User:BryceH2331/Bone healing

Secondary healing
== Secondary healing (also known as indirect fracture healing) is the most common form of bone healing. It usually consists of only endochondral ossification. Sometimes, intramembranous ossification occurs together with endochondral ossification. Intramembranous ossification, mediated by the periosteal layer of bone, occurs with the formation of callus. For endochondral ossification, deposition of bone only occurs after the mineralized cartilage. This process of healing occurs when the fracture is treated conservatively using orthopaedic cast or immobilization, external fixation, or internal fixation. ==

Reaction
== After a bone 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 include; 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 the blood capillary permeability. Inflammation peaks by 24 hours and is completed in seven days. Through tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 2, TNFα mediates the differentiation of mesenchymal stem cells (originated from the bone marrow) into osteoblast and chondrocytes. Stromal cell-derived factor 1 (SDF-1) and CXCR4 mediate the recruitment of mesenchymal stem cells. IL-1 and IL-6 are the most important cytokines for bone healing. IL-1 promotes the formation of the callus and blood vessels. IL-6 promotes the differentiation of osteoblasts and osteoclasts. All cells within the blood clot degenerate and die. Within this area, the fibroblasts replicate. Within 5-11 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. ==