Dermal fillers are substances that are injected into the middle layer of the skin, the dermis, to augment the skin and improve wrinkles, scars or to add contour to the face. Over the past twenty years, intense industry research has resulted in many dermal filler options and more fillers will be available in the US in the next few months.

The first physician to practice soft tissue augmentation was Neuber, who in 1893 took fat from the arms and transplanted it into facial defects.¹ In the 1940s and 1950s, the use of silicone was popularized, however, silicone was associated with disfiguring reactions called foreign body granulomas.  The use of silicone in the US was outlawed until a few years ago when a new form of silicone (intended for use in the eye) was approved by the FDA. The field of soft tissue augmentation had its turning point in the early 1970s when researchers at Stanford University began working with animal collagen as an implantable material.² Collagen injections for wrinkles became mainstream in the 1980s and its popularity soared after it became a popular topic in movies such as “First Wives’ Club.”  While Americans were enjoying the benefits of Zyderm and Zyplast collagen fillers, other countries began to experiment with different types of dermal fillers such as Restylane and Hylaform.  Zyderm and Zyplast required 2 skin tests at 6 weeks and 2 weeks prior to implantation and there was still a risk of allergy with these products even after 2 skin tests.  Restylane and Hylaform were made out of a naturally occurring sugar called hyaluronic acid (HA) that did not require skin testing. These products could provide immediate gratification because they could be injected on the first patient visit without fear of skin allergy. These HA fillers became popular worldwide and were available outside the US for many years prior to receiving FDA approval.  Currently there are seven HA fillers approved for use in the US and many more to come. Choosing which type of filler to use has become difficult for physicians and patients alike. This newsletter will attempt to explain the differences in the various dermal fillers.

Collagen is a naturally occurring protein in the skin.  Ultraviolet light, free radicals and other insults cause the body to produce collagenase, an enzyme that breaks down collagen.  Loss of skin collagen results in wrinkles.  Collagen can be injected into the skin to regain its youthful appearance.

Prior to introduction of human derived collagen and hyaluronic acid products, injectable bovine-collagen-containing products, Zyderm I, Zyderm II and Zyplast were used more frequently than any other materials for soft tissue augmentation and had become the standard to which all newer implants were compared. Zyderm I was introduced in 1977 as the first injectable bovine collagen and was approved by the U.S. Food and Drug Administration (FDA) in 1981. The FDA approved Zyderm II and Zyplast in 1983 and 1985, respectively.

The only difference between Zyderm I and II is the concentration of collagen (35 mg/cc with Zyderm I and 65 mg/cc with Zyderm II). This makes Zyderm II thicker and stiffer than Zyderm I. Zyplast contains 35mg/cc of collagen but this collagen is crosslinked with glutaraldehyde cross-linked which makes it last the longest of these three bovine collagen products. All of the bovine collagen products contain lidocaine, which reduces the pain of the injection.

Advantages

Effectively reduces wrinkles and scars.  Zyplast can be used to shape the border of the lips (vermilion border) and to treat deeper wrinkles.  Zyderm I can be used alone in superficial wrinkles or over Zyplast in deeper wrinkles. Because of the higher concentration of collagen in Zyderm II, this product is more suitable for moderate-to-deeper lines, wrinkles, and scars but it does not last as long as Zyplast because it is not crosslinked.  Zyplast is the most commonly used bovine collagen product and the results last approximately 4 months. The correction seen with bovine collagen products is temporary because enzymes called collagenase break down the bovine collagen, returning the skin to the way it was before the collagen was injected. The bovine collagen can be safely reinjected 3-4 times a year when necessary. Zyderm and Zyplast tend to cause less bruising than HA containing products and are currently the cheapest dermal fillers on the market.

Disadvantages

Bovine collagen products require two skin tests six and two weeks prior to treatment. A skin test is positive if redness, itching or firmness of the injection site develops. Such reactions can occur as early as six hours after the test, but most appear 48 hours or four weeks after the test.  If the skin test is positive, the patient is allergic to the bovine collagen and cannot be treated with these products.  Even with 2 skin tests the risk is never completely eliminated and can occur even after multiple collagen treatments have been preformed with no reaction. Although a patient may have one negative skin test result, there is still a 1.3 to 6.2 percent chance of hypersensitivity responses to treatment;³⁴ therefore a second skin test is necessary to lower the risk of adverse reaction to the less than 0.5 percent. If an allergic reaction develops, it usually resolves spontaneously within four to 24 months.⁵⁶⁷

Bruising, reactivation of herpes viruses, and bacterial infections may occur after treatment with bovine collagen implants. Necrosis (tissue death) resulting in erosions, ulcerations and scarring have been reported when Zyplast injections are used in the glabella (frown line area) therefore injection of this area with Zyplast should be avoided. In 0.04 percent of individuals treated with Zyderm or Zyplast prior to 1990, cysts were reported at the site of injection.⁸ Several steps should be pursued to avoid such complications: care should be taken to inject only into the dermis,⁹ antiviral medications should be used in people with a history of oral herpes infections, and use of Zyplast should be avoided in the glabellar region. While some physicians have speculated that autoimmune diseases, particularly polymyositis and dermatomyositis, might be triggered by exposure to injectable bovine collagen, studies have shown that the antibodies to bovine collagen do not cross-react with human collagen. Consequently, the likelihood of bovine collagen causing connective tissue disease in human hosts is remote.¹⁰¹¹

The drawbacks of bovine derived collagen, particularly the potential for adverse allergic reactions, led several companies to develop human-derived soft tissue augmentation material. Human-bioengineered collagen implants include Cosmo-Derm I, CosmoDerm II, and CosmoPlast. These products were approved by the FDA in March 2003. CosmoDerm I contains 35 mg/cc human-bioengineered collagen. The collagen concentration in CosmoDerm II is about twice as much as that found in Cosmoderm I. CosmoPlast has the same ingredients as CosmoDerm I, but is crosslinked by glutaraldehyde, making it last longer.

