrox- proylmethylcelluose and dextranes, marketed as Matridex, is thought to be more durable than other products. However, there is as yet no good clinical data on its e cacy and safety.

Polylactic Acid

Polylactid acid (PLA) is a synthetic biodegrad- able material. It is basically the same substance as that used in suture material. When injected into the deep dermis it gradually stimulates collagen formation. is takes some time and the manu- facturer recommends three initial treatment ses- sions, each approximately 6–8 weeks apart. A er the three initial treatments the result are sup- posed to last for up to 2 years. erefore, PLA cannot be compared with a standard ller like hyaluronic acid where the e ects can be seen im- mediately and where the results gradually abate a er each injection.

is product has to be diluted with sterile wa- ter at least 2 h before injection. Although initially the recommended dilution for PLA was 3 ml, the current recommendation is to dilute it in a vol- ume of 5 ml. Some of our colleagues add 1 ml of a local anesthetic to decrease the pain associated with the injection. Only retrograde injection is recommended. Even when administered using the correct injection technique and the higher dilution, in some cases the needle will block dur- ing the injection, at which point the needle has to be changed.

us far, studies on the e cacy and safety of PLA are based mainly on the treatment of HIV patients with drug-induced lipoatrophy (Moyle et al. 2004; Perry 2004; Valantin et al. 2003). Only case reports and case series exist for the use of PLA for aesthetic indications (Rzany et al. 2004; Woerle et al. 2004). According to the manufacturer, a clinical trial covering aesthetic indications is under way in the United States.