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Wrinkle fillers-Hyaluronic acid gels (Restylane, Perlane, Captique)


A perfect wrinkle filler should meet a number of requirements. It has to be long-lasting, nontoxic, and fully biocompatible; it must never trigger persistent host responses (such as allergy, autoimmunity and chronic inflammation); it must be easy to remove or adjust noninvasively, easy to standardize and manufacture, and also be affordable and widely available. Well, you guessed it right: such filler does not exist. In fact, it is unlikely to come about any time soon.

This does not necessarily mean that you have to wait for decades to get your deep wrinkles or folds filled (assuming a filler is the best way to go in your particular case). In recent years, these has been significant progress in wrinkle fillers that changed the situation from dismal to promising. This article is about hyaluronic acid gel, a class of fillers which, by some measures, is an improvement over some older favorites like bovine collagen.

The choice of hyaluronic acid (HA) as a basis for creating a wrinkle filler makes good sense. HA is a nontoxic, biodegradable, biocompatible polymer naturally found in human skin. Compared to proteins, it has simpler structure, is more stable, easier to produce in bulk and nonimmunogenic.

A number of wrinkle fillers have been developed on the basis of HA. As of the time of this writing, the most widely used type of HA based fillers is the so-called stabilized non-animal hyaluronic acid gel (NASHA). The best known NASHA brands are Restylane, Perlane and Captique. A process by which NASHA is made is rather sophisticated. A specially bioingeneered bacteria produce HA nearly identical to the one found in human skin. Then HA is purified and treated with a cross-linking agent, which firms it up and converts it into a stable gel. Finally, the HA gell is dispersed in such a way as to create injectable microspheres. Depending on the degree of cross linking and the size of the microspheres, the products for different cosmetic purposes are produced. For example, Perlane is designed for treating deep folds and lip plumping, Resylane and Captique -- for moderate-to-severe wrinkles, and Restylane Fine Lines -- for ... well, you guessed it.

Do not confuse HA gel-based wrinkle fillers, which are injected under a wrinkle, with topical skin care products containing HA. Topical HA does not penetrate skin. It may act as a good moisturizing ingredient but has no effect on wrinkles.

Advantages of NASHA

NASHA has a number of advantageous features. Since it is very close structurally to natural human HA, very few people develop allergic or other immune reactions to it. No allergy test is required prior to treatment. This is an advantage compared to bovine collagen, which has a high rate of reactions and requires allergy testing. On the other hand, the more expensive collagen derived from human tissues culture has about the same low risk of causing allergic reaction as NASHA.

The effects of NASHA injections lasts for about 6-12 month, after which the treatment has to be repeated. It is better than 3-6 month for collagen injections, but still creates a recurring drain on one's wallet. On the bright side, if the injections have created any unacceptable irregularities, they should dissipate on their own in a few month.

Since NASHA is based on HA synthesized by bioengineered bacteria, there is virtually no risk of contamination by animal or human pathogens. This advantage might be eggagerated in some advertising materials because even animal or human derived products tend to have high degree of safety as long as the manufacturer has diligently used proper purification and decontamination protocols. Nonetheless, avoiding animal or human sources might provide an extra safety margin.

There is one other interesting advantage. As a natural polymer, HA can be broken down by a natural enzyme called hyaluronidase. If a patient develops any post inection bumps or irregularities, they can be quickly corrected by simply injecting hyaluronidase in the same area, which causes the filler to degrade quickly. The viability of this remedy has been tested and confirmed in several studies.

Disdvantages of NASHA


A short-lived inflammation and/or swelling at the injection site is relatively common. It usually resolves on its own in a few days.

Chronic allergic, inflammatory or other reactions to NASHA are rare but can occur. The persistent reactions reported in the literature included allergy, inflammation and sarcoidosis. However, the incidence is similar to other highly-biocompatible soft-tissue fillers. In some cases, injection of hyaluronidase helped accelerate the resolution of a reaction.

Occasionally, an NASHA injection may create a bump or an irregularity under the skin. This is often a result of improper filler selection, incorrect dose or insufficient experience of the administering practitioner. Make sure to find a board certified physician who has performed at least a few hudreds of such injections and also is familiar with the administration of hyaluronidase in case things go wrong.

As I mentioned, NASHA degrades and has to be reinjected every 6-12 month to maintain results.

Other hyaluronic acid (HA) based fillers

There are a number of animal HA based fillers on the market. (For example, Hylaform and Hylaform Plus contain HA extracted from rooster combs.) Their advantages and disadvantages are largely similar to NASHA. The main difference is that they come from animal sources and might present a somewhat higher risk of contamination with patogens potentially harmful to humans. The allergy risk may be higher as well. However, the magnitude of these additional risks, if any, is debatable because unbiased information is scarce, whereas the manufacturers tend to make risk comparisons in favor of their products.


Restylane, Perlane and Captique cost around $500-$600 per cc (cubic centimeter). A typical amount per treatment is from 3/4 to 2 cc. To maintain results, the treatment has to be repeated every 6-12 month. The fillers based on HA of animal origin tend to be about 20-30 percent cheaper than NASHA. Some experts maintain that they are less durable than NASHA. In reality, there isn't enough published data for a good durability comparison.

Bottom line

For certain types of deep wrinles and folds, an injectable filler may be the only viable alternative short of surgery. While no filler is ideal, HA gel-based fillers represent a reasonably good balance of durability, safety and reversibility for properly selected candidates.

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