Wound Definition and Treatment Principles

Wound, which is defined as the deterioration of tissue integrity due to physical, chemical, thermal, radiation, spontaneous or surgical reasons, is an event that is closely related to all surgeons and has to be treated by health personnel frequently. With injury begins a complex sequence of events for tissue repair. In reality, wound healing is a mechanism with both cellular and extracellular components. The effects and functions of cells that play a role in wound healing are regulated by many growth factors and cytokines that function in the area of injury in vivo.
Ideal wound healing can be defined as the recovery of the normal anatomical, physiological and histological structure of the tissue that has lost its integrity. However, wound healing is not a linear event in which growth factors trigger cell migration and proliferation. On the contrary, it is a dynamic and interactive event in which soluble factors, shaped blood elements, extracellular matrix and parenchymal cells participate.

There are 4 distinct sequential phases that cannot be clearly separated from each other in wound healing. The first event that occurs after tissue injury is the initiation of coagulation and vasoconstriction, both intrinsically and extrinsically, as a result of injury to blood vessels and extravasation of red blood cells and other blood cells.

Inflammation occurs as the second step of the response to tissue damage and is initiated by histamine, kinins, and prostaglandin products. However, in the early stages of this phase, the dominant cell of the injury site is neutrophils. In addition to phagocytosis, neutrophils also secrete proinflammatory cytokines that activate local fibroblasts and keratinocytes. In a few days, while the dominance of neutrophils disappears, monocytes pass from the capillaries to the extravascular space by diapedesis. Collagen fragments, fibronectin, elastin and transforming growth factor – β ( TGF – β ) are held responsible for the chemotaxis and migration of monocytes. Macrophages, one of the most important cells in wound healing, are the primary source of cytokines that initiate fibroblast proliferation, collagen synthesis and other healing processes. These include tumor necrosis factor – α ( TNF – α ), platellet derived growth factor ( PDGF ), transforming growth factor – α ( TGF – α ), Insulin like growth factor ( IL – GF ) and fibroblast growth factor ( FGF ).

Mesenchymal cells have an important role in wound healing in the following periods. In the early period after injury, the wound matrix is composed of fibrin, clots and small amounts of substances such as fibronectin and vitronectin. However, later, fibroblasts in the surrounding healthy tissues migrate into the matrix with the effect of chemotactic cytokines. There are many chemotactic cytokines for fibroblasts. However, TGF-α and PDGF provide proliferation and differentiation of these cells as well as fibroblast chemotaxis.
Angiogenesis provides the repair of vascular structures of tissues damaged by injury. Endothelial cell proliferation, which develops with budding, mostly occurs with cytokines released from macrophages.

Repair of the epidermal layer is necessary to rebuild the barrier between the internal and external environment that has been disrupted by injury. For this purpose, epithelialization takes place on the wound matrix. The cellular activity that occurs during this event can be listed as cellular separation, migration, proliferation and epidermal cell differentiation. Thickening of the basal cell layer at the wound margin is the first stage of reepithelialization. The marginal basal cells then elongate, detach from the underlying basement membrane, and migrate towards the wound, providing epithelialization. While epithelial cell migration and proliferation are stimulated by TGF-α and epidermal growth factor (EGF), TGF-β only provides cell migration.

In the late period of wound healing, collagen synthesis and destruction work together and reshape, while contraction occurs in the wound. The presence of foreign bodies or bacteria from the injury site at the end of the inflammation period may turn the normal wound healing scenario into chronic inflammation. Similarly, failure of the cells in the injury area to respond appropriately to the stimuli conveyed by cytokines for any reason, or the disruption of these functions of the cells that perform autocrine or paracrine stimulation may prevent the complete realization of wound healing, resulting in chronic wound formation.

CHRONIC WOUNDS

Bed sores, diabetic wounds and venous ulcers are the most important examples of chronic wounds. These types of wounds exhibit a very poor wound healing profile despite intensive surgical and medical treatment. It is known that for normal wound healing, migration and proliferation of fibroblasts, endothelial cells and epithelial cells, together with fibroplasia, angiogenesis and reepithelialization must occur. Wound contraction, which occurs by a mechanism different from smooth muscle cells, is an important component of healing. Although the mechanism of wound contraction provided by fibroblasts has not been fully elucidated, it is thought to originate from specialized fibroblasts – myofibroblasts. However, it seems like a rational approach to argue that the most important task in wound healing is performed by keratinocytes, which act as a modulator for the cells involved in wound healing.
Patients with chronic wound problems are usually elderly and in negative catabolic state; The main problems in wound healing in these patients can be summarized as delayed wound contraction, decreased neovascularization, slowed epithelialization, and proliferation and dysfunction in cells that contribute to wound healing.

An increase is observed in the number of patients admitted to hospitals due to chronic wounds as a result of the prolongation of their life span with the development of medical and surgical treatment approaches. USA. Considering that approximately 5 million people were hospitalized and treated for chronic wounds in a study conducted in Turkey, it can be estimated how much financial loss this caused. Hospitalization of patients puts a great burden on hospitals. In another study conducted in Sweden, it was determined that foot wounds are a health problem that concerns 0.2 – 0.3% of the population. Although there is no healthy statistical study in our country, considering that we have worse health conditions than the countries in question, it can be argued that a serious number of people are facing this type of problem. Beyond the complications that cause delayed wound healing, wounds that develop due to events such as corticosteroid use, radiotherapy, chemotherapy and malnutrition are also included in this group. Despite all this, no effective treatment method has been developed for chronic wounds or delayed wound healing until now.