Advantages

No skin testing is required for these products as there is no risk of allergy; therefore, patients can be injected on their first visit to the physician. The cosmetic effects of CosmoDerm and CosmoPlast are immediate and last about 4 months.  These products tend to be associated with less bruising than the HA containing products.  In addition, CosmoPlast and CosmoDerm contain lidocaine which lessens the pain on injection. CosmoPlast has a slightly stiffer consistency than hyaluronic acid-containing fillers, which make it ideal for use in the vermillion border of the lip, the bridge of the nose, and to elevate the corners of the mouth.  It is often injected in medium to deep wrinkles followed by hyaluronic acid.

Disadvantages

Human bioengineered collagen is expensive to produce so these are the most costly fillers on the market.  The results last only about 4 months on average. Cheaper options are available but because these products have the least amount of bruising, redness, and pain, they are still frequently used in my practice.

Hyaluronic acid (HA) is a naturally occurring sugar in the skin. It has the capacity to bind water up to 1000 times its volume. This plumps up the skin, giving it volume and making the skin look more youthful. In its natural form, hyaluronic acid would break down rapidly. It is crosslinked to make it last longer when injected into the skin. Hyaluronic acid products at present do not contain lidocaine or other anesthetics; therefore some patients may require other methods of anesthesia.

Many products have been approved by the FDA for use in the United States and many more are coming.

Hylaform is an animal hyaluronic acid derived from rooster combs. There are 2 products in this family that are approved by the FDA: Hylaform and Hylaform Plus. These contain  5.5mg/mL of crosslinked HA.  Hylaform and Hylaform Plus are the softest of the HA products, due in part to the lower concentration of HA.  Hylaform is composed of medium sized particles while Hylaform Plus is composed of larger particles.

Advantages

No skin testing is necessary. This implant has a very natural feel in the skin. The softness of Hylaform and Hylaform Plus makes these ideal for use in the body of the lip and in large areas such as the cheekbones and jowls.

Disadvantages

All HA products are associated with bruising. Hylaform does not contain lidocaine, therefore injections may be painful. Use of topical anesthetics and dental nerve blocks can minimize the pain on injection.  The exact duration of effects of Hylaform and Hylaform Plus is not known but is thought to be about 3 months.

Captique is the same thing as Hylaform except that it is derived from bacteria rather than roosters. This bacterial origin makes Captique slightly stiffer than Hylaform.  It can be used in wrinkles, lips and scars.

Restylane is an HA product that is derived from bacteria.  It is the most popular and well known of the HA fillers.  At this time, only Restylane is approved by the FDA in the US but it is thought that Perlane will be approved here soon. Restylane is made of medium sized pieces of HA gel while Perlane is made of larger pieces of gel.  Restylane contains 20mg/ml of stabilized hyaluronic acid.  The increased amount of HA, and the bacterial origin of this product make it the stiffest of all the HA products on the market.  This stiffness makes it useful as a treatment for deep wrinkles and may contribute to the fact that Restylane is thought to last longer than Hylaform and Captique.  However, the stiffness is a drawback when Restylane is used by a poorly skilled physician. Bumps, lumpiness, and blue blebs can occur when this product is not injected properly.

Advantages

No skin test is required. Results are thought to last 6-9 months.

Disadvantages

All HA fillers are associated with bruising.  Redness and swelling are common complaints for the first 24 hours after injections. The stiffness of the product makes it better for deep wrinkles than for use in the body of the lip.  (I prefer softer products for the body of the lip)

Juvederm (also known as Hydrafill) is a bacterial derived HA that was approved by the FDA in late 2006. There are many kinds of Juvederm but only Juvederm 24HV (also known as Juvederm Ultra) and Juvederm 30HV (also known as Juvederm Ultra Plus) are currently sold in the US. Juvederm Ultra and Ultra Plus consist of 24mg/cc of hyaluronic acid.  Juvederm Ultra Plus has a higher proportion (11%) of crosslinked  hyaluronic acid than Juvederm Ultra making it more suitable for deeper facial folds and wrinkles.  In a study done at our center comparing Juvederm to crosslinked bovine collagen in the treatment of nasolabial folds, 81-90% of patients treated with Juvederm maintained a clinically significant correction of the treated sites in six months which was higher in a greater extent than the patients treated with bovine collagen.¹² Most patients favored treatment with Juvederm over bovine collagen.

Advantages

No skin test is necessary. The large amount of 24mg/cc of HA in the product and the 11% degree of crosslinking make this product last longer than products with less HA such as Hylaform.

Disadvantages

All HA products can cause redness, swelling and bruising.

There are many filler products on the market.  Those containing collagen and HA are the most commonly used.  These fillers can safely be used alone and in combination.  New fillers will soon be on the market.  It is expected that an HA filler containing lidocaine will launch in the US soon.  Perlane, a bacterial derived filler similar to Restylane that may last longer than Restylane, is expected to receive approval soon as well.

Please visit www.16skintypes.com if you have any questions. I will be happy to answer them!

Thanks for joining me,

Leslie Baumann MD