Clinical applications of self-assembling peptides in dentistry: Enamel remineralization, dentin repair, and tissue regeneration

Dental caries is a dynamic process driven by an imbalance between demineralization and remineralization, traditionally managed by invasive restorative methods that sacrifice healthy tooth structure. The shift toward minimally invasive and regenerative dentistry has promoted interest in biomimetic materials, particularly self-assembling peptides (SAPs). P11-4 and RADA16 are among the most widely investigated peptides, capable of undergoing pH-triggered self-assembly into β-sheet nanofibers that form a three-dimensional hydrogel scaffold. This matrix acts as a template for hydroxyapatite nucleation, promoting guided enamel remineralization. Evidence demonstrates that P11-4 effectively regenerates early enamel lesions, including post-orthodontic white-spot lesions, with superior remineralization efficacy compared to fluoride and without compromising bracket bond strength. SAP-mediated biomineralization also shows potential in managing dentinal hypersensitivity through intratubular crystal deposition, as well as emerging applications in bone regeneration and pulp revascularization, supported by favorable biocompatibility and scaffold characteristics. However, challenges persist regarding stability, standardization of peptide design, and sensitivity of self-assembly to environmental conditions. This narrative review summarizes the mechanisms, applications, and limitations of SAPs in dentistry.