Fig. 2
Bone regeneration is a complex and interconnected process that occurs in distinct phases. In the first phase (week 1), hematoma formation occurs, where the coagulation cascade triggers both pro-inflammatory and anti-inflammatory events, coordinated by IL-1, IL-6, TNF-α, VEGF, and RANKL, involving M1 and M2 macrophages, Th1 and Th2 cells, and fibroblasts. During week 2 to 3 soft callus formation and angiogenesis occur, involving endothelial cells, hypertrophic chondrocytes, and osteoblasts. During week 4−17 complex callus formation is characterized by matrix mineralization and woven bone development, with the participation of endothelial cells, osteocytes, osteoblasts, and osteoclasts. The bone remodeling phase (week 18–52) involves remodeling using TGF-β and MMPs, which affects endothelial cells, osteocytes, osteoblasts, and osteoclasts, thereby improving the healed fracture and restoring the functional bone structure. This complex temporal and cellular orchestration is the foundation for the successful regeneration of bone tissue. The figure here is based on the work of S. Park and Y. Niu et al. VEGF vascular endothelial growth factor, RANKL nuclear factor κB ligand, MMP matrix metalloproteinases.227,228 Copyright © 2024 Elsevier Ltd
