Enhancing Collagen Mineralization with Amelogenin Peptide: Toward the Restoration of Dentin
Kaushik Mukherjee, Gayathri Visakan, Jin‐Ho Phark, Janet Moradian‐Oldak
Abstract
Mammalian teeth primarily consist of two distinct calcified tissues, enamel and dentin, that are intricately integrated by a complex and critical structure, the dentin-enamel junction (DEJ). Loss of enamel exposes the underlying dentin, increasing the risk of several irreversible dental diseases. This paper highlights the significance of utilizing the functional domains of a major enamel matrix protein, amelogenin, intrinsic to tooth enamel and the DEJ interface, to rationally design smaller bioinspired peptides for regeneration of tooth microstructures. Using this strategy, we designed a synthetic peptide, P26, that demonstrates a remarkable dual mineralization potential to restore incipient enamel decay and mineralization defects localized in peripheral dentin below the DEJ. As a proof of principle, we demonstrate that interaction between P26 and collagen prompts peptide self-assembly, followed by mineralization of collagen fibrils in vitro. P26-mediated nucleation of hydroxyapatite (HAP) crystals on demineralized dentin in situ significantly facilitates the recovery of mineral density and effectively restores the biomechanical properties of dentin to near-native levels, suggesting that P26-based therapy has promising applications for treating diverse mineralized tissue defects in the tooth.