Comparative cytocompatibility of commercial theobromine‐ and fluoride‐containing topical varnish extracts in human gingival fibroblast‐1 cell

Abstract Theobromine has been proposed as a non‐fluoride remineralizing alternative; however, its cellular biocompatibility in oral cell models remains insufficiently characterized. This study compared the cytocompatibility of a theobromine‐containing varnish with two fluoride‐containing varnishes in human gingival fibroblast cell line (HGF‐1). HGF‐1 cells were exposed to extracts prepared from Group 1, Rennou Varnish; Group 2, MI Varnish; and Group 3, Clinpro Clear Fluoride Treatment at concentrations ranging from 0.0625% to 2%. Cell viability and cytotoxicity were evaluated using MTT and lactate dehydrogenase (LDH) assays after 24 h. Cell migration was assessed by wound‐healing assay using IC 50 /2 concentrations. Estimated IC 50 values were 0.611% for Group 1, 0.056% for Group 2, and 0.117% for Group 3, with corresponding 95% confidence intervals. Group 1 maintained higher viability and lower LDH release than the fluoride‐containing varnishes across most concentrations. Migration was comparable between Groups 1 and 2, whereas Group 3 caused the greatest reduction. These findings should be interpreted as preliminary formulation‐level in vitro responses of commercial varnish extracts and should not be attributed to the intrinsic cytocompatibility of any single active ingredient or excipient.