The high prevalence of early childhood caries, reaching 80-100% in some regions, highlights the need for safe, convenient products for long-term home remineralization therapy. Existing methods are limited by short enamel contact time, frequent dental visits, and risks associated with high fluoride concentrations in children. This study conducted a preclinical evaluation of the safety and efficacy of an innovative complex for remineralization therapy of initial caries in children. The complex consists of a self-forming thermoplastic mouthguard with time-dependent stiffness relaxation and a gel based on nano-hydroxyapatite and propolis. The study included an in vitro cytotoxicity assessment on HS-68 fibroblasts and remineralization potential on 40 demineralized primary teeth and an in vivo experiment on 30 Wistar rats evaluating acute and chronic toxicity, local irritant effects, and efficacy in a caries model induced by Streptococcus sobrinus. The complex components showed no cytotoxicity (cell viability 86–94%), no acute or chronic toxicity, and no local irritant effects. The gel increased enamel microhardness by 27.3% and raised the Ca/P ratio to 1.62, exceeding values of a standard fluoride gel (p < 0.05). In the rat caries model, the gel reduced lesion depth by 64.7% and decreased S. sobrinus counts by 2.6 log CFU/mL versus control (p < 0.01). The complex combines a high safety profile with proven remineralizing and antibacterial efficacy. The self-forming mouthguard with programmable stiffness relaxation ensures anatomical adaptation and safety for growing jaw tissues. These results support further clinical investigation for long-term home remineralization therapy of initial caries in preschool children.
