Improvements in Skin Quality Biological Markers in Skin Explants Using Hyaluronic Acid Filler VYC-12L

Lauren Nakab, Christopher K Hee, Olivier Guetta, Lauren Nakab, Christopher K Hee, Olivier Guetta

Abstract

Hyaluronic acid (HA), both crosslinked and uncrosslinked, is used clinically to treat fine lines and provides additional improvements in skin quality attributes. The purpose of this study was to assess potential early differences in the expression of biological markers of skin quality in living human skin explants injected with uncrosslinked and crosslinked HA gels.

Methods: Living human skin explants injected with VYC-12L or noncrosslinked HA with mannitol (HYD) and noninjected controls were assessed via microscopy, histology, and immunohistochemistry on days 3 and/or 8 for biological markers of elasticity (collagen density, elastin, fibrillin-1) and hydration [aquaporin-3, acidic glycosaminoglycans (GAGs), HA]. Hydration was also assessed via a corneometer probe on days 0, 1, 2, and 8.

Results: On day 3 versus controls, VYC-12L moderately increased collagen density in the upper reticular dermis and clearly increased fibrillin-1 expression, with slight increases persisting on day 8. Increases with HYD were smaller and did not persist on day 8. Both VYC-12L and HYD increased aquaporin-3 expression and GAG content on days 3 and 8, but VYC-12L produced greater GAG increases in the reticular dermis. Day 8 instrument-assessed hydration increased by 49% and 22% for VYC-12L and HYD, respectively. Elastin expression in oxytalan and elaunin fibers was unchanged. Upper-dermal HA reductions suggested HA injection-induced hyaluronidase expression.

Conclusion: VYC-12L produced greater, more lasting improvements in biological markers of skin quality than HYD.

Conflict of interest statement

Disclosure: L. Nakab, C.K. Hee, and O. Guetta are employees of Allergan plc and may own stock/stock options in the company. This study was funded by Allergan plc, Dublin, Ireland. Medical writing support for this article was provided at the request of the authors by Regina Kelly of Peloton Advantage, LLC, an OPEN Health company, Parsippany, New Jersey, and was funded by Allergan plc. The opinions expressed in this article are those of the authors. The authors received no honorarium/fee or other forms of financial support related to the development of this article.

Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.

Figures

Fig. 1.
Fig. 1.
Eleven-millimeter round human skin explants in BIO-EC survival culture medium. Image courtesy of Laboratoire BIO-EC, Longjumeau, France.
Fig. 2.
Fig. 2.
Microscopic observation of changes in collagen density on days 3 and 8 after injection. Increases in the density of the collagen network are observed following VYC-12L and HYD treatment in the papillary and upper reticular dermis by the heightened intensity of green staining as compared with control. Improvements in the relief of the dermal–epidermal junction may be seen with VYC-12L (arrow). HYD, noncrosslinked hyaluronic acid with mannitol; VYC-12L, crosslinked hyaluronic acid injectable gel with lidocaine.
Fig. 3.
Fig. 3.
Microscopic observation of changes in fibrillin-1 expression on days 3 and 8 after injection. The increase in fibrillin-1 expression in the papillary dermis is shown following VYC-12L and HYD treatment as enhanced green immunofluorescence as compared with control. Nuclei are counterstained in red. HYD, noncrosslinked hyaluronic acid with mannitol; VYC-12L, crosslinked hyaluronic acid injectable gel with lidocaine.
Fig. 4.
Fig. 4.
Microscopic observation of changes in AQP3 expression on days 3 and 8 after injection. The increase in AQP3 expression in the epidermis (basal layer of keratinocyte) is shown as an enhanced intensity of immunostaining (pink). AQP3, aquaporin-3; HYD, noncrosslinked hyaluronic acid with mannitol; VYC-12L, crosslinked hyaluronic acid injectable gel with lidocaine.
Fig. 5.
Fig. 5.
Microscopic observation of changes in GAG content on days 3 and 8 after injection. The increase in acidic GAG expression in the papillary dermis and upper reticular dermis is shown as an enhanced intensity of blue staining. GAG, glycosaminoglican; HYD, noncrosslinked hyaluronic acid with mannitol; VYC-12L, crosslinked hyaluronic acid injectable gel with lidocaine.
Fig. 6.
Fig. 6.
Change from baseline in corneometric hydration values on days 1, 2, and 8 after injection. HYD, noncrosslinked hyaluronic acid with mannitol; VYC-12L, crosslinked hyaluronic acid injectable gel with lidocaine. *P <0.05 vs control and HYD. †P <0.05 vs control.

