Abstract
Background: Crosslinked hyaluronic acid (HA)-based hydrogels are commonly used as dermal fillers where they interact with surrounding tissues including host stromal and immune cells. HA fillers are widely used for aesthetic applications, with products designed with varying properties depending on their indication. Although HA fillers have been demonstrated to have a strong biocompatibility profile, a small subset of patients' experiences delayed-onset adverse events hypothesized to be inflammatory and allergy-related outcomes such as delayed-onset hypersensitivity. Aims: The overall goal of this study was to evaluate the innate and adaptive immune response to two clinically available HA filler formulations. Methods: Using multiparametric flow cytometry, we characterized the immune response to Juvèderm Volbella (VYC-15 L) and Juvèderm Ultra 3 (SGD-30XP) in a murine quadricep muscle resection that enables implantation of larger volumes and exposure to muscle and adipose. Results: Presence of the implanted HA filler increased recruitment of immune cells, specifically antigen presenting macrophages, eosinophils, and gamma-delta (γδ) T cells to the injury site compared to no implant (saline) controls. Comparing the two materials, VYC-15 L increased interleukin 17a (IL17a) production by lymphocyte subsets at the injury site and induced higher levels of circulating IgE relative to SGD-30XP and saline controls. Conclusion: Overall, these results provide insights into the immune response to HA fillers and how different formulations may alter the immune outcomes.