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

April 2016 | Volume 15 | Issue 4 | Original Article | 434 | Copyright © April 2016

Hema Sundaram MD,a Nicolas Mackiewicz PhD,b Emeline Burton MSc,b Laurent Peno-Mazzarino BSc,c Elian Lati PhD,c and Stéphane Meunier PhDb

aDermatology, Cosmetic & Laser Surgery, Rockville, MD
bTeoxane SA, R&D Department, Geneva, Switzerland
cLaboratoire BIO-EC, Longjumeau, France

BACKGROUND: Hyaluronic acid (HA) is a popular ingredient in topical formulations for cosmetic improvement of the skin. Most formulations contain linear, non-crosslinked HA oligomers, low molecular weight (LMW) HA, and/or high molecular weight (HMW) HA. Crosslinking of HA enhances its clinical longevity and mechanical characteristics. The objective of this study was to characterize the topical effects of a new, crosslinked resilient HA (RHA) that is also available as a cohesive, tissue-integrating injectable filler, compared with non-crosslinked HMW HA and LMW HA. Living human skin explants that preserve the 3-dimensional structure of in vivo skin were used to maximize clinical relevance.
METHODS: Standardized doses of each HA product were applied daily for 9 days to human skin explant surfaces. Untreated explants served as controls. Water content of the stratum corneum and entire epidermis was analyzed by Raman spectroscopy. Transepidermal water loss (TEWL) was measured to assess skin barrier function. Explant morphology and microrelief were evaluated by optical and scanning electron microscopy.
RESULTS: Crosslinked RHA achieved a significant increase in epidermal water content (7.6%) over the control. Spectral cartography confirmed a higher epidermal water content with RHA than with HMW HA or LMW HA. TEWL was reduced by 27.8% with RHA, and by 15.6% with HMW HA, but increased by 55.5% with LMW HA. Cutaneous microrelief improved with RHA. Corneocyte cohesion improved with RHA and HMW HA.
CONCLUSIONS: This comparative, multimodal study demonstrated greater benefits of topical crosslinked RHA over linear HMW HA or LMW HA in reducing TEWL, retaining and redistributing water within the epidermis, maintaining skin integrity, and improving skin barrier structure and function. RHA was a more efficacious humectant than LMW HA, and a more efficacious occlusive moisturizer than HMW HA. These integrative epidermal repair activities are of significant value for addressing primary deficits of aging skin, improving tolerance to retinoids and other topical agents, and optimizing procedural outcomes. A combination of topical and injectable HA provides an elegant model of synergistic, multi-level skin restoration.

J Drugs Dermatol. 2016;15(4):434-441.


Water is essential for the normal structure and functioning of the skin. There is precise homeostatic regulation of water content within different skin layers. The stratum corneum is a hydrophobic layer containing dead cells, while the underlying, viable epidermis is a living, hydrophilic layer. It is this discontinuity that isolates the stratum corneum structurally and helps to maintain a high water content in the viable epidermis.1 In normal, healthy skin, the water content of the stratum corneum is markedly lower than in the viable epidermis (15%-30% vs 70%).2 Water content of the skin influences various critical characteristics including barrier function, elasticity, and electrical resistance, and hence determines its overall appearance.
Water can reach the skin surface actively through sweat ducts or passively through diffusion across the epidermis. The latter process, known as transepidermal water loss (TEWL), is a sensitive indicator of the integrity of the stratum corneum.3 TEWL is inversely proportional to skin barrier function. TEWL is relatively low in healthy skin. The main barrier to the passage of water and other molecules across the stratum corneum is the extracellular lipid bilayer matrix, within which corneocytes are embedded. In addition to lipids, the extracellular matrix also contains enzymes, structural proteins, and antimicrobial peptides that impact barrier function.4-7
As skin ages, its barrier function becomes compromised. Reduction in intrinsic moisturizing factors and lipids in the stratum