<Ul> <Li> v. Remodeling to original bone contour </Li> </Ul> <Li> v. Remodeling to original bone contour </Li> <P> After fracture, blood cells accumulate adjacent to the injury site . Soon after fracture, blood vessels constrict, stopping further bleeding . Within a few hours, the extravascular blood cells form a clot called a hematoma that acts as a template for callus formation . These cells, including macrophages, release inflammatory mediators such as cytokines (tumor necrosis factor alpha (TNFα), interleukin - 1 family (IL - 1), interleukin 6 (IL - 6), 11 (IL - 11), and 18 (IL - 18)) and increase blood capillary permeability . Inflammation peaks by 24 hours and completes by seven days . Through tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 2, TNFα mediates the differentiation of mesenchymal stem cell (originated from the bone marrow) into osteoblast and chondrocytes . Stromal cell - derived factor 1 (SDF - 1) and CXCR4 mediate recruitment of mesenchymal stem cells . IL - 1 and IL - 6 are the most important cytokines for bone healing . IL - 1 promotes formation of callus and of blood vessels . IL - 6 promotes differentiation of osteoblasts and osteoclasts . All cells within the blood clot degenerate and die . Within this area, the fibroblasts replicate . Within 7 - 14 days, they form a loose aggregate of cells, interspersed with small blood vessels, known as granulation tissue . Osteoclasts move in to reabsorb dead bone ends, and other necrotic tissue is removed . </P> <P> Seven to nine days after fracture, the cells of the periosteum replicate and transform . The periosteal cells proximal to (on the near side of) the fracture gap develop into chondroblasts, which form hyaline cartilage . The periosteal cells distal to (at the far end of) the fracture gap develop into osteoblasts, which form woven bone through bone resorption of calcified cartilage and recruitment of bone cells and osteoclasts . The fibroblasts within the granulation tissue develop into chondroblasts which also form hyaline cartilage . These two new tissues grow in size until they unite with each other . These processes culminate in a new mass of heterogeneous tissue known as a fracture callus . Callus formation peaks at day 14 of fracture . Eventually, the fracture gap is bridged . </P>

When does the healing process of a fractured bone begin
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