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

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.

Biochemical and physical actions of hyaluronic acid delivered by intradermal jet injection route

“…Modification of the viscosity was shown to decrease friction of HA droplets in the skin and subsequently improve its integration without diminishing the bio‐stimulatory effect 15,21 . Low viscosity, especially in combination with high cohesivity, could be attractive in the treatments of the skin atrophy for which “good spreading ability” 12 of the HA filler is required (Table 2). Alternative in this case can be the administration of noncross‐linked HA (NCL‐HA).…”

“…For jet‐injected HA, longevity of its clinical effect relates to the dual nature of the action mechanism, as discussed above. Biochemical properties of hyaluronan guarantee the initial customer‐pleasing effect of skin hydration and volumization, but an unavoidable effect of hyaluronidase and ROS makes these benefits short‐living, irrespective of HA concentration or cross‐linking method 12 . The “true” clinical effect is determined by the generated tissue micro‐trauma and activated synthesis of ECM components.…”

“…Nevertheless, for the jet treatment, a subclinical level of inflammation could be desirable and would contribute to the soft tissue regeneration by activating an adjunct physiological pattern, without significantly aggravating postinjection morbidity and downtime. The inflammation comes from degradation of the injected HA polymer, either by intrinsic hyaluronidase or through oxidative de‐polymerization induced by reactive oxygen species (ROS) 12 . Percent of cross‐linking in commercial dermal fillers does not exceed 20% of HA chain, 11 so the unlinked portion is easily degraded and continuously “yields” small HA fragments.…”

“…The inflammation comes from degradation of the injected HA polymer, either by intrinsic hyaluronidase or through oxidative de-polymerization induced by reactive oxygen species (ROS). 12 Percent of cross-linking in commercial dermal fillers does not exceed 20% of HA chain, 11 so the unlinked portion is easily degraded and continuously "yields" small HA fragments. The lowweight pro-inflammatory fragments activate macrophages and induce chemokines maintaining a low inflammatory level in the skin all the time.…”

“…Biochemical properties of hyaluronan guarantee the initial customer-pleasing effect of skin hydration and volumization, but an unavoidable effect of hyaluronidase and ROS makes these benefits short-living, irrespective of HA concentration or cross-linking method. 12 The "true" clinical effect is determined by the generated tissue microtrauma and activated synthesis of ECM components. Although published data rarely report the treatment results beyond the 6-month efficacy, 26,28,30,32,33 Levenberg 27 demonstrated improvement in Fitzpatrick-Goldman wrinkle scale up to 18 months which was explained by continuous reorganization of the collagen during the final phase of the wound healing process.…”