During the epithelialization phase of wound healing, mitosis takes place, closing the resulting tissue defect with new epithelial cells and initiating the subsequent phase of scar formation. The epithelization phase follows the granulation phase and hardens the granulation tissue formed up to that point. Excessive processes of epithelialization can cause wound healing disorders to occur with hyperkeratosis and hypergranulation.
What is the epithelialization phase?
The epithelialization phase, or reparative phase, of wound healing occurs approximately on the fifth to tenth day after tissue injury. The process of wound healing allows the human organism to compensate for various defects in the tissue. Small wounds require hardly any supportive measures to heal. In the case of bone, connective tissue and mucosa, the organism fully restores the tissue. In contrast, wound healing of all other tissues leaves scars. Overall, the wound healing process consists of five different phases. Hemostasis opens the process. This first phase is followed by the inflammation phase to cleanse the injured tissue. In the subsequent granulation phase, the first cells are formed to close the wound. The fourth phase is known as the reparative phase or epithelialization phase. The epithelialization phase serves to epithelialize the wound. The tissue defect is covered with epithelial cells during this phase and collagen matures into scar tissue. The epithelialization phase is followed by the final scar formation. The defect is securely closed after these processes.
Function and task
The epithelialization or reparative phase of wound healing occurs approximately on the fifth to tenth day after tissue injury. Immediately preceding this phase is the granulation phase. After the inflammatory cleansing of the wound, vessels and granulation tissue have formed in the area of the wound during this step. Fibroblasts, which were attracted by growth factors of the inflammatory phase, were predominantly involved in the formation of the connective tissue. By the epithelialization phase, the fibrin network produced during coagulation had been completely broken down by plasmin and thus underwent fibrinolysis. Meanwhile, the wound tissue is already firm due to the collagen produced and also contains proteoglycans. All these conditions are considered to start the epithelialization of the wound. A well granulated wound closes itself to one third by shrinking. The remaining two-thirds to wound closure occurs in the epithelialization phase by mitosis (cell division) of the epidermal cells. At the same time, fibrin undergoes cell migration from the wound edge to the wound center along the gliding path of the wound. The cell division processes taking place at the same time are regulated by chalones, i.e. statins within the epidermis and fibroblasts. Due to the injuries to the epidermis, only a few chalones are present. Since chalones have an inhibitory effect on mitotic processes, the cell division rate increases with injury. Once the wound is closed in the epithelialization phase, epidermal cells produce sufficient chalones to inhibit cell division processes. The first third of wound closure occurs in the epithelialization phase by wound contraction, which is performed by fibroblasts. During the phase, fibroblasts partially transform into fibrocytes and partially transform into myofibroblasts. Myofibroblasts contain contractile elements. For this reason, they can contract similar to a muscle cell and thus bring the wound edges closer together. Mitotic new epithelial cell formation occurs on the basis of the lower basal cell layer. This type of granulation tissue soon forms collagen fibers. The wound tissue becomes increasingly water– as well as vessel-poor. Elastic fibers are not formed at this stage. The wound therefore continues to consolidate. After about two weeks, the wound edges are firmly joined. The scar tissue is narrow and initially shows a light red color and soft consistency. With the epithelization phase and final scar formation, wound healing has come to an end.
Diseases and complaints
Medically, wound healing of larger skin wounds is supported via staples or sutures. These aids are removed only after the epithelialization phase is complete. After the epithelization phase has been completed, a further three months pass before the scar is fully resilient.However, if the wound area is overloaded in the three subsequent months, the young tissue will tear again in extreme cases. The cell division processes of the epithelization phase must then be repeated. A lack of inhibition of the cell division processes after completion of the epithelialization phase can cause tumors, hyperkeratoses and hypergranulation. Hyperkeratoses are keratinizations of the squamous epithelium. Orthokeratotic are distinguished from parakeratotic hyperkeratosis. The former phenomenon is a thickening of the stratum corneum during regular keratinocyte differentiation processes. In parakeratotic hyperkeratosis, on the other hand, the stratum corneum thickens during disturbed differentiation processes of the keratinocytes. In connection with uninhibited cell division in and possibly after the epithelialization phase, proliferative hyperkeratoses occur most frequently, which are based on accelerated cell growth within the epithal stratum basale. This profiling results in increased cell turnover with thickening of the stratum corneum. More and more keratinocytes are formed, which become corneocytes. Hypergranulation must be distinguished from hyperkeratosis. This is an excessive formation of granulation tissue during the epithelialization phase of wound healing. Hypergranulation occurs as a wound healing complication primarily in chronic wounds and is due to slow or insufficient epithelialization. The connection between tumors and processes of the epithelialization phase has in turn been reflected in a common saying among medical professionals. Tumors are wounds that do not heal, according to pathologist Dr. Harold Dvorak. In fact, this statement has now been confirmed at the molecular level. Parallels have been discovered between wound healing epithelialization and cancer, such as the similarity between the gene expression pattern of healing wounds and the gene expression patterns of malignant tumors.
