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 Streptococcus mutans (S. mutans) without disrupting the oral normal flora. At a concentration of 8 μM mL−1, it exhibits the ability to prevent S. mutans' 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 S. mutans’ 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.

Keywords

• Targeted antimicrobial therapy
• Mineralization
• Caries
• Self-assembly hydrogel
• Transcriptomic analysis
• Molecular dynamics analysis