More Detailed Information on Dermal Fillers

Did you want to know more in depth details on the history of injectable fillers and how they work? Check this out! 

Hyaluronic Acid

Hyaluronic acid is the most prominent glycosaminoglycan in the skin. Hyaluronic acid potently binds to water and, when injected into the skin, volumizes, softens, and hydrates the skin. In addition to these benefits, it plays a role in cell growth, membrane receptor function, and adhesion.

Hyaluronic acid stabilizes intercellular structures and produces the viscoelastic network for collagen and elastin fibers to bind together. As seen with photoaging, these connections fail, thus resulting in disorganized clumps of collagen and elastin. These benefits make hyaluronic acid an excellent dermal filling agent.

Because hyaluronic acid is identical in all species, the risk of allergy is remote. Hyaluronic acid has a heparinlike effect, thus resulting in a greater incidence of bruising than is seen with collagen fillers. Until 2010, nearly every FDA-approved hyaluronic acid product in the United States did not contain lidocaine, thus significantly increasing the discomfort experienced with injection of these dermal fillers compared with the bovine- and human-derived collagen fillers. Despite these shortcomings, hyaluronic acid fillers still emerged as the leader of dermal filling agents for soft tissue augmentation, owing to their superior cosmetic results.

In the uncommon circumstance when an undesirable outcome occurs with hyaluronic acid, correction is possible with the injection of commercially available hyaluronidase, which breaks down the unwanted hyaluronic acid dermal filler. The use of hyaluronidase for this purpose is not FDA approved and is considered an off-label use. In many cases, 10-30 units of unpreserved hyaluronidase is sufficient to achieve the desired correction. Local site reactions may occur in up to 25% of persons, although they are typically transient and mild. Initial treatment with as little as 5-10 units is commonly recommended and is often effective, although some treat with as much as 75 units with few adverse effects. Additional corrections can be performed, although full correction may take up to 4 weeks to fully appreciate. Some preparations are bovine derived, and skin testing should be considered prior to treatment with these dermal fillers.

Hyaluronidase preparations are clear, concentrated liquids that are stored in a refrigerated vial. To reconstitute these dermal fillers, physicians typically add normal saline or lidocaine (with or without epinephrine). When using Amphadase, reconstitution using 3 mL of 1% lidocaine with 1:100,000 epinephrine has been commonly used with great success. After mixing, the vial is gently swirled. Prior to treatment, a skin test can be performed by injecting 3-5 units (0.06-0.1 mL) of the reconstituted solution into the superficial dermis at the antecubital fossa. A positive hypersensitivity reaction consists of a wheal appearing within 5 minutes and lasting 20-30 minutes, accompanied by local itching.

Juvederm (Juvederm Ultra/Juvederm Ultra Plus)

In 2006, the FDA approved Juvederm, which is also a nonanimal stabilized hyaluronic dermal filler. In the United States, only 2 types of Juvederm dermal fillers are FDA approved. Both Juvederm Ultra and Juvederm Ultra Plus contain 24 mg/mL of hyaluronic acid, but Juvederm Ultra Plus has a higher proportion of cross-linking than Juvederm Ultra. Juvederm is a homologous gel with the highest degree of cross-linking of any of the hyaluronic acid fillers and thus has a smooth consistency. In 2010, both Juvederm Ultra and Juvederm Ultra Plus became available with lidocaine, to reduce pain with injection, both labeled as Juvederm (R).

Table 5. Juvederm Dermal Fillers (Open Table in a new window)

Agent	Contents	Method of Action	Indications	Injection	Duration	Limits
Juvederm Ultra	Sterile, biodegradable, nonpyrogenic, viscoelastic, clear, colorless homogenized gel implant; cross-linked hyaluronic acid formulated to a concentration of 24 mg/mL suspended in a physiological buffer; hyaluronic acid is produced byStreptococcus equi bacteria	Adds natural volume as it integrates into dermal tissue; then, attracts and binds water molecules to help maintain volume	Depressed scars Facial contour enhancement, including lips Dermal atrophy from disease or corticosteroid injections Wrinkles, creases, and lines caused by facial expression or aging	One box contains 2 prefilled syringes, each containing 0.8 mL of hyaluronic acid; inject into mid dermis	Approximately 6-12 months	20 mL/60 kg (130 lb) body mass per year
Juvederm Ultra Plus	24 mg/mL of hyaluronic acid (same as above) but with a higher proportion (11%) of cross-linked hyaluronic acid	Same as above	Same as above	Same as above. Injected into mid-to-deep dermis	Approximately 9-12 months	20 mL/60 kg (130 lb) body mass per year

Calcium Hydroxylapatite

This novel filler, Radiesse, was FDA approved in December 2006 for the correction of facial wrinkles and folds and for the correction of HIV-associated facial atrophy. In 2009, it received FDA approval for cosmetic use in non-HIV patients as well. The dermal filler is composed of 30% calcium hydroxylapatite and 70% carrier gel. The clinical results may last as long as 12 months or longer, although the carrier gel lasts no longer than 6 months, thus often resulting in a slight decrease in correction at that time.

Radiesse is nearly always injected subdermally at the dermal-subcutaneous junction; thus, this product is not a true dermal filler. Studies from 2008 suggest that calcium hydroxylapatite may induce neocollagenesis, although further research is needed.

Because of the pain associated with injection, some practitioners add lidocaine to the syringe, without a clinical appreciable decrease in effect. Mariano Busso, MD, has treated numerous patients by adding 1 drop of 10% lidocaine to the previously available 1.3-mL syringe of Radiesse to decrease the discomfort associated with injection. Treatment of the hands has been accomplished with the addition of 0.15-0.23 mL of 2% lidocaine per 1.3-mL syringe of Radiesse. This can be accomplished using a nose-to-nose (female-to-female) Leur-lok connector to connect the syringe of Radiesse to a 3-mL syringe containing the lidocaine. At least 10 passes of the product back and forth between the 2 syringes is recommended to achieve adequate and even distribution of the lidocaine. This makes the consistency of the Radiesse slightly thinner, thus making it easier to spread when using a bolus injection technique. Similarly, this mixture is often preferred for the treatment of the temples.

In 2010, Radiesse was released, which contains lidocaine to reduce pain upon injection.