Skin Cell and Tissue Responses to Cross-Linked Hyaluronic Acid in Low-Grade Inflammatory Conditions

Hyaluronic acid (HA), used in a variety of medical applications, is associated in rare instances to long-term adverse effects. Although the aetiology of these events is unknown, a number of hypotheses have been proposed, including low molecular weight of HA (LMW-HA) in the filler products. We hypoth...

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Main Authors: Benjamin Sanchez, Sandra Ferraro, Audrey Josset-Lamaugarny, Aurélie Pagnon, Charlie K. Hee, Lauren Nakab, Dominique Sigaudo-Roussel, Bérengère Fromy
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:International Journal of Inflammation
Online Access:http://dx.doi.org/10.1155/2023/3001080
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author Benjamin Sanchez
Sandra Ferraro
Audrey Josset-Lamaugarny
Aurélie Pagnon
Charlie K. Hee
Lauren Nakab
Dominique Sigaudo-Roussel
Bérengère Fromy
author_facet Benjamin Sanchez
Sandra Ferraro
Audrey Josset-Lamaugarny
Aurélie Pagnon
Charlie K. Hee
Lauren Nakab
Dominique Sigaudo-Roussel
Bérengère Fromy
author_sort Benjamin Sanchez
collection DOAJ
description Hyaluronic acid (HA), used in a variety of medical applications, is associated in rare instances to long-term adverse effects. Although the aetiology of these events is unknown, a number of hypotheses have been proposed, including low molecular weight of HA (LMW-HA) in the filler products. We hypothesized that cross-linked HA and its degradation products, in a low-grade inflammatory microenvironment, could impact immune responses that could affect cell behaviours in the dermis. Using two different cross-linking technologies VYC-15L and HYC-24L+, and their hyaluronidase-induced degradation products, we observed for nondegraded HA, VYC-15L and HYC-24L+, a moderate and transient increase in IL-1β, TNF-α in M1 macrophages under low-grade inflammatory conditions. Endothelial cells and fibroblasts were preconditioned using inflammatory medium produced by M1 macrophages. 24 h after LMW-HA fragments and HA stimulation, no cytokine was released in these preconditioned cells. To further characterize HA responses, we used a novel in vivo murine model exhibiting a systemic low-grade inflammatory phenotype. The intradermal injection of VYC-15L and its degradation products induced an inflammation and cell infiltration into the skin that was more pronounced than those by HYC-24L+. This acute cutaneous inflammation was likely due to mechanical effects due to filler injection and tissue integration rather than its biological effects on inflammation. VYC-15L and its degradation product potentiated microvascular response to acetylcholine in the presence of a low-grade inflammation. The different responses with 2D cell models and mouse model using the two tested cross-linking HA technologies showed the importance to use integrative complex model to better understand the effects of HA products according to inflammatory state.
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spelling doaj-art-6d4cea07a75d4e06afd09db634be387a2025-02-03T06:43:16ZengWileyInternational Journal of Inflammation2042-00992023-01-01202310.1155/2023/3001080Skin Cell and Tissue Responses to Cross-Linked Hyaluronic Acid in Low-Grade Inflammatory ConditionsBenjamin Sanchez0Sandra Ferraro1Audrey Josset-Lamaugarny2Aurélie Pagnon3Charlie K. Hee4Lauren Nakab5Dominique Sigaudo-Roussel6Bérengère Fromy7Laboratoire Biologie Tissulaire et Ingénierie ThérapeutiqueLaboratoire Biologie Tissulaire et Ingénierie ThérapeutiqueLaboratoire Biologie Tissulaire et Ingénierie ThérapeutiqueNOVOTECAllergan AestheticsAllergan AestheticsLaboratoire Biologie Tissulaire et Ingénierie ThérapeutiqueLaboratoire Biologie Tissulaire et Ingénierie ThérapeutiqueHyaluronic acid (HA), used in a variety of medical applications, is associated in rare instances to long-term adverse effects. Although the aetiology of these events is unknown, a number of hypotheses have been proposed, including low molecular weight of HA (LMW-HA) in the filler products. We hypothesized that cross-linked HA and its degradation products, in a low-grade inflammatory microenvironment, could impact immune responses that could affect cell behaviours in the dermis. Using two different cross-linking technologies VYC-15L and HYC-24L+, and their hyaluronidase-induced degradation products, we observed for nondegraded HA, VYC-15L and HYC-24L+, a moderate and transient increase in IL-1β, TNF-α in M1 macrophages under low-grade inflammatory conditions. Endothelial cells and fibroblasts were preconditioned using inflammatory medium produced by M1 macrophages. 24 h after LMW-HA fragments and HA stimulation, no cytokine was released in these preconditioned cells. To further characterize HA responses, we used a novel in vivo murine model exhibiting a systemic low-grade inflammatory phenotype. The intradermal injection of VYC-15L and its degradation products induced an inflammation and cell infiltration into the skin that was more pronounced than those by HYC-24L+. This acute cutaneous inflammation was likely due to mechanical effects due to filler injection and tissue integration rather than its biological effects on inflammation. VYC-15L and its degradation product potentiated microvascular response to acetylcholine in the presence of a low-grade inflammation. The different responses with 2D cell models and mouse model using the two tested cross-linking HA technologies showed the importance to use integrative complex model to better understand the effects of HA products according to inflammatory state.http://dx.doi.org/10.1155/2023/3001080
spellingShingle Benjamin Sanchez
Sandra Ferraro
Audrey Josset-Lamaugarny
Aurélie Pagnon
Charlie K. Hee
Lauren Nakab
Dominique Sigaudo-Roussel
Bérengère Fromy
Skin Cell and Tissue Responses to Cross-Linked Hyaluronic Acid in Low-Grade Inflammatory Conditions
International Journal of Inflammation
title Skin Cell and Tissue Responses to Cross-Linked Hyaluronic Acid in Low-Grade Inflammatory Conditions
title_full Skin Cell and Tissue Responses to Cross-Linked Hyaluronic Acid in Low-Grade Inflammatory Conditions
title_fullStr Skin Cell and Tissue Responses to Cross-Linked Hyaluronic Acid in Low-Grade Inflammatory Conditions
title_full_unstemmed Skin Cell and Tissue Responses to Cross-Linked Hyaluronic Acid in Low-Grade Inflammatory Conditions
title_short Skin Cell and Tissue Responses to Cross-Linked Hyaluronic Acid in Low-Grade Inflammatory Conditions
title_sort skin cell and tissue responses to cross linked hyaluronic acid in low grade inflammatory conditions
url http://dx.doi.org/10.1155/2023/3001080
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