Biological Effects of Hyaluronic Acid-Based Dermal Fillers and Laser Therapy on Human Skin Models

September 2020 | Volume 19 | Issue 9 | Features | 897 | Copyright © September 2020


Published online August 24, 2020

doi:10.36849/JDD.2020.4856

Laura Huth PhD,a Yvonne Marquardt,a Ruth Heise PhD,a Katharina Fietkau,a Jens Malte Baron MD,a,b*, Sebastian Huth PhDa*

aDepartment of Dermatology and Allergology, Medical Faculty, RWTH Aachen University, Aachen, Germany bInterdisciplinary Center for Laser Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany

*Sebastian Huth and Jens Malte Baron contributed equally to this work.

Abstract
Injection of dermal fillers is one of the most frequently performed aesthetic procedures. The aim of the present study was to investigate the biological effects of different stabilized hyaluronan (HA) and poly-l-lactic acid fillers with and without subsequent additional fractional laser co-treatment on skin morphology and gene expression. Intradermal injection resulted in a significant enhancement of epidermal thickness detected by histological analysis. Combining HA fillers with ablative fractional CO2- or Er:YAG laser irradiation enhanced this effect. Gene expression profiling revealed an upregulation of modulators of tissue remodeling (eg TIMP3, SERPIN E1) and collagens (COL11A1). On the other hand, we detected a downregulation of differentiation markers (eg FLG, LOR, KRT1) and proinflammatory cytokines (eg IL-36, IL-1β). Interestingly, HA-based fillers revealed a specific upregulation pattern of chemokines such as CXCL5 andCCL20 suggesting a secondary effect of these fillers on the immune cells of the skin, especially monocytes and macrophages.

Taken together, our data show enhancing effects of dermal fillers on epidermal thickness and prove the proliferating effects of these products on epidermal cells on the molecular level. Moreover, our findings reveal synergistic effects of fractional ablative laser treatment and HA dermal filler injection suggesting a combination of both treatments.

J Drugs Dermatol. 2020;19(9):897-899. doi:10.36849/JDD.2020.4856

INTRODUCTION

Injection of hyaluronic acid (HA) dermal fillers is one of the most frequently performed aesthetic procedures.1 HA fillers exist in many different formulations differing in HA concentration, particle size and cross-linking density. While HA fillers with high-density and large particles are recommended for deep dermal injections, fillers with low-density and small particles are more commonly used for fine lines.1

The direct biological effects of dermal fillers monotherapy and combination therapy with ablative fractional CO2- or Er:YAG laser irradiation on human skin cells are not completely understood. Organotypic three-dimensional (3D) skin equivalents have been established for standardized studies of the human skin.2 The aim of the present study was to investigate the molecular effects of different stabilized HA and poly-l-lactic acid (PLLA)-based fillers with and without subsequent additional fractional laser co-treatment.

MATERIALS AND METHODS

In this comparative effectiveness research in vitro study different stabilized HA (Restylane Skinboosters Vital (HA1) and Vital Light (HA2) as well as Refyne (HA3)) and PLLA-based (Sculptra) fillers were injected intradermally into skin models as a monotherapy and in combination with ablative fractional CO2- or Er:YAG laser irradiation. Effects on skin morphology were assessed immediately after treatment and 5 days later by histological analysis. In addition, a transcriptomic gene expression profiling was performed on day 5 after treatment. Statistical analysis was performed using the Mann-Whitney U test. Values of P<0.05 were considered statistically significant.

RESULTS

Intradermal injection of the different fillers into skin models resulted in a significant enhancement of epidermal thickness detected by histological analysis (Figures 1A and 1B). On the molecular level, gene expression profiling by microarray analyses revealed an upregulation of modulators of tissue remodeling (eg, TIMP3, SERPIN E1) and collagens (COL11A1) on day 5 after injection of the different fillers (Figures 1C–E). On the other hand, we detected a downregulation of differentiation markers (eg, FLG, LOR, KRT1) and proinflammatory cytokines (eg, IL-36, IL-1β). Combining HA dermal fillers with ablativefractional CO2- or Er:YAG laser irradiation enhanced the effect of epidermal thickening (Figures 2A and 2B). Gene expression profiling of the combined treatment revealed an upregulation
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