References

    1. Rittié L, Fisher GJ. Natural and sun-induced aging of human skin. Cold Spring Harb Perspect Med. 2015;5:a015370.
    1. Trojahn C, Dobos G, Lichterfeld A, et al. Characterizing facial skin ageing in humans: disentangling extrinsic from intrinsic biological phenomena. Biomed Res Int. 2015;2015:318586.
    1. Lee DH, Oh JH, Chung JH. Glycosaminoglycan and proteoglycan in skin aging. J Dermatol Sci. 2016;83:174–181.
    1. Lapière CM. The ageing dermis: the main cause for the appearance of ‘old’ skin. Br J Dermatol. 1990;122suppl 355–11.
    1. Mellem D, Sattler M, Pagel-Wolff S, et al. Fragmentation of the mitochondrial network in skin in vivo. PLoS One. 2017;12:e0174469.
    1. Langton AK, Sherratt MJ, Griffiths CE, et al. A new wrinkle on old skin: the role of elastic fibres in skin ageing. Int J Cosmet Sci. 2010;32:330–339.
    1. Waller JM, Maibach HI. Age and skin structure and function, a quantitative approach (II): protein, glycosaminoglycan, water, and lipid content and structure. Skin Res Technol. 2006;12:145–154.
    1. Giacomoni PU, Rein G. A mechanistic model for the aging of human skin. Micron. 2004;35:179–184.
    1. Nkengne A, Bertin C. Aging and facial changes–documenting clinical signs, part 1: clinical changes of the aging face. Skinmed. 2013;11:281–286.
    1. Choi JW, Kwon SH, Huh CH, et al. The influences of skin visco-elasticity, hydration level and aging on the formation of wrinkles: a comprehensive and objective approach. Skin Res Technol. 2013;19:e349–e355.
    1. Berardesca E, Cameli N, Primavera G, et al. Clinical and instrumental evaluation of skin improvement after treatment with a new 50% pyruvic acid peel. Dermatol Surg. 2006;32:526–531.
    1. Taieb M, Gay C, Sebban S, et al. Hyaluronic acid plus mannitol treatment for improved skin hydration and elasticity. J Cosmet Dermatol. 2012;11:87–92.
    1. Sundaram H, Cegielska A, Wojciechowska A, et al. Prospective, randomized, investigator-blinded, split-face evaluation of a topical crosslinked hyaluronic acid serum for post-procedural improvement of skin quality and biomechanical attributes. J Drugs Dermatol. 2018;17:442–450.
    1. Bukhari SNA, Roswandi NL, Waqas M, et al. Hyaluronic acid, a promising skin rejuvenating biomedicine: a review of recent updates and pre-clinical and clinical investigations on cosmetic and nutricosmetic effects. Int J Biol Macromol. 2018;120pt B1682–1695.
    1. Kogan G, Soltes L, Stern R, et al. Pethrick RA, Ballada A, Zaikov GE. Hyaluronic acid: a biopolymer with versatile physico-chemical and biological properties. In: Handbook of Polymer Research: Monomers, Oligomers, Polymers and Composites. 2007Hauppauge, NY: Nova Science Publishers, Inc; 393–439.
    1. Yoshida H, Komiya A, Ohtsuki R, et al. Relationship of hyaluronan and HYBID (KIAA1199) expression with roughness parameters of photoaged skin in caucasian women. Skin Res Technol. 2018;24:562–569.
    1. Niforos F, Acquilla R, Ogilvie P, et al. A prospective, open-label study of hyaluronic acid-based filler with lidocaine (VYC-15L) treatment for the correction of infraorbital skin depressions. Dermatol Surg. 2017;43:1271–1280.
    1. Landau M, Fagien S. Science of hyaluronic acid beyond filling: fibroblasts and their response to the extracellular matrix. Plast Reconstr Surg. 2015;1365 suppl188S–195S.
    1. Juvederm Volite B [direction for use]. 2017Pringy, France: Allergan.
    1. Juvederm Hydrate [EU Direction for Use]. 2016Pringy, France: Allergan.
    1. Abreu EL, Palmer MP, Murray MM. Collagen density significantly affects the functional properties of an engineered provisional scaffold. J Biomed Mater Res A. 2010;93:150–157.
    1. Wunsch A, Matuschka K. A controlled trial to determine the efficacy of red and near-infrared light treatment in patient satisfaction, reduction of fine lines, wrinkles, skin roughness, and intradermal collagen density increase. Photomed Laser Surg. 2014;32:93–100.
    1. Baldwin AK, Simpson A, Steer R, et al. Elastic fibres in health and disease. Expert Rev Mol Med. 2013;15:e8.
    1. Bensouilah J, Buck P. Bensouilah J, Buck P. Skin structure and function. In: Aromadermatology: Aromatherapy in the Treatment and Care of Common Skin Conditions. 2006Abingdon, United Kingdom: Radcliffe Publishing; 1–11.
