Immunomodulatory and cytotoxic effects of dental methacrylates: a narrative review focusing on 2-hydroxyethyl methacrylate and triethylene glycol dimethacrylate

Polymer resin-based dental materials may release unreacted monomers, including 2-hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA), which can interact with host tissues and influence biological responses. This narrative review summarizes current evidence on the immunomodulatory and cytotoxic effects of these commonly used dental methacrylates. A total of 42 in vitro and in vivo studies were included. The available evidence indicates that HEMA and TEGDMA can modulate immune responses, alter cytokine production, induce oxidative stress and DNA damage, and reduce cell viability, with TEGDMA generally appearing more cytotoxic than HEMA. Both monomers have been reported to increase pro-inflammatory cytokine release and to exhibit adjuvant-like effects in the presence of antigens. In contrast, co-exposure to bacterial components such as lipopolysaccharide and lipoteichoic acid was associated with attenuated microbe-induced cytokine responses, indicating a context-dependent immunomodulatory profile. Overall, the biological effects of HEMA and TEGDMA vary according to concentration, cell type, and experimental conditions, with both immunostimulatory and immunosuppressive effects reported. These findings highlight the complex biological activity of dental methacrylates and underscore the need for careful evaluation of their biocompatibility and clinical safety.