Targeted antimicrobial self-assembly peptide hydrogel with in situ bio-mimic remineralization for caries management.

Abstract

The single-function agents with wide-spectrum activity which tend to disturb the ecological balance of oral cavity cannot satisfy dental treatment need. A multi-functional agent with specifically targeted killing property and in situ remineralization is warranted for caries management. A novel multi-functional agent (8DSS-C8-P-113) consisting of three domains, i.e., a non-specific antimicrobial peptide (AMP) (P-113), a competence stimulating peptide (C8), and an enhancing remineralization domain (8DSS), is fabricated and evaluated in this study. The findings demonstrates that 2 μM mL^-1 of 8DSS-C8-P-113 eliminates planktonic <i>Streptococcus mutans</i> (<i>S. mutans</i>) without disrupting the oral normal flora. At a concentration of 8 μM mL^-1, it exhibits the ability to prevent <i>S. mut</i>ans' adhesion. Furthermore, 8DSS-C8-P-113 self-assembles a hydrogel state at the higher concentration of 16 μM mL^-1. This hydrogel self-adheres on the tooth surface, resisting acid attack, eradicating <i>S. mutans'</i> biofilm, and inducing mineralization in order to facilitate the repair of demineralized dental hard tissue. Its significant effectiveness in reducing the severity of dental caries is also demonstrated in vivo in a rat model. This study suggests that the multi-functional bioactive AMP 8DSS-C8-P-113 is a promising agent to specifically target pathogen, prevent tooth demineralization, and effectively induce in situ bio-mimic remineralization for the management of dental caries.