Synergistic remineralisation of enamel adjacent to orthodontic brackets using self-assembling peptide with calcium phosphate and fluoride systems: An in vitro study

Objective: To compare the remineralisation potential of self-assembling peptide P11-4 (SAP), casein phosphopeptide–amorphous calcium phosphate (CPP-ACP), fluoride-enriched CPP-ACP (CPP-ACFP) and their combinations under a dynamic pH-cycling model simulating conditions adjacent to orthodontic brackets. Methods: This in vitro study included 104 sound human premolars that were demineralised and randomly allocated to eight groups (n = 13): control, SAP, fluoride varnish (F), CPP-ACP, CPP-ACFP, SAP + F, SAP + CPP-ACP and SAP + CPP-ACFP. Specimens underwent 28 demineralisation–remineralisation cycles over 30 days. Quantitative light-induced fluorescence assessed fluorescence loss (ΔF, %) and integrated fluorescence loss (ΔQ, mm² × %) at four intervals (T 1 –T 4 ). Intra- and inter-group differences were analysed using Friedman, Wilcoxon, Kruskal–Wallis and Bonferroni-adjusted Mann–Whitney tests (α = 0.05). Results: All experimental groups showed significant time-dependent remineralisation ( P < 0.001). SAP + CPP-ACFP showed the greatest cumulative improvement (ΔF ΔT = +6.27; ΔQ ΔT = +4.4), followed by SAP + CPP-ACP and SAP + F. Among the individual agents, CPP-ACFP showed greater improvement than CPP-ACP, fluoride varnish and SAP. Combination regimens produced 20%—30% greater improvement than the individual agents. Conclusions: All regimens produced measurable remineralisation, with SAP + CPP-ACFP showing the most favourable response. The findings support the complementary action of peptide-guided crystal nucleation and fluoride-stabilised calcium–phosphate replenishment and suggest a promising minimally invasive approach for managing orthodontically induced white-spot lesions.