Prospective, Randomized, Investigator-Blinded, Split-Face Evaluation of a Topical Crosslinked Hyaluronic Acid Serum for Post-Procedural Improvement of Skin Quality and Biomechanical Attributes

April 2018 | Volume 17 | Issue 4 | Original Article | 442 | Copyright © April 2018

Hema Sundaram MD FAAD,a Angnieszka Cegielska MD,b Agnieszka Wojciechowska,b and Patrice Delobel PhDc

aDermatology, Cosmetic & Laser Surgery, Rockville, MD bDermscan, Gdansk, Poland cTeoxane SA, Geneva, Switzerland

Background: This split-face, controlled study investigated the ability of a topical crosslinked hyaluronic acid formulation (RHA serum) to enhance clinical results from fillers, microneedling, or chemical peeling of aging skin. Previous comparative skin explant studies demonstrated greater efficacy of RHA serum than topical non-crosslinked high or low molecular weight hyaluronic acid in decreasing trans-epidermal water loss, increasing epidermal hydration, and improving corneocyte microstructure. Methods: 24 female subjects aged 35 to 55 were enrolled. 8 received intradermal hyaluronic acid filler injection, 8 received microneedling, and 8 received superficial mandelic acid chemical peeling. Subjects initiated twice-daily, standardized application of RHA serum to one side of the face 2 days after the procedure. Topographical imaging, bioinstrumental, and blinded clinical evaluations were performed at days 0, 14, and 28. Results: Areas treated with RHA serum showed statistically significant improvements in skin surface topography and hydration compared to untreated areas. Blinded investigator scoring showed greater improvement of RHA serum-treated skin in moisture, tone/complexion, radiance, texture, uniformity, and global appearance. Subjects’ questionnaire responses correlated with these findings. Subjects expressed greater satisfaction with appearance of the treated hemiface. No adverse events were observed during the study. Conclusions: When initiated post-procedurally, topical RHA serum was well-tolerated and enhanced biomechanical properties, quality, and clinical appearance of the skin. Based on these data, RHA serum may be of value in improving patient outcomes and satisfaction following minimally invasive aesthetic procedures. The availability of the same hyaluronic acid technology also as a cohesive, tissue-integrating injectable filler enables synergistic, multi-level treatment plans to be devised.

J Drugs Dermatol. 2018;17(4):442-450.


Hyaluronic acid (HA), a glycosaminoglycan that occurs naturally in the skin, remains a perennially popular constituent of topical cosmetic formulations and injectable soft tissue fillers. HA has excellent safety and tolerability profiles; it is reported to be non-toxic, non-immunogenic and non-carcinogenic, and to have low sensitization potential.1,2 Over the past two decades, variations in HA molecular weight, concentration, and crosslinking have given rise to an extensive repertoire of products with different biophysical properties.2-5 The therapeutic properties of non-crosslinked HA in topical formulations have been attributed primarily to the moisturizing effect of the molecule, which can attract and bind one thousand times its weight in water.6 In contrast, injectable HA fillers are crosslinked to improve their durability and mechanical properties, and their injection into the dermis or subcutis elicits other effects besides hydration, leading to improvement in tissue quality and allowing the treatment of age-related rhytides and volume loss.7-9 Non-crosslinked HA in topical formulations ranges from oligomers and low molecular weight (LMW) HA to high molecular weight (HMW) HA.10 To date, topical formulations of crosslinked HA have been uncommon. The rationale behind use of non-crosslinked HMW and LMW HA for skincare products includes their cosmetic properties, and their presumed skin penetrability.11-14 However, few controlled trials have assessed the efficacy of these formulations, and there is controversy about the ability of HA to access the dermis through the stratum corneum.10,11,14 Generally, HA molecules heavier than 100 kDa have limited capacity to penetrate the epidermis. It has been suggested that topical application of HMW-HA might benefit the skin by forming a surface film to protect the stratum corneum, thus creating a barrier to water loss.10 The aim of this study was to investigate the ability of a recently developed topical crosslinked HA formulation, resilient