**1. Introduction**

Venous leg ulcer (VLU) represent a pathological tissue change in the form of a defect in the lower leg which occurs as a complication of chronic venous insufficiency (CVI) [1]. Chronic ulceration is defined as ulceration on the lower leg that lasts (does not heal) within 6 weeks, and is caused by various etiopathogenetic factors [2].

Venous leg ulcers often heal slowly and result in long-term suffering and intensive use of health care resources [3, 4]. A VLUs represent a growing health problem, and they are a condition that is very expensive to treat for both the health system and patients.

A VLUs endangers the patient's normal life. Treatment of VLUs requires dedication and cooperation between the patient and the doctor. The health-related impact of VLUs is increasingly recognized as a valuable outcome measure for assessing interventions, especially when complete cure is unlikely [5]. Adults with VLUs often have multiple disabling symptoms, including pain, sleep disturbance, depression, swelling of the lower extremities, fatigue and symptoms associated with inflammation of lower leg (redness, localized heat, discomfort due to high exudate levels and itching) [6].

The prevalence of VLU varies between 1.5–3% in the total population and 4–5% in persons over the age of 80 [1]. Studies have shown that 1–2% of the adult population either has or has had venous ulceration [7]. The prevalence of VLU in Western European countries in the population over the age of 18 is 0.1–0.3% [1].

It is very important to point out that a certain number of VLUs heal very slowly or not at all. In a period of about 4 months with the application of adequate therapy, about 50% of VLUs heals [8, 9]. However, about 20% of VLUs do not heal even after 2 years from the beginning of treatment, and about 8% even after 5 years from the beginning of treatment [1]. At the annual level, the recurrence rate of VLUs ranges from 6–15% [1]. The risk of recurrence over a period of 1 year ranged from 30–57% [1].

Risk factors for VLUs are numerous, and most patients have more than one. Most of these factors are immutable and this group includes being female, elderly, having previous venous thrombosis of the legs, pulmonary embolism, multiparity, musculoskeletal and joint diseases [7, 10]. Obesity and sedentarianism are risk factors that can be influenced on [11]. The genetic traits of an individual can also be emphasized as a predisposing factor [7, 12], but the specific gene or set of genes responsible for the occurrence of this disease has not been determined so far. In people with varicose veins, Forkhead box C2, located on chromosome 16q24 [13], was isolated.

Despite the application of different standard treatment modalities for VLUs, a certain percentage of venous ulcers do not heal. Studies have shown that prolonged healing time or refractoriness to applied therapy may be due to an increase of T lymphocytes and granulocytes, lack of oxygen, growth factor and cytokine imbalance [10]. For this reason, we are working on the development of modern therapeutic modalities, while the number of new techniques for the VLUs care has increased in recent years and is constantly improving [14].
