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Figure 2: (A) Filler injections after radiofrequency (RF) treatment results in volumization. N: normal; F: Glytone 3 filler injection; RF30s+F: RF treatment
         for 30 s, RF60s+F: RF treatment for 60 s, both before filler injections through tunneling method; T+F: filler injected after tunneling without RF treatment
         for 30 s. (B) “*” sign indicates areas injected with fillers. Extracellular matrix components stained with Masson's trichrome show the treatment with both
         filler and RF enhances collagen bundle deposition (blue) and fibroplasia (red) Dermis stained with Verhoeff-Van Gieson shows that RF treatment resulted in
         shorter elastin fibers (“arrow” sign). Image used with permission. [3]
         pain) were observed in 93.5%  of Restylane®-treated sites   stimulates the production of new collagen in human skin. In
         and 90.6% of Zyplast®-treated sites, and lasted for 7 days at   this study, each of 11 volunteers received 3 filler injections
         most. Reactions were also observed after 14 days or more   into one forearm and 3 isotonic saline vehicle injections
         in 12 patients, with 10 reactions in Restylane®-treated sites   into the contralateral forearm. Tissue biopsies results taken
         and 11 reactions in Zyplast®-treated sites. Local erythema   4 and 13 weeks after injection revealed increased collagen
         was the most common delayed reaction. All reactions   deposition around the filler, higher type I procollagen
         spontaneously subsided without treatment  and were  not   marker staining, upregulation of type I and II procollagen
         considered to be hypersensitivity reactions. A similar study   expression, and elongated fibroblast morphology at the
         was conducted comparing three  formulations of HA filler   injection site. Various mechanisms have been proposed in
         (Juvederm 30™, Juvederm Ultra™ and Juvederm Ultra Plus™;   an  attempt  to  elucidate the  de novo  collagen production,
         Allergan) with Zyplast® for the treatment of nasolabial   including mechanical fibroblast stretching, growth factor
         folds. This study also concluded that the effect of HA fillers   stimulation, and inhibition  of collagen  degradation.
         was much longer-lasting than that of bovine collagen. [16]  Inhibition  of collagen degradation  was  proposed after
                                                             observing the expression of matrix metalloproteinases and
         A Scandinavian double-blinded, randomized, longitudinal   their regulators in skin treated using NASHA. [27]
         comparison study with 68 patients was conducted between
         Perlane® (a form of NASHA produced by Medicis Aesthetics,   Double-blinded, randomized studies have also been
         Scottsdale, AZ,  USA) and Zyplast®  for the  treatment  of   conducted  with Hylaform® (Inamed Aesthetics), an FDA-
         nasolabial folds.  Using the GAIS rating, both showed   approved HA that is extracted from rooster combs. Hylaform®
                       [26]
         “much or very much improved” effects (89.7% for Perlane®   had similar efficacy compared to Zyplast® for up to 4 months
         and 86.8% for Zyplast®) at the baseline period (2 weeks after   in 300 patients treated for nasolabial folds, with few adverse
         injection). Perlane® consistently had higher WSRS ratings   effects and no allergic reactions.  A small randomized
                                                                                          [28]
         during the 9-month follow-up period. Reactions were found   longitudinal study was also conducted with Hylaform Plus®,
         at the injection sites for both (17.6% for Perlane® and 30.9%   which contains bigger cross-linked molecules with a larger
         for Zyplast®). Three patients showed delayed reactions but   average particle size than its Hylaform® counterpart. The
         none were considered to be hypersensitivity reactions.  study was conducted in comparison to Restylane® for the
                                                             treatment of nasolabial folds and examiners were blinded
         A recent study regarding the use of NASHA showed that it   during  evaluation.  At  3,  4.5, and 6 months,  Restylane®
         76                                                                         Plast Aesthet Res || Vol 3 || Mar 23, 2016
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