Irisin-Loaded Cerium-Containing Mesoporous Bioactive Glass for Effective Immunomodulation and Odontogenesis of Dental Pulp Cells.

Recently, vital pulp therapy (VPT) has emerged as a promising strategy for dental pulp treatment because of the preservation of the pulp tissue. The efficacy of VPT relies on the use of VPT agents; however, commonly used VPT agents, including calcium hydroxide (CH), possess several limitations, such as dental pulp cells (DPCs) stimulation. In this study, we report the design of a novel VPT agent by loading Irisin onto cerium-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) to generate Irisin/Ce-MBGNs. Compared to CH, which do not exhibit any obvious anti-inflammatory effect, Irisin/Ce-MBGNs have been shown to enhance the function of mitochondria in macrophages, regulate the M2 polarization, significantly reduce the intracellular ROS level, and alleviate the expression of pro-inflammatory factors. Furthermore, the Irisin/Ce-MBGNs nanocomposite effectively preserved DPCs stemness and promoted the odontogenic differentiation of human DPCs. Results in in vivo experiments showed that Irisin/Ce-MBGNs could form thicker reparative dentin surrounding the perforation holes than CH. The superior treating efficacy of Irisin/Ce-MBGNs is attributed to the synergistic effects of both Irisin and cerium components for the effective immunomodulation and odontogenesis of DPCs. Hopefully, this work contributes to the design of more advanced VPT agents for future implementation in clinical use.