Badziukh S. Surgical treatment of patients with diabetic foot syndrome using cellular technologies

The thesis presents the solution of a relevant challenge which will improve the treatment efficacy of patients with chronic diabetic wounds using autologous plasminogen (Pg) in comprehensive surgical treatment. The study includes the data of examination and treatment of 45 patients, aged from 48 to 81 years, with chronic wounds associated with neuropathic diabetic foot syndrome, with wound defects ranging from 3 to 30 cm² in size. The sample formed two groups – a main group and a control group. The main group included 20 patients who, in addition to the standard treatment scheme for diabetic wounds, were locally administered autologous Pg on the affected area for 20 days. The control group included 25 patients with chronic diabetic wounds, who underwent the standard accepted scheme of surgical treatment with wound dressings, antiseptics, and ointment dressings. The effect of autologous plasminogen (Pg) was studied and analyzed by the changes in cytokine activity and proangiogenic factors in tissue samples of chronic wounds in patients of the main and control group. The criteria for clinical success of surgical treatment were considered as: the presence of an inflammatory reaction in tissues and the cleansing of the wound surface, reduction in pain, the appearance of granulation tissue and retraction of the wound area, the terms for complete closure of the wound surface, the number of surgical interventions, and the occurrence of infectious-inflammatory complications. In the first stage of the study, the angiogenesis factors and the activity of proteases in diabetic wounds were emphasized, with the comparison of these indicators in acute diabetic wounds. The author established that the expression of the central regulator of hypoxia-associated processes, hypoxia-inducible factor 1alpha (HIF-1α), in diabetic wounds increased by 4.4 times compared to the values in acute wounds. Meanwhile, western blot analysis of the vascular endothelial growth factor (VEGF) from samples of healthy and ulcerative tissues showed trace amounts of this growth factor in diabetic wounds. These characteristics indicated a sharply pronounced hypoxia in the wound tissues. At the same time, the expression of regulators counteracting angiogenesis and VEGF shifts the angiogenic balance towards ischemia. The total content of angiostatin in diabetic chronic wounds exceeded that in acute wounds by 2.5 times. These results mean that the angiogenic response, through the increased regulation of angiostatin formation, leads to a decrease in the tissue VEGF expression. The study compares the activity of matrix metalloproteinases (MMPs) in individuals with acute (surgical) wounds and trophic feet ulcers in patients with diabetes. Gelatin zymography showed that acute wounds contain trace amounts of the active isoform of MMP-9, whereas an increase in MMP-9 activity characterized diabetic ulcers.