Two-stepped pH-responsive peptide microsphere/carboxymethyl chitosan complex: enhanced protection of an inflamed dentin–pulp complex

Dental caries is the most prevalent infectious disease affecting oral health, leading to the destruction of tooth hard tissues and dental pulp inflammation. The dentin-pulp complex, as the biological core of the tooth, can generate reparative dentin to protect the dental pulp from infection progression. However, untreated carious lesions chronically disrupt the structural integrity and reparative capacity of the dentin-pulp complex, thereby significantly compromising pulp vitality as deep caries progresses. In this study, a two-stepped pH-responsive peptide microsphere/carboxymethyl chitosan complex (PM/CS) was designed to offer comprehensive protection for the inflamed dentin-pulp complex. PM/CS has a three-dimensional network structure, and it constructs an intelligent drug delivery system by integrating TVH-19 self-assembled peptide microspheres that we developed earlier into carboxymethyl chitosan. This complex not only exhibited pH-controlled release characteristics, but also showed antibacterial properties against <i>Streptococcus mutans</i> and a mineralization-promoting effect on human dental pulp cells (hDPCs). PM/CS exerted acute anti-inflammatory effects on early pulpal lesions in rats, while longitudinal studies revealed its remarkable capacity to induce tertiary dentinogenesis, indicating therapeutic efficacy through biological modulation. This study provides a potential pulp capping complex material for the restoration treatment of the dentin-pulp complex under the influence of deep caries.