The biology of fracture healing is a complex process involving specific regenerative patterns and changes in gene expression. It includes both intramembranous and endochondral bone formation. Indirect healing is the most common pathway, requiring minimal stability, while direct healing needs anatomical reduction and rigid fixation. The process begins with an acute inflammatory response, recruiting mesenchymal stem cells to form a cartilaginous callus, which later undergoes revascularization, calcification, and remodeling to restore normal bone structure. Key factors include TNF-α, IL-1, IL-6, and VEGF, which regulate inflammation, angiogenesis, and bone formation. Mesenchymal stem cells are crucial for bone regeneration, guided by SDF-1/CXCR-4 signaling. The callus is initially cartilaginous, then replaced by woven bone, and finally remodeled into lamellar bone. Bone remodeling is driven by osteoclasts and osteoblasts, requiring adequate blood supply and mechanical stability. Direct healing occurs without a callus, involving direct bone remodeling. Both contact and gap healing are forms of indirect healing, with gap healing requiring a smaller gap and longer remodeling. The process is influenced by various factors, including growth factors, metalloproteinases, and endocrine systems. Understanding these mechanisms is essential for developing therapies to improve fracture healing.The biology of fracture healing is a complex process involving specific regenerative patterns and changes in gene expression. It includes both intramembranous and endochondral bone formation. Indirect healing is the most common pathway, requiring minimal stability, while direct healing needs anatomical reduction and rigid fixation. The process begins with an acute inflammatory response, recruiting mesenchymal stem cells to form a cartilaginous callus, which later undergoes revascularization, calcification, and remodeling to restore normal bone structure. Key factors include TNF-α, IL-1, IL-6, and VEGF, which regulate inflammation, angiogenesis, and bone formation. Mesenchymal stem cells are crucial for bone regeneration, guided by SDF-1/CXCR-4 signaling. The callus is initially cartilaginous, then replaced by woven bone, and finally remodeled into lamellar bone. Bone remodeling is driven by osteoclasts and osteoblasts, requiring adequate blood supply and mechanical stability. Direct healing occurs without a callus, involving direct bone remodeling. Both contact and gap healing are forms of indirect healing, with gap healing requiring a smaller gap and longer remodeling. The process is influenced by various factors, including growth factors, metalloproteinases, and endocrine systems. Understanding these mechanisms is essential for developing therapies to improve fracture healing.