The granulation phase is the third phase of secondary fracture healing and is characterized by the formation of a soft callus to bridge the fracture. The soft callus is mineralized with calcium during the callus hardening phase. If the affected bone is not adequately immobilized, the granulation phase is impaired.
What is the granulation phase?
Secondary fracture healing proceeds in five phases. The third phase is the granulation phase. Bones can regenerate completely after fractures. A bone fracture is either a direct or indirect fracture. In direct fractures, the fracture sites are in contact with each other or at least no more than a millimeter apart. Direct fracture healing is also called primary fracture healing. Secondary fracture healing must be distinguished from this. In indirect fractures, the fracture fragments are more than one millimeter apart. During healing, the gap between the fracture pieces is bridged by a callus, which is mineralized for stabilization. Secondary fracture healing proceeds in five phases. The third phase is the granulation phase. In this phase, granulation tissue forms in the fracture zone, creating a soft callus. Meanwhile, osteoclasts remove bone tissue that has not been perfused. The resulting callus is mineralized with calcium in the callus hardening phase. The soft callus consists of reticular connective tissue. Granulation is evident in the form of a mound structure on all wounds and corresponds to granule-like meshwork in the cytoplasm.
Function and purpose
Immediately after a bone fracture, a hematoma forms at the fracture site. Immunologic processes initiate an inflammatory response. Immune cells clear the fracture site of bacteria and secrete substances that lead repair cells to the fracture. During the inflammatory phase, vascularization increases. The oxygen supply to the cells thus improves and vascularization attracts cells from the vascular endothelium in addition to blood cells. Fibroblasts are attracted by mediators and migrate into the fracture hematoma. There, fibroblasts form collagen, which organizes the fracture hematoma step by step. This step initiates the granulation phase, also known as the soft callus phase. Macrophages degrade the fibrin filaments in the hematoma and osteoclasts remove necrotic bone tissue. Thus, the granulation tissue is formed in the fracture area. This tissue contains mainly inflammatory cells, collagen fibers, and fibroblasts, and is further permeated by capillaries. Angiogenesis increases and reaches six times the normal level about two weeks after the fracture. Mineral deposits are already present between the collagen fibrils. In addition to increased vascularization, the granulation phase is accompanied by intense proliferation and immigration of cells from the mesenchyme. These cells originate from the endost and periosteum. The mesenchymal cells become chondroblasts, fibroblasts or osteoblasts depending on the mechanical situation, the oxygen tension and the size of the fracture gap. In the case of a low vascular supply due to compression, cartilage is formed in this way. High oxygen tension with intensive vascular supply leads to the formation of reticular connective tissue. Fibrous connective tissue and the fibrocartilage are subsequently remodeled into fibrous bone, resulting in a three-dimensional meshwork bone. On the surface, this meshwork increases in thickness. Thus, the stratum fibrosum stands out from the periosteum. Osteoblasts form this bone by means of ossification in the form of intramembranous ossification. Because cartilage has little attachment to actual blood vessels, it forms primarily in areas directly adjacent to the fracture gap. Thus, a cartilage structure bridges the fracture gap in the late granulation phase until callus tissue hardening has occurred and blood supply to the tissue is assured. The granulation phase mainly requires type II collagen, which is provided by the chondrocytes. The soft callus phase takes place within two to three weeks. The fracture is then connected by cartilage, which is mineralized into bone in the subsequent phase.
Diseases and complaints
Ossification disorders can impair, delay, or even prevent secondary fracture healing.Some ossification disorders are congenital and related to abnormal mesenchymal cells. Others are acquired and related to circumstances such as improper nutrition. Secondary fracture healing and the granulation phase are thus disturbed in primary diseases such as osteoporosis or brittle bone disease. In addition to ossification disorders, poor perfusion can also delay the granulation phase of secondary fracture healing. Decreased blood flow may be present in the setting of various primary diseases. Circulatory disturbances in the context of diabetes mellitus can thus cause more or less severe complications during fracture healing. Reduced activity of the immune system can also be an obstacle to the granulation phase. If there is insufficient immune activity, the fracture site is not sufficiently cleared of bacteria. The inflammatory phase of fracture healing then takes place inadequately and vascularization is disturbed as the basis of the granulation phase. In the worst case, due to reduced immune activity, infection of the fracture site occurs, which can spread throughout the body via the blood system, causing sepsis. In addition, with a normal immune constitution, the granulation phase may be interrupted or complicated by inadequate immobilization of the affected bone. In the worst case, the soft callus ruptures again due to loading of the affected bone, and fracture healing is delayed. One of the most common consequences of delayed fracture healing is pseudarthrosis, which is associated with swelling and functional limitations of the affected limb.
