Body processes

Granulation Phase – Function, Task & Diseases

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 in the callus hardening phase . If the affected bone is not sufficiently immobilized, the granulation phase is disturbed.

What is the granulation phase?

Bones can fully regenerate after fractures. A broken bone is either a direct or indirect fracture. In the case of direct bone fractures, the fracture points are in contact with one another or at least are no more than a millimeter apart. Direct fracture healing is also referred to as primary fracture healing.

This is to be distinguished from secondary fracture healing. In the case of 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 to stabilize it.

The secondary fracture healing proceeds in five phases. The third phase is the granulation phase. In this phase, granulation tissue forms in the fracture area, resulting in soft callus. Osteoclasts , meanwhile, 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 . Granulation is evident in the form of a hillock structure on all wounds and corresponds to granular meshwork 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 rupture site of bacteria and secrete substances that cause repair cells to rupture. In the inflammatory phase , there is increasing vascularization . This improves the oxygen supply to the cells 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 the soft callus phase .

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

Angiogenesis increases and reaches six times the norm around two weeks after the bone fracture. There are already mineral depots between the collagen fibrils. In addition to increased vascularization, the granulation phase is accompanied by intensive proliferation and the migration of cells from the mesenchyme .

These cells originally come from the endosteum and the periosteum. Depending on the mechanical situation, the oxygen tension and the size of the fracture gap, the mesenchymal cells become chondroblasts, fibroblasts or osteoblasts . In the event of reduced vascular supply due to compression, cartilage forms in this way .

High oxygen tension with intensive vascular supply leads to the formation of reticular connective tissue. Fibrous connective tissue and fibrocartilage are subsequently converted into fibrous bone, resulting in three-dimensional woven bone. On the surface, this network 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 has little contact with actual blood vesselsis bound, it arises primarily in the areas directly adjacent to the fracture gap. In the late granulation phase, a cartilage structure bridges the fracture gap 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 occurs within two to three weeks. The fracture is then connected by cartilage, which is then mineralized into bone.

Diseases & Ailments

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 poor diet . The secondary fracture healing and the granulation phase are disturbed , for example, in primary diseases such as osteoporosis or brittle 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 serious complications during fracture healing. Reduced activity of the immune system can also hinder the granulation phase. With insufficient immune activity, the fracture site does not get enough of bacteriacleaned. The inflammatory phase of the fracture healing then takes place only insufficiently and the vascularization is disturbed as the basis of the granulation phase. At worst, reduced immune activity can result in infection at the fracture site, which can spread through the body’s blood system, causing sepsis .

With a 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 due to stress on 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 in the affected extremity.

Lisa Newlon
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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.