Filler science 101

Key Points

Irvine, Calif. - Choosing the best hyaluronic acid (HA) dermal filler for a particular patient demands that dermatologists understand concepts such as how filler formulation affects persistence and other performance parameters, an expert says.

Physicians frequently hear terms such as "cross-linked" and "NASHA" (non-animal, stabilized hyaluronic acid), he says. "And until recently, they just took their meanings for granted. They didn't really know what those terms meant."

To that end, the company has delivered presentations on the science of HA fillers globally to more than 1,500 injectors and is producing an ongoing series of publications on this topic, Dr. Tezel tells Dermatology Times.

Anatomy of a filler

One recently submitted publication focuses on manufacturers' need to balance persistence with concerns for ease of use, he says.

"If one just injects HA without modifying or cross-linking it, it will be absorbed by the skin within a week," Dr. Tezel explains. Overcoming this limitation requires the use of cross-linkers, which he defines as "very small chemicals that bind HA chains to each other so that all the HA chains act as a single unit."

In unmodified HA, polymer chains remain independent, giving this material a highly viscous liquid consistency, he says.

"Cross-linking the chains fixes them in position, creating a gel" that's useful for cosmetic injection, Dr. Tezel says.

Another important concept is the degree of cross-linking, or how much one modifies the product.

"The higher the degree of cross-linking," Dr. Tezel says, "the more cross-linkers in the product. And the more cross-linkers in a product, every other parameter being equal, it should achieve more persistence."

In scientific terms, a filler's degree of cross-linking indicates the percentage ratio of HA disaccharide monomer units to the cross-linker molecule (in this regard, U.S. manufacturers use either 1,4-butanediol diglycidal ether/BDDE or di-vinyl sulfone/DVS), Dr. Tezel explains. A 4 percent degree of cross-linking, for example, means on average that there are four cross-linker molecules for every 100 disaccharide monomeric units of HA, he says.

Although a high degree of cross-linking is desirable, too much cross-linking may reduce the hydrophilicity of the HA polymer chains, which could compromise a filler's volumizing effect, Dr. Tezel points out.

Extremely high degrees of cross-linking also might affect a filler's biocompatibility, he says. Therefore, he says it's wise for dermal filler manufacturers to maximize the degree of cross-linking while avoiding any undesired complications.

Differing products

Furthermore, Dr. Tezel says different manufacturers approach such challenges differently.

"Even though the ingredients of the HA recipe are pretty much the same," he explains, "the manufacturing processes of all HA dermal fillers are very different."

They differ in terms of how manufacturers cross-link the HA, how they size HA particles and whether they add a lubricant or uncross-linked HA to ease extrusion, Dr. Tezel says.