Marcos Borrell

Lift capabilities of hyaluronic acid fillers

Abstract Background: The lift capacity of a filler (ability to oppose deformation and flattening) relates to its suitability for correcting deeper wrinkles and folds, volumizing, and contouring. Lift capacity, considered as a function of both elastic modulus (G′) and gel cohesivity, can be expected to differ among products owing to proprietary manufacturing processes. Objectives: To compare the lift capabilities of 24-mg/ml smooth, cohesive gel fillers (with ∼6% and ∼8% crosslinking) and a 20-mg/ml granular consistency gel filler (∼2% crosslinking). Methods: G′ was measured using a parallel plate rheometer and the products were subjected to a small oscillatory strain. Cohesivity was measured using a linear compression test (quantitative) as well as a dye diffusion test (qualitative). Results: The 24-mg/ml smooth, cohesive gel filler had a lower G′ coupled with lower susceptibility to yield to a given strain versus the 20-mg/ml granular consistency gel filler. Both 24-mg/ml smooth, cohesive gel filler formulations demonstrated greater resistance to deformation in the linear compression test and lower rates of dye diffusion than the 20-mg/ml granular consistency gel filler. Conclusions: The 24-mg/ml smooth, cohesive HA gel fillers achieve a high lift capacity by combining higher cohesivity with lower relative G′ versus the 20-mg/ml granular consistency gel filler.

In Vitro Resistance to Degradation of Hyaluronic Acid Dermal Fillers by Ovine Testicular Hyaluronidase

BACKGROUND Although adverse events are uncommon with hyaluronic acid (HA) fillers, the use of hyaluronidase permits the reversal of treatment complications or overcorrection. OBJECTIVE This study sought to determine an in vitro dose‐response relationship between ovine testicular hyaluronidase (OTH) and three HA dermal fillers (24‐mg/mL smooth gel, 20‐mg/mL particulate gel, and 5.5‐mg/mL particulate gel with 0.3% lidocaine). METHODS AND MATERIALS The dose response of each was measured after incubation for 30 minutes in concentrations ranging between 5 and 40 U of OTH. Timed responses for the 24‐mg/mL and 20‐mg/mL HA fillers were obtained after incubation with 20 U of OTH for 15 to 120 minutes. RESULTS After all dose responses and timed‐interval tests, the 24‐mg/mL HA smooth gel filler exhibited more resistance against in vitro enzymatic degradation to OTH than the 20‐ and 5.5‐mg/mL HA particulate gels. CONCLUSION This resistance to degradation in vitro may be attributed to the higher HA content of the 24‐mg/mL HA smooth gel, the degree of crosslinking, and the cohesive property of the gel filler. This study was funded by a grant from Allergan, Inc., Santa Barbara, CA. Derek Jones, MD, is a consultant, investigator, advisory board member, and speaker for Allergan, Inc. He received no compensation for this study. Drs. Tezel and Borrell are employed by Allergan, Inc., Santa Barbara, CA. Editorial assistance was provided by Health Learning Systems, a part of CommonHealth, Parsippany, NJ.

Response of authors: ‘Lift capabilities of hyaluronic acid fillers’

In response to the comments made by Edsman and Helander Kenne (1), the paper ‘ Lift capabilities of hyaluronic acid fi llers ’ (2) was initially prepared and tailored for an audience not familiar or profi cient in the area of rheology. Throughout the paper we leveraged terms already used in the fi eld and familiar to physicians (such as linear viscosity and gel hardness) in a conscious effort to defi ne them and adapt them to more accurate scientifi c terms (such as elastics or storage modulus). Some of the explanations were an oversimplifi cation of complex material properties and interactions; however, all these were conscious decisions in an attempt to connect with the audience and explain complex material physics and properties, based on a strong scientifi c knowledge, both for fi llers and rheology. By defi nition, the elastic modulus G ′′ is a measure of the energy stored by elastic deformation that can be recovered (representative of the elastic behavior of a material, or solid-like contribution), while the viscous (or loss) modulus G ′ corresponds to viscous dissipation of the energy of deformation (liquid-like contribution). These quantities were determined with a parallel plate rheometer, imposing an oscillatory shear strain on one plate while measuring an oscillatory shear stress (torque) on a second plate, with the fl uid being tested fi lling the gap between the plates (G ′ can be extracted from the measured stress that is in-phase with the applied strain, while G ′′ is related to the out-of-phase stress component). Not surprisingly, the values of the elastic modulus G ′ were signifi cantly higher than the viscous modulus G ′′ at low stress (representative of the fi ller behavior ‘ at rest ’ ); thus, it was said that these materials (dermal fi ller gels) display a ‘ solid-like ’ response, and therefore the relevance of publishing values of G′ (elastic modulus) to characterize the ‘ gel strength ’ or ‘ hardness ’ of such materials. Figure 5 showed typical results for strain sweep measurements of HA dermal fi llers. The plateau at which the magnitude of the elastic modulus remains constant is known as the linear viscoelastic region and, as Edsman and Helander Kenne correctly stated, it is generally used to determine an adequate range of strain at which to perform other rheological tests, such as the frequency sweep test, to characterize the rheological properties of viscoelastic materials. Presenting these curves was in fact relevant, although not discussed in detail to avoid misinterpretations or confusion. At small amplitudes of the oscillatory strain the gel will slightly deform; however, if the stress is removed, the gel will recover its original form and the structure of the gel will remain unchanged (this is the characteristic response of a solid elastic material to an external force). On the other hand, as the strain amplitude is increased (i.e. a higher external force is applied), the gel structure will be ultimately broken; in this regime a nonlinear behavior is observed, represented by a rapid drop of the storage modulus G′ . At this ‘ yield ’ point the material goes beyond its elastic limit, and the material starts to ‘ plastically ’ deform and fl ow (unlike elastic deformation, plastic deformation is not recoverable, so the gel will retain its ‘ new ’ confi guration or structure). A larger plateau indicates a gel that maintains its confi guration over a larger range of strains; that is, the gel wants to maintain its initial shape and form over a larger degree of deformation, quite relevant of dermal fi ller. The authors of the article appreciate the concerns highlighted in the letter but would like to once again highlight the fact that the article was tailored for an audience that is not familiar with the fi eld of rheology. The authors were not inclined to demonstrate their expertise in the fi eld by a fairly complex analysis such as the one outlined above. We believe that would have defeated the purpose and objective of the Journal of Cosmetic and Laser Therapy, 2011; 13: 200–201