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

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)-b1) as well as pro-inflammatory and oxidative DNA damage markers (interleukin (IL)-1b 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-b1 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.