    1. Xing F, Liao W, Jiang P, et al. Effect of retinoic acid on aquaporin 3 expression in keratinocytes. Genet Mol Res. 2016;15:15016951.
    1. Li J, Tang H, Hu X, et al. Aquaporin-3 gene and protein expression in sun-protected human skin decreases with skin ageing. Australas J Dermatol. 2010;51:106–112.
    1. Le Fur I, Reinberg A, Lopez S, et al. Analysis of circadian and ultradian rhythms of skin surface properties of face and forearm of healthy women. J Invest Dermatol. 2001;117:718–724.
    1. Matsumoto T, Yuasa H, Kai R, et al. Skin capacitance in normal and atopic infants, and effects of moisturizers on atopic skin. J Dermatol. 2007;34:447–450.
    1. Sundaram H, Rohrich RJ, Liew S, et al. Cohesivity of hyaluronic acid fillers: development and clinical implications of a novel assay, pilot validation with a five-point grading scale, and evaluation of six U.S. Food and drug administration-approved fillers. Plast Reconstr Surg. 2015;136:678–686.
    1. Sundaram H, Cassuto D. Biophysical characteristics of hyaluronic acid soft-tissue fillers and their relevance to aesthetic applications. Plast Reconstr Surg. 2013;1324 suppl 25S–21S.
    1. Gavard Molliard S, Albert S, Mondon K. Key importance of compression properties in the biophysical characteristics of hyaluronic acid soft-tissue fillers. J Mech Behav Biomed Mater. 2016;61:290–298.
    1. Gavard Molliard S, Bon Betemps J, Hadjab B, et al. Key rheological properties of hyaluronic acid fillers: from tissue integration to product degradation. Plast Aesthet Res. 2018;5:17.
    1. La Gatta A, Salzillo R, Catalano C, et al. Hyaluronan-based hydrogels as dermal fillers: the biophysical properties that translate into a “volumetric” effect. PLoS One. 2019;14:e0218287.
    1. Burgher F, Mathieu L, Lati E, et al. Experimental 70% hydrofluoric acid burns: histological observations in an established human skin explants ex vivo model. Cutan Ocul Toxicol. 2011;30:100–107.
    1. Sundaram H, Mackiewicz N, Burton E, et al. Pilot comparative study of the topical action of a novel, crosslinked resilient hyaluronic acid on skin hydration and barrier function in a dynamic, three-dimensional human explant model. J Drugs Dermatol. 2016;15:434–441.
    1. Lebonvallet N, Jeanmaire C, Danoux L, et al. The evolution and use of skin explants: potential and limitations for dermatological research. Eur J Dermatol. 2010;20:671–684.
    1. Park GH, Chang SE, Bang S, et al. Usefulness of skin explants for histologic analysis after fractional photothermolysis. Ann Dermatol. 2015;27:283–290.
    1. Shapiro SD, Endicott SK, Province MA, et al. Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon. J Clin Invest. 1991;87:1828–1834.
    1. Haydont V, Bernard BA, Fortunel NO. Age-related evolutions of the dermis: clinical signs, fibroblast and extracellular matrix dynamics. Mech Ageing Dev. 2019;177:150–156.
    1. Quan T, Wang F, Shao Y, et al. Enhancing structural support of the dermal microenvironment activates fibroblasts, endothelial cells, and keratinocytes in aged human skin in vivo. J Invest Dermatol. 2013;133:658–667.
    1. Paliwal S, Fagien S, Sun X, et al. Skin extracellular matrix stimulation following injection of a hyaluronic acid-based dermal filler in a rat model. Plast Reconstr Surg. 2014;134:1224–1233.
    1. Niforos F, Ogilvie P, Cavallini M, et al. VYC-12 injectable gel is safe and effective for improvement of facial skin topography: a prospective study. Clin Cosmet Investig Dermatol. 2019;12:791–798.
    1. Borrell M, Leslie DB, Tezel A. Lift capabilities of hyaluronic acid fillers. J Cosmet Laser Ther. 2011;13:21–27.
    1. Eccleston D, Murphy DK. Juvéderm Volbella in the perioral area: a 12-month prospective, multicenter, open-label study. Clin Cosmet Investig Dermatol. 2012;5:167–172.
    1. Sattler G, Philipp-Dormston WG, Van Den Elzen H, et al. A prospective, open-label, observational, postmarket study evaluating VYC-17.5L for the correction of moderate to severe nasolabial folds over 12 months. Dermatol Surg. 2017;43:238–245.
    1. Monheit G, Beer K, Hardas B, et al. Safety and effectiveness of the hyaluronic acid dermal filler VYC-17.5L for nasolabial folds: results of a randomized, controlled study. Dermatol Surg. 2018;44:670–678.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する