Human dermal fibroblast response to hyaluronic acid-based injectable dermal fillers: an in vitro study

Abstract

Introduction: Hyaluronic acid (HA)-based injectable dermal fillers (IDFs) used in aesthetic procedures may increase fibroblast activity and ultimately improve subcutaneous tissue quality. Aim: To further our understanding of fibroblast response to different commercial HA-based IDFs. Material and methods: Normal human dermal fibroblasts (NHDFs) were cultured with four different commercially available HA-based IDFs to assess their effects on the synthesis of extracellular matrix components and regulators (type I collagen, type III collagen, elastin, and transforming growth factor (TGF)-β1) as well as pro-inflammatory and oxidative DNA damage markers (interleukin (IL)-1β and 8-hydroxy-2'-deoxyguanosine (8-OHdG)). The six biomarkers were measured in supernatants from NHDF cultures after 24 h, 48 h, and 72 h of exposure to HA-based IDFs. Results: All tested IDFs elicited a higher release of type I collagen in NHDF culture supernatants, although Juvederm Voluma was found to induce the most pronounced increase. Agex Fill Ultra induced the highest production of type III collagen and elastin. Levels of TGF-β1 and type I collagen in cell culture supernatants were positively correlated to each other (r = 0.57, p < 0.05). Conversely, 8-OHdG concentrations were inversely associated with both type III collagen (r = -0.41, p < 0.05) and elastin (r = -0.46, p < 0.05). Conclusions: Commercially available HA-based IDFs may elicit different in vitro fibroblast responses -a finding with potential implications in the prediction of their effects in aesthetic procedures. Our results also confirm that in vitro experiments may be viable tools for testing the effects of HA-based IDFs without resorting to animal studies.

Real-World Outcomes of Lip Augmentation Using a Hyaluronic Acid-Based Filler With Low 1,4-Butanediol Diglycidyl Ether Content: A Prospective, Open-Label, Multicenter, Post-marketing Study

“…The promising efficacy and safety outcomes observed in this study are likely due to the specific formulation properties of the product, specifically its low BDDE content. Prior in vitro experiments have demonstrated that HA-based fillers with reduced BDDE concentrations promote the production of type III collagen and elastin over type I collagen in human fibroblasts [ 13 ]. While type I collagen contributes to skin strength, type III collagen is associated with elasticity and suppleness [ 13 ].…”

“…Prior in vitro experiments have demonstrated that HA-based fillers with reduced BDDE concentrations promote the production of type III collagen and elastin over type I collagen in human fibroblasts [ 13 ]. While type I collagen contributes to skin strength, type III collagen is associated with elasticity and suppleness [ 13 ]. Agex Fill Volume®, by inducing the synthesis of type III collagen and elastin, has the potential to function as a peculiar ECM modulator, providing a more natural and supple appearance for lip augmentation.…”

“…Agex Fill Volume®, by inducing the synthesis of type III collagen and elastin, has the potential to function as a peculiar ECM modulator, providing a more natural and supple appearance for lip augmentation. Moreover, fillers with low BDDE content have been associated with lower levels of oxidative DNA damage in human fibroblasts, as indicated by 8-hydroxydeoxyguanosine measurements, compared to traditional HA-based fillers [ 13 ]. While this suggests that Agex Fill Volume® may offer long-term safety in lip enhancement procedures, further in vivo investigations and long-term prospective studies are necessary to validate and confirm this hypothesis.…”

“…The commercially available filler Agex Fill Volume® (Biodue SpA, Barberino Tavarnelle, Italy) is characterized by its low BDDE content, below 0.01 ppm, and its combination of cross-linked HA with a molecular weight of two million daltons and linear HA with a molecular weight of one million daltons. These physicochemical properties make it suitable for applications beyond traditional volume restoration, such as acting as a biological modulator of the extracellular matrix (ECM) [ 13 ]. While Agex Fill Volume® is indicated for facial contouring, its safety and efficacy for perioral rejuvenation and lip augmentation have not been thoroughly evaluated in clinical practice.…”

Clinically Actionable Topical Strategies for Addressing the Hallmarks of Skin Aging: A Primer for Aesthetic Medicine Practitioners

“…They may exert bio-stimulatory effects, increasing fibroblast activity and stimulating collagen synthesis [ 117 ], which ultimately affects the quality of subcutaneous tissue. Despite the lack of systematic studies investigating the effects of dermal fillers on the hallmarks of skin aging, it is important to note that the most common chemical cross-linker used in hyaluronic acid-based dermal fillers, 1,4-butanediol diglycidyl ether (BDDE), may potentially induce oxidative DNA damage in the form of 8OHdG [ 118 ]. The feasibility of incorporating a DNA repair enzyme like OGG1 to mitigate potential BDDE-induced genomic instability warrants further investigation.…”