Figure 3.

Schematic overview of dentin properties in each phase of bone defect healing. (a) Inflammatory phase: Macroscopically, dentin particles (blue) are surrounded by a blood clot (pink) which is infiltrated by inflammatory cells, fibroblasts and MSCs. Microscopically, the dentin releases factors which attract neutrophils encouraging removal of debris and factors which promote differentiation of neutrophils and macrophages to the anti-inflammatory, wound healing N2 and M2 phenotypes. Dentin attracts MSCs and induces osteogenic differentiation initiating woven bone production. The dentin also releases angiogenic factors which encourage vessel growth into the grafted area. (b) Regenerative phase: Macroscopically woven bone (patterned orange) forms near the defect edges and the dentin particles to form mechanically robust bridges (black arrows) where bone ankyloses with the dentin. Microscopically, the dentin particle surface and tubules allow for intimate contact of osteoblasts with the graft particles. The osteoblasts accept the mineralized dentin as bone hydroxyapatite and form more mineralized tissue. Transmission of mechanical force stimulates mineralization. Non-inflammatory external replacement resorption via bone remodeling units is initiated. (c) Remodeling phase: The dentin particles are integrated into the bone structure which evolves to laminar bone (patterned orange). The similar mechanical strength of the dentin means it is well matched to the bone thus reducing stress fracturing. Remodeling of the bone results in a slow non-inflammatory resorption of the dentin particles while maintaining mechanical strength. Diagram is schematic to illustrate principles and not to scale.