Wnt3a‐Loaded Hydroxyapatite Nanowire@Mesoporous Silica Core−Shell Nanocomposite Promotes the Regeneration of Dentin−Pulp Complex via Angiogenesis, Oxidative Stress Resistance, and Odontogenic Induction of Stem Cells

Abstract Pulp exposure often leads to pulp necrosis, root fractures, and ultimate tooth loss. The repair of the exposure site with pulp capping treatment is of great significance to preserving pulp vitality, but its efficacy is impaired by the low bioactivity of capping materials and cell injuries from the local accumulation of oxidative stress. This study develops a Wnt3a‐loaded hydroxyapatite nanowire@mesoporous silica (Wnt3a‐HANW@MpSi) core−shell nanocomposite for pulp capping treatments. The ultralong and highly flexible hydroxyapatite nanowires provide the framework for the composites, and the mesoporous silica shell endows the composite with the capacity of efficiently loading/releasing Wnt3a and Si ions. Under in vitro investigation, Wnt3a‐HANW@MpSi not only promotes the oxidative stress resistance of dental pulp stem cells (DPSCs), enhances their migration and odontogenic differentiation, but also exhibits superior properties of angiogenesis in vitro. Revealed by the transcriptome analysis, the underlying mechanisms of odontogenic enhancement by Wnt3a‐HANW@MpSi are closely related to multiple biological processes and signaling pathways toward pulp/dentin regeneration. Furthermore, an animal model of subcutaneous transplantation demonstrates the significant reinforcement of the formation of dentin–pulp complex‐like tissues and blood vessels by Wnt3a‐HANW@MpSi in vivo. These results indicate the promising potential of Wnt3a‐HANW@MpSi in treatments of dental pulp exposure.