Elucidations on the Performance and Reversibility of Treatment with Hyaluronic Acid Based Dermal Fillers: In vivo and in vitro Approaches

Abstract

The aim of this study was to investigate the performance and the reversibility of different classes of Hyaluronic Acid (HA) dermal fillers. We analysed 4 HA based fillers, belonging to 3 different chemical classes of products, commonly used in the field of wrinkles correction: linear HA 8 mg/mL (Viscoderm 0.8), thermically stabilized hybrid complexes of high and low molecular weight HA molecules at a concentration of 32 mg/mL and 45 mg/mL respectively (Profhilo and Profhilo Structura) and cross-linked HA 25 mg/mL (Aliaxin GP). Methods: The products were tested by a well-established animal model. The generated implants were analyzed through High-Frequency Ultrasound technology. Then, reversibility of the treatment was evaluated by enzymatic degradation kinetics studies, characterised by a combined approach of Carbazole assay and HP-SEC/TDA method. Results: Implants generated by linear HA 8 mg/mL remained detectable by ultrasound acquisition for 4 weeks, whereas those generated by injection of HA hybrid complex 32 mg/mL were detectable for 10 weeks. HA hybrid complex 45 mg/mL and crosslinked HA 25 mg/mL were detectable for 29 and at least 33 weeks, respectively. Enzymatic degradation kinetics studies demonstrated that the HA content in HA hybrid complex 45 mg/mL was almost completely depolymerized and homogeneous after 3 h of treatment. For cross-linked HA 25 mg/mL, 24 h of incubation are needed to obtain the same degree of depolymerization. Conclusion:The study confirmed the ability of the experimental model to predict the behaviour of HA based dermal fillers in vivo and showed the innovative aspects of HA hybrid complex 45 mg/mL, that combines the high-safety profile, in terms of reversibility of the treatment, of the linear HA-based products with the durability of a high degree cross-linked gels, paving the way to the chance to be used for a wide range of applications in the field of aesthetic medicine.

Efficacy and tolerability of Profhilo® Structura intended to restore lateral cheek fat compartment: An observational pilot study

“…The efficacy of the studied medical device was also more pronounced 4 months after the start of the treatment compared with assessments at earlier time points in the study. These results confirmed the improved duration of stability of the medical device observed in in vitro and preclinical analysis, 28 suggesting an important role for this product in improving skin defects and the potential long-term effect of this formulation. Also, these data are especially important because the product is not a commonly used chemically cross-linked HA filler.…”

Between Beauty and the Law: Analyzing Cosmetic Filler Litigations in South Korea for Safer Medical Practices

“…Furthermore, the reversibility of HA fillers provides a safety net for both patients and practitioners 21 .…”

Intradermal Injection of Hybrid Complexes of High- and Low-Molecular-Weight Hyaluronan: Where Do We Stand and Where Are We Headed in Regenerative Medicine?

“…Despite the lack of chemical modification, HCCs showed a significantly higher resistance to hyaluronidase action than H-HA in vitro [ 19 ]; additionally, in vivo murine studies employing high-frequency ultrasound showed that HCCs remained detectable for 10 weeks (32 mg/mL), and up to 29 weeks for higher molar concentrations (45 mg/mL), exhibiting a slow volumetric degradation, similar to that of chemically crosslinked gel [ 20 ]. The correlation between in vivo permanence data with in vitro enzymatic degradation results shows that HCCs at 45 mg/mL evidence a comparable duration in vivo with respect to the cross-linked HA 25 mg/mL filler (29 weeks vs. 33 weeks, respectively).…”

“…The correlation between in vivo permanence data with in vitro enzymatic degradation results shows that HCCs at 45 mg/mL evidence a comparable duration in vivo with respect to the cross-linked HA 25 mg/mL filler (29 weeks vs. 33 weeks, respectively). However, at the same time, interestingly, degradability by hyaluronidase was enhanced, mainly at the early stage of the in vitro kinetics study [ 20 ]. At 45 mg/mL, HCCs only had freely soluble HA in them, and during the in vitro degradation study, the average molecular weight kept decreasing.…”

“…On the other hand, cross-linked HA 25 mg/mL, according to its cross-linked nature, contained around 13% of the soluble HA fraction. During enzymatic degradation, its soluble fraction increased up to 70–74%, reaching a plateau after 1 h. Only once the soluble fraction plateau was reached did the average molecular weight begin to decrease [ 20 ]. For its elastic and viscous moduli, HCCs at 45 mg/mL retained around 77% and 87% of their initial values after 5 min of incubation, while H-HAs only retained 50% and 68% of their initial values.…”