Table 4.

The key events and the signaling molecules involved in the bone repair and regeneration process [18,88,94,95].

Bone Repair Phase	Key Events	Signaling Molecules
Inflammation	Production of pro-inflammatory cytokines, chemokines, and growth factors Recruitment of polymorphonuclear neutrophils, macrophages, and platelets Activation of the blood coagulation cascade Formation of hematoma Angiogenesis	Tumor necrosis factor-α Interleukin-1, -6, -11, -18 Platelet-derived growth factor Transforming growth factor-b1 Tumor-derived growth factor-β Insulin-like growth factor Fibroblast growth factor-2
Bone production	Differentiation of progenitor cells into chondrocytes Formation of fibrocartilage Fibrocartilage calcification Woven bone deposition	Bone morphogenetic protein Tumor-derived growth factor-β2 and -β3
Bone remodeling	Differentiation of osteoprogenitor cells into osteoblasts and osteoclasts Resorption of woven bone Deposition of lamellar bone	Interleukin-1, -6, -11, and -12 Tumor necrosis factor-α Interferon-γ