Irvine, Calif. — To understand the injection characteristics of a hyaluronic acid (HA)-based dermal filler and how the material performs
clinically, one must understand how it was made, an expert says.
"Multiple factors affect injectability or extrusion force. The two most important ones are known as G — the elastic modulus,
which refers to how hard a product is — and viscosity," says Ahmet Tezel, Ph.D., director of research and development, Allergan
Medical, Irvine, Calif.
To help dermatologists understand the concept of gel hardness, Dr. Tezel explains that if one sandwiches an HA gel between
two plates, the higher the gel's G value, the more force it will take to push the top plate a small distance horizontally
while holding the bottom one stationary. More specifically, he says G denotes the ratio of shear stress (force per unit area
of the plate) to the shear strain imposed (the ratio of the horizontal displacement to the vertical distance between plates).
When manufacturers design HA fillers, he says, "One of the limitations they face is injectability, because HA dermal fillers
are very viscous materials."
Part of the solution to this problem involves incorporating some unmodified or uncross-linked HA, which flows much more easily
than HA with molecules that are cross-linked, Dr. Tezel tells Dermatology Times.
However, he says, "The downside of using uncross-linked HA is that it doesn't provide persistence and is rapidly broken down
in the skin. So in the ideal filler, one wants minimal amounts of uncross-linked HA."
Cross-linking refers to the process by which U.S. manufacturers bind HA polymer chains to each other, currently by using either
1,4-butanediol diglycidal ether (BDDE) or di-vinyl sulfone (DVS), Dr. Tezel explains.
Both react with hydroxyl sites on HA chains, thereby slowing down enzymatic, mechanical and free radical degradation of dermal
fillers after they're injected into the skin, he adds.
"Besides adding uncross-linked HA," Dr. Tezel says, "another point of differentiation between manufacturers is how they size
down the gel mass" that results from linking HA polymer chains together. If they don't do this, he notes, "It will just clog
One approach to breaking down HA gel mass involves pushing it through sieves or screens.
The screens have openings of a certain size and shape that create particles of roughly corresponding size and shape, Dr. Tezel
says. "That specifically sized particle creates a gel with a granular consistency."
In contrast, he says Allergan does not use screens to specifically size its HA gel. Rather, Dr. Tezel says, "We create random
sizes and shapes" through a proprietary homogenization process.
"By creating random sizes and shapes," he explains, "we create a uniform consistency or a smooth-looking gel. The only HA
product in the United States that uses this type of formulation is Juvéderm."
If one looks at this product under a microscope, Dr. Tezel says, "One will not see it as a granular particle product. One
will see a very smooth formulation."
Manufacturing processes affect not only how an HA filler extrudes, but may also affect how the product feels to the patient
inside his or her skin, Dr. Tezel says.
Products manufactured by sieving techniques have a narrow distribution of gel particle sizes and usually a higher viscosity
unless they include additional uncross-linked HA, he says. However, Dr. Tezel adds, "The uncross-linked HA will be quickly
metabolized and won't contribute to long-term clinical outcome."