Biomimetic agents and analogs for dental remineralization: A scoping review and functional classification

To map biomimetic agents for enamel and dentin remineralization, categorize them by composition and mechanism of action, and identify evidence levels to highlight research gaps.

This scoping review followed PRISMA guidelines, with the full methodology pre-registered on the Open Science Framework platform.

A comprehensive search of the PubMed/MEDLINE, Scopus, Embase, and Web of Science databases was performed in March 2024. Eligible studies that applied biomimetic materials or their analogs directly to human or animal enamel and/or dentin were included. Studies that incorporated biomimetic analogs into restorative materials were excluded.

Of the 1338 articles identified, 82 studies met the eligibility criteria for descriptive analysis. The evidence base was dominated by in vitro investigations (n = 73), with fewer in situ studies (n = 6), and randomized clinical trials (n = 2). Based on predominant mechanistic mode of action, biomimetic agents were classified into four categories: self-assembling templates (n = 34 studies), ion-binding directors (n = 28), biopolymer scaffolds (n = 15), and direct mineralizers (n = 5). All 82 studies reported remineralization-related outcomes. Enamel remineralization was investigated in 56 studies and dentin remineralization in 26 studies, with 3 studies evaluating both substrates. The most frequently reported outcomes included mechanical properties restoration (n = 34), lesion depth reduction and mineral gain (n = 32), transformation of amorphous calcium phosphate to crystalline hydroxyapatite (n = 24), and intrafibrillar/extrafibrillar dentin remineralization (n = 5).

This scoping review synthesizes a broad range of biomimetic agents for dental remineralization and organizes them into four mechanistic categories. It provides a structured framework to guide future research and clinical translation. However, the evidence base is largely derived from in vitro studies. This highlights the need for well-designed clinical trials to validate their therapeutic effectiveness in patients.