Odontogenesis by Endocytosis of Peptide Embedding Bioactive Glass Composite

Limited therapeutic options are available for treating deep caries. Those materials with potential of a dual effect to remineralize hard tissue and regenerate defective dentin tissues could be used as a new strategy for deep caries treatment. However, the application of the single component remains a challenge mainly because they lack calcium and phosphorus, are easily degraded, and are difficult to retain in the intricate body fluid environment. Considering the abundant source of calcium and phosphorus as well as the delivery performance of mesoporous bioactive glass (MBG), an amelogenin-derived peptide (QP5), which has a significant role in hard tissue remineralization, was loaded to fabricate a novel composite. After the synthesis of highly ordered MBG using a sol-gel method, the QP5 peptide was loaded increasingly by its extensive porous structure and enhanced electrostatic absorption. When used in an acidic environment, the MBG/QP5 composite presented pH-responsiveness, releasing therapeutic ions and functional peptides in a sequential cascade, and eventually adjusted the pH to a neutral state. The composite was internalized by dental pulp cells through a clathrin-mediated pathway and influenced by cell membrane lipid raft regulation. It could be also transported through the macro-pinocytotic pathway. Compared to the single treatment of peptide QP5 in 48 h, the composite facilitated a higher level of retention of the intracellular peptides. The composite further promoted migration and odontogenesis of dental pulp cells, including the improved activity of alkaline phosphatase, increased formation of mineralized nodules, and upregulated expression of mineralization-related genes compared to using MBG or QP5 alone. The composite further induced the dentin-like layer in a rat pulp capping model. The results suggested that this intelligent material with pH-responsiveness provides a promising alternative treatment method for biomimetic restoration of deep caries.