Design of Peptide-Guided Mineralization towards Self-Enamel Regeneration and Its Translation Challenges in Dentistry

Abstract

This review critically examines peptide-guided biomimetic mineralization as a platform for autonomous enamel regeneration, with emphasis on amelogenin-derived peptides (P26, QP5, and LRAP), self-assembling peptide systems such as P11-4, and nanomaterial-assisted delivery platforms. Peptide systems regulate hydroxyapatite nucleation, crystal growth, and localized ion delivery, enabling the formation of enamel-like mineral within demineralized lesions. Injectable peptide hydrogels and nanocomposite mineralizing matrices are also discussed based on published literature. The review also discusses the principal translational barriers that currently limit clinical implementation, including peptide instability in saliva, uncontrolled ion release, incomplete enamel crystal orientation, weak adhesion to demineralized enamel, insufficient long-term mechanical durability, and the limited availability of high-quality randomized clinical evidence. Overall, amelogenesis-inspired smart biomaterials represent a promising strategy for autonomous enamel regeneration, although significant advances in biomaterial design, crystal organization, and clinical validation are still required for commercial production and clinical practice.