The most important cause of bedsores is the degeneration of the subdermal and perforator vessels and circulatory disorders in the tissues caused by pressure on the bony prominences. But bedsores are a pathology that occurs only in humans. Although the clinical significance of this problem is clear, the biochemical mechanism of pathological events in the healing of bedsores is not fully understood. Pressure ulcers have been reported to occur in approximately 3 to 4% of hospitalized patients. In the treatment, it is recommended to eliminate the pressure on certain areas, to take measures that increase tissue perfusion, and to eliminate risk factors such as the treatment of the primary disease. In the surgical treatment of bedsores, wound debridement, appropriate dressing and surgical closure of the wound are recommended. However, it has been reported that the use of cultured keratinocytes to accelerate the wound healing of the wound gives satisfactory results. The reasons for wound healing in venous ulcers have been partially revealed, but improvements in treatment are far from satisfying clinicians. The lower extremity is a very problematic area in terms of wound healing. Although the wounds that occur here are usually of venous origin, arterial disorders, causes due to hematological diseases and infectious pathogens should also be considered. The main pathology in venous ulcers caused by subfascial and epifascial venous insufficiency is deep vein thrombosis. Lymphatic insufficiency, microthrombi, pericapillary fibrosis and microedema and leukocyte dysfunction are blamed in its physiopathology. However, the net result in the clinic is a non-healing wound in the lower extremity. Compressive bandage, increasing venous tone and edema prophylaxis are recommended for treatment. However, in the surgical treatment of such wounds, fasciotomy, vein dissection and bypass interventions are in question, apart from methods for direct wound closure such as skin grafting. There is no study in the literature on interactive wound dressing with cultured keratinocyte. Similarly, in arterial wounds, besides the attempts to correct the actual pathology, the most important approach is to close the wound with skin grafts. However, in this type of wounds, the treatment of the wound with the method suggested in our study-interactive dressing- is not yet included in the literature.

The most important and common example of chronic wound is diabetic wounds. Wound complications are encountered in approximately 25% of diabetic patients and 10-15% of them require surgical treatment. Diabetic foot prolongs hospitalization at a higher rate than other diabetes-related complications. Chronic and delayed healing dermal ulcers are one of the most important problems of diabetic patients. Delayed wound healing, inadequate granulation tissue formation, and lack of epithelialization and wound contraction appear to be due to cellular dysfunction in fibroblasts and keratinocytes. Oxidative stress is considered to be one of the most important pathogenic factors in diabetic wound complications and is thought to inhibit cell survival and replication. Depending on the source, diabetic wounds can be classified as atherosclerotic, peripheral neuropathy and microangiopathy. In diabetic atherosclerosis, the lesion characteristically presents as a necrotic lesion due to local ischemia located on the sole and heel or on the lateral aspect of the foot. Polyneuropathy in diabetes leads to sensory and motor losses and results in paresis and paralysis. With the loss of the pain stimulus, position changes and pressure sores may occur, and the disorder in the innervation of the small vessels contributes to local ischemia. Microangiopathy develops as a result of vessel wall damage caused by high glucose level in endothelial cells. All wounds that develop in diabetic patients are highly prone to infection because the immune response in patients is already impaired. In the treatment of this type of wounds, apart from controlling high glycemia, mechanical wound care and debridement are recommended when necessary, but there is no publication in the literature on the cultured keratinocyte and interactive wound dressing prescribed in our study.

On the other hand, it is vital to replace the skin as soon as possible after traumas such as burns, in which the human epidermis separates the internal environment of the body from the external environment, creates a physical barrier against microorganisms and maintains the heat balance. In extensive burns, this is not usually possible and the patient has to use different methods to close the wounds. These include allogeneic or xenogenic skin grafts, homografts and synthetic skin equivalents. However, in recent years, the closure of burn wounds with cultured keratinocyte grafts obtained in the laboratory is observed as a method that saves the lives of patients. In addition, dermis equivalents obtained in the laboratory environment have an important place in wound closure. It provides temporary closure with a silicone layer on the human dermis, which has been used in recent years, and this layer is replaced with cultured keratinocytes, resulting in permanent wound closure.

The skin application to the culture in the closure of burn wounds is provided by a real graft holding. The cultured skin graft applied here is a graft consisting of an average of 4-6 layers obtained in tissue culture laboratories. The most important reason here can be summarized as the lack of sufficient blood flow in the bed for graft attachment and the fact that the cells in this area do not actively participate in wound healing. Therefore, it can be summarized as producing small signals used in the treatment of chronic wounds and transmitting them to other cells involved in wound healing. It would not be wrong to argue that the cultured keratinocytes used in this sense are an initiator and promoter of wound healing.

Many agents such as many growth factors and antioxidants have been applied exogenously in both normal and pathological wound healing and have been reported to have a positive effect on wound healing in the experimental field. Although these studies show that growth factor treatment approaches have clinical importance, the value of local use is still controversial. Therefore, in the treatment of chronic wounds, the treatment of the primary stress causing the event is of great importance in order for the cells to respond correctly to the signals. However, it seems that the most important mechanism of this approach is to ensure that the cells that play a role in wound healing of the cultured keratinocytes applied to the wound with the method prescribed in our study, respond to the signals in an accurate and timely manner.