Enhanced reparative dentinogenesis of biphasic calcium phosphate ceramics containing calcium-deficient hydroxyapatite (CDHA) and strontium-incorporated CDHA in direct pulp capping

Abstract

Despite that dental materials and therapeutic strategies have made progress, reserving dental pulp vitality remains a great challenge during clinical practices of dentistry. Biphasic calcium phosphate (BCP) ceramic is a promising biomaterial for bone regeneration and dentin restoration, whose biological activities need to be further improved to meet the needs of regenerative medicine. Calcium-deficient hydroxyapatite (CDHA), which is more similar in composition to natural bone and tooth minerals, imparts superior bioactivity to BCP ceramics. Besides, owing to the positive roles of strontium in stimulating bone formation, the strontium-incorporated CDHA has excellent biocompatibility and further promotes bone regeneration. However, the effect of CDHA and strontium-incorporated CDHA in dental pulp capping has been rarely investigated. Herein, we presented an effective method to integrate CDHA and strontium-incorporated CDHA into BCP ceramics and investigated their biological properties as a potential strategy for dental pulp-capping and dentin regeneration. The characterization of phase composition and crystal structure confirmed that novel BCP ceramics with high CDHA content (BCP-A) and strontium-incorporated CDHA (BCP-A/Sr) have been successfully synthesized. In vitro, BCP-C (conventional BCP), BCP-A, and BCP-A/Sr provided an appropriate microenvironment and significantly promoted the proliferation of human dental pulp cells (hDPCs). BCP-A did not affect the migration of hDPCs, yet BCP-C and BCP-A/Sr displayed a suppressing trend. In vivo, BCP-A significantly reduced the inflammation response and improved the formation of reparative dentin bridges. Compared with mineral trioxide aggregate (MTA), a clinical direct pulp capping material, the texture of reparative dentin bridges in BCP-A showed more uniformity. Moreover, RNA-seq analysis further clarified that direct co-culture of hDPCs with BCP-A mainly up-regulated the cell cycle signaling pathway and CDC20 protein. These findings indicate that the novel BCP-A is a promising biomaterial for direct dental pulp capping due to its unique intrinsic biological activities, which warrants further investigation.