Caries is the most common disease in the world. Great efforts have been undertaken for prevention and to identify a regenerative treatment solution for dental caries. Self-assembling β-sheet forming peptides have previously shown to form 3-dimensional fiber networks supporting tissue regeneration. In particular, the self-assembling peptide P-4 has shown potential in the treatment and prevention of dental caries. It has previously been shown that application of monomeric P-4 solution to early carious lesions can increase net mineral gain by forming de novo hydroxyapatite crystals. The hypothesis for the mode of action was that monomeric self-assembling peptide P-4 diffuses into the subsurface lesion body and assembles therein into higher order fibrils, facilitating mineralization of the subsurface volume by mimicking the natural biomineralization of the tooth enamel, and it remains within the lesion body as a scaffold built-in by the newly formed hydroxyapatite. The aim of the present study was to investigate the mechanism of action of the self-assembling peptide P-4 supporting mineralization of carious enamel. By various analytical methods, it could be shown that the self-assembling peptide P-4 diffuses into the subsurface lesion, assembles into higher formed aggregates throughout the whole volume of the lesion, and supports nucleation of de novo hydroxyapatite nanocrystals and consequently results in increased mineral density within the subsurface carious lesion. The results showed that the application of self-assembling peptide P-4 can facilitate the subsurface regeneration of the enamel lesion by supporting de novo mineralization in a similar mode of action as has been shown for the natural formation of dental enamel.
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