Remineralization of Initial Carious Lesions Using Peptides: A Comprehensive Review

Initial carious lesions represent a reversible stage of the caries process in which non-operative strategies can prevent lesion progression and preserve dental hard tissues. This comprehensive review provides an overview of peptide-based approaches for the management of initial carious lesions, with emphasis on self-assembling peptides. The literature was identified through PubMed electronic searches complemented by manual screening of reference lists. Only randomized clinical trials and controlled clinical studies published in English were included. The PICOS framework guided the structure of the review, focusing on patients of any age with initial carious lesions, peptide-based interventions aimed at enamel remineralization, comparisons with placebo, alternative treatments, or standard preventive care (e.g., fluoride products), and outcomes related to de-/remineralisation. Overall, the available evidence suggests that peptide-based strategies can mimic natural biomineralization and promote subsurface hydroxyapatite formation. Among the investigated approaches, the self-assembling peptide P11-4 is the most extensively studied. Evidence supports its safety and its potential to enhance initial carious lesion remineralisation, with possible advantages over fluoride alone in selected cases. In conclusion, peptide-based potentially regenerative approaches, particularly P11-4, represent a promising adjunct in minimally invasive caries management, although further long-term and comparative clinical studies are needed to define their role in routine dental practice.