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Page 2 of 8                                 Bon Betemps et al. Plast Aesthet Res 2018;5:19  I  http://dx.doi.org/10.20517/2347-9264.2018.24

               INTRODUCTION
               Hyaluronic acid (HA) fillers are recognized as the gold standard in aesthetic medicine to treat signs of facial
               ageing; i.e. for filling wrinkles and skin depressions, and to shape the volume of the face . In 2016, according to
                                                                                       [1]
               the American Society for Aesthetic Plastic Surgery (ASAPS), 2.49 million HA filler treatments were performed
               in the United States of America only with a high growth of 16.1% versus the previous year . Since the market
                                                                                          [2]
               launch of Juvéderm Voluma (Allergan, Pringy, France) in 2010, the first HA volumizer and current world market
               leader in this segment, there has been a growing interest from physicians for HA fillers with a high ability to
               project the skin tissues . Juvéderm Voluma is produced thanks to the VYCROSS proprietary technology .
                                   [3]
                                                                                                        [4]
               This technology uses a combination of low and high molecular weights of HA during the crosslinking to
               improve the efficacy of the chemical reaction. Recently, a novel proprietary manufacturing technology for the
               production of innovative HA fillers has been discovered. It is the OXIFREE technology (Kylane Laboratoires,
               Geneva, Switzerland) which is characterized by the extraction of destructive oxygen during the manufacturing
               process, including during the crosslinking step, to significantly preserve the intrinsic properties of the high
               molecular weight of HA chains. This new technology provides HA fillers with advanced rheological properties
               which makes it possible to exhibit strong projection capacities and therefore a high ability to restore the volume
               of the facial skin tissues. Volumizer products such as Juvéderm Voluma or the HA fillers benefiting from the
               OXIFREE technology are designed by the manufacturers to be injected into the subcutaneous tissues and the
               supraperiostic zone. For these products, high projection capacity is thus required to efficiently treat the areas of
               the face for which the creation of volume is necessary such as the cheeks, cheekbones, chin, temples and jawlines.
               Rheological properties are also naturally considered by the manufacturers to design their products because
                                                                                                  [5-7]
               these properties have an essential importance on the mechanical behavior of the HA gel in the tissues . Many
               publications have been published on this topic over the past few years and some of them have highlighted the
               key role of the normal force F  for the tissue projection of the HA fillers [8-11] . In this publication, a new skin
                                        N
               model assay is proposed to assess the projection capacity of the HA fillers. This assay is applied on Juvéderm
               Voluma, the market leader in the segment of the volumizers, and a new HA filler benefiting from the OXIFREE
               technology, to compare the projection capacities of these products. The results obtained with this skin model
               assay are then discussed, with special consideration of the key rheological characteristics of these two products.



               METHODS
               Two crosslinked HA fillers intended for facial injection in aesthetic medicine were subjected to flow,
               oscillatory shear-stress and compression tests with a DHR-1 rheometer (TA Instruments, New Castle, USA).
               Among these two HA fillers presented in Table 1, one is manufactured according to the novel OXIFREE
               technology and one is Juvéderm Voluma (Allergan, Pringy, France), manufactured according to the
               VYCROSS technology.

               The two crosslinked HA fillers are studied in terms of rheological properties and also with the new skin
               model assay.


               Rheological characterization
               Flow test
               The flow test enables the measurement of the viscosity η of the gel. It was performed at a temperature of 25 °C
               under shear rate from 0.001 to 1000 s  with a cone/plate aluminium geometry of 40 mm 2 degrees and a
                                               -1
               50-µm gap between the cone and the plate of the rheometer. The value of the viscosity η is measured at the
               shear rate of 1 s .
                            -1

               Oscillatory shear stress test
               The oscillatory shear stress test enables the measurement of the elastic modulus G’. It was performed at a
               temperature of 25 °C in shear stress oscillation mode at 1.0% of strain, within the linear viscoelastic region,
               with a cone/plate aluminium geometry of 40 mm 2 degrees and a 50-µm gap between the cone and the plate
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