Granulation phase

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 immobilized sufficiently, the granulation phase is disturbed.

What is the Granulation Phase?

Bones can regenerate completely after fractures. A broken bone is either a direct or an indirect fracture. In the case of direct bone fractures, the fracture points are in contact with each other or at least not more than a millimeter apart. Direct fracture healing is also known as primary fracture healing.

This is to be distinguished from secondary fracture healing. In indirect bone fractures, the fragments are more than a millimeter apart. During healing, the gap between the bone fragments is bridged by a callus, which is mineralized for stabilization.

Secondary fracture healing takes place in five phases. The third phase is the granulation phase. During this phase, granulation tissue forms in the fracture area, creating a soft callus. Meanwhile, osteoclasts remove bone tissue that is not supplied with blood. The resulting callus is mineralized with calcium during the callus hardening phase. The soft callus consists of reticular connective tissue. The granulation can be seen in the form of a hilly structure on all wounds and corresponds to granular braids in the cytoplasm.

Function & task

Immediately after a bone fracture, a hematoma forms at the fracture site. Immunological processes initiate an inflammatory response. The immune cells clean the breakpoint of bacteria and secrete substances that cause repair cells to break. During the inflammatory phase, there is increasing vascularization. The oxygen supply to the cells is improved and the vascularization attracts not only blood cells but also cells from the vascular endothelium. Fibroblasts are attracted by mediators and migrate into the fracture hematoma. There the fibroblasts form collagen, which organize the fracture hematoma step by step. This step initiates the granulation phase, also known as Soft callus phase referred to as.

Macrophages break down the fibrin threads in the hematoma and osteoclasts remove necrotic bone tissue. This is how the granulation tissue is created in the fracture area. This tissue mainly contains inflammatory cells, collagen fibers and fibroblasts and is then traversed by capillaries.

The angiogenesis increases and reaches about two weeks after the bone fracture six times the norm. Mineral deposits are already located between the collagen fibrils. In addition to increased vascularization, the granulation phase is accompanied by intensive proliferation and the immigration of cells from the mesenchyme.

These cells originally come from the endosteum and the periosteum. The mesenchymal cells become chondroblasts, fibroblasts or osteoblasts depending on the mechanical situation, the oxygen tension and the size of the fracture gap. If the vascular supply is reduced by compression, cartilage is formed in this way.

High oxygen tension with an intensive vascular supply leads to the formation of reticular connective tissue. Fibrous connective tissue and the fibrous cartilage are subsequently converted into fiber bones, so that a three-dimensional braided bone is created. On the surface, this mesh increases in thickness. This is how the stratum fibrosum stands out from the periosteum. The osteoblasts form this bone by means of ossification in the form of intramembranous ossification. Because the cartilage is not bound to actual blood vessels, it mainly arises in the areas directly adjacent to the fracture gap. A cartilage structure bridges the fracture gap in the late granulation phase until the callus tissue has hardened and the blood supply to the tissue is secured.

Type II collagen, which is provided by the chondrocytes, is primarily required for the granulation phase. The soft callus phase takes place within two to three weeks. The fracture is then connected by a cartilage, which is mineralized into a bone in the subsequent phase.

Illnesses & ailments

Ossification disorders can impair, delay or even make impossible the secondary fracture healing. Some ossification disorders are congenital and related to abnormal mesenchymal cells. Others are acquired and deal with circumstances such as poor diet. The secondary fracture healing and the granulation phase are disturbed, for example, in primary diseases such as osteoporosis or vitreous bone disease.

In addition to ossification disorders, poor blood circulation can also delay the granulation phase of secondary fracture healing. Reduced blood flow can be present in the context of various primary diseases. Circulatory disorders in the context of diabetes mellitus can cause more or less severe complications in fracture healing. Reduced activity of the immune system can also be a hindrance to the granulation phase. If there is insufficient immune activity, the fracture site will not be adequately cleared of bacteria. The inflammatory phase of the fracture healing then takes place insufficiently and the vascularization is disturbed as the basis of the granulation phase. In the worst case, an infection of the fracture site occurs due to decreased immune activity, which can spread through the blood system in the body and thus cause sepsis.

In the case of normal immune constitution, the granulation phase can also be interrupted or made more difficult by insufficient immobilization of the affected bone. In the worst case, the soft callus tears again when the affected bone is stressed and the healing of the fracture is delayed. One of the most common consequences of delayed fracture healing is pseudarthrosis, which is associated with swelling and functional impairment of the affected extremity.