Amelogenin-Inspired Autoadaptive Peptide in a Caries Microenvironment Facilitates Long-Term Protection of the Dentin–Pulp Complex

Dental caries, one of the most prevalent infectious diseases, is the primary contributor to the early loss of natural teeth and is a significant public health issue. Known as the tooth's bioactive core, the dentin-pulp complex (DPCX) comprises tightly connected hard and soft tissues that not only serve as a biological barrier for the inner tooth tissue but also produce reparative dentin following mild disruptions. While efforts to preserve DPCX are numerous, most strategies focus on temporary antibacterial measures, inflammation reduction, or tissue regeneration, lacking a comprehensive, long-lasting solution. In this study, TVH-19, an autoadaptive peptide mimicking the pH- and ion-responsive capacity of amelogenin, was designed to exert multifaceted preservation of DPCX, providing a comprehensive strategy for preserving vital pulp. Leveraging its unique amphiphilicity-related cell penetration and ion/pH-responsive self-assembly properties, TVH-19 outperforms conventional pulp preservation materials by being capable of rapid cell penetration, minimizing diffused side effects, providing environment-responsive self-assembly/disassembly for balanced long-term antibacterial and cell protection, and facilitating the formation of lysosomal-escaping intracellular aggregates for the continuous activation of PDGFRα⁺ dental pulp stem cells.