Influence of Injectable Hyaluronic Gel System on Skin Microbiota, Skin Defense Mechanisms and Integrity (Ex vivo Study).

Abstract

Objective: The influence of injectable hyaluronic gels on skin's microbiota is unclear. As well, skin microbiota is a key factor modulating final effect of injectable gels. The ex-vivo study was aimed at alterations following hyaluronic acid injection into the dermis in non-sterile skin surface conditions.

Methods: Ex vivo human skin explants in the presence or absence of either S. epidermidis or S. aureus, were treated with either control excipient (0.9% sodium chloride) or test product (Hyaluronic acid injectable S, HA-S). Bacterial analysis was performed, as well as skin structural integrity. Histological imaging and immunostaining analysis in the presence of skin markers: epidermal (CD1a, Toll-like receptor 2 (TLR2), Beta-defensin-3 (BD3), CCN1) and dermal (DC-SIGN, Decorin) were then performed.

Results: The injection of control excipient E and test product P, both associated with bacterial deposits, induced similar noticeable increase of S. epidermidis growth over 4 days, but no noticeable effect on growth of S. aureus. The injection of control excipient, associated with bacterial deposits, showed epidermal and dermal alterations increased with time. It was observed significant increase of epidermal CD1a, TLR2, CCN1 and dermal DC-SIGN, Decorin on Day 2. The injection of test product, associated with bacterial deposits, in contrast to injection of control excipient, associated with bacterial deposits, induced very slight but significant improvement of epidermal viability as well as significant decrease of epidermal TLR2, BD3, CCN1 and dermal DC-SIGN on Day 2.

Conclusion: Our investigation showed that both intradermal injections, HA-based solution or control excipient, trigger short-term skin microbiota growth. We indicate strong influence of non-sterile skin surface conditions on human skin explant viability when skin barrier damaged by injection puncture and highlights differences of epidermal/dermal response depended on injected composition.