Hyaluronan Dermal Fillers: Efforts Towards a Wider Biophysical Characterization and the Correlation of the Biophysical Parameters to the Clinical Outcome

Abstract

Introduction: Hyaluronic Acid (HA) fillers are among the most used products in cosmetic medicine. Companies offer different formulations to allow full facial treatment and/or remodeling. Gels are being studied to establish the biophysical properties behind the specific clinical use and a correlation between the gel biophysical properties and their clinical performance. Clinicians' awareness is growing about the potential benefit deriving from such biophysical characterization.

Aim: The Aliaxin^® line of HA dermal fillers is the object of this study. The study aimed to widen the biophysical characterization of these gels by investigating a variety of properties to better support their optimal use. Further, we aimed to provide some clinical findings to gain a deeper insight into the correlation between filler features and clinical outcome.

Methods: The four gels of the line were investigated, for the first time, for their cohesivity and stability to Reactive Oxygen Species (ROS). Additional secondary rheological parameters; evidence of relative water-uptake ability; and some clinical findings on product safety, palpability and duration of the aesthetic effect are provided.

Results and conclusion: The gels proved highly cohesive and sensitive to ROS action with stability declining with the decrease in the overall gel elasticity. The G* and complex viscosity values at clinically relevant frequencies and gel water-uptake ability are consistent with the relative clinical indication related to gel projection and hydration capacity. Clinical outcomes showed the safety of the products and a perception of palpability well correlating with the cohesive/viscosity properties of the gels. A similar duration of the aesthetic effect (up to 1 year) was observed despite the diverse in vitro gel stability. The results broaden our knowledge of these gels and may contribute to optimize their clinical use towards the improvement of patient safety and satisfaction. Initial clinical observation indicated that gel biophysical properties allow for a reliable prediction of gel palpability, while in vitro data on gel stability cannot be related to the duration of the observed skin improvement. The latter finding further corroborates the idea of a skin restoration process activated by the gels besides the physical volumetric action.

Keywords: cohesivity; degradation; dermal filler; palpability.

Figure 1

Gel hydration capacity. A photo showing an amount of fillers (160 mg), before and after swelling in PBS. The increase in volume is noticeable. The gels were stained with toluidine blue to better visualize phase separation and were centrifuged before acquiring the image. It is evident that AFL and ASR did not reach their maximum swelling under these conditions. The image gives an idea of the relative hydro-action of the gels.

Figure 2

Rheological parameters of the HA-based fillers. Complex modulus (G*) (A) and tan delta values (B) determined within the linear viscoelastic range, at 1.59 Hz frequency. Shear stress vs strain curve (C). Values of complex viscosity measured at 0.159, 0.7 and 2 Hz frequency at a strain value within the linear viscoelastic range (D).

Figure 3

Gel degradation in the presence of ROS. (A) G′ values for the gels during incubation with ROS, compared to a control (filler incubated with water). (B) Quantitative evaluation of the degradation rate: extent of G′ decreases, normalized to the control (%), at increasing time of incubation with the ROS generating system. The data refer to a single measurement.

Figure 4

Results of the cohesivity test. (A) Representative images captured at diverse time points of the experimentation (15ʺ, 70ʺ and 90ʺ). (B) Cohesivity score attributed to the gels by four raters according to the Sundaram–Gavard scale.

Figure 5

Representative pictures of two patients obtained before and 12 months after the last of three treatments performed at 3-month intervals. Patients provided written informed consent for the use of the images for scientific research.