Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_896_Библиотеки_им_академика_М_И_Перельмана

CSS Clinical signs and symptoms DFUs Diabetic foot ulcers DNA Deoxyribonucleic acid ECM Extracellular matrix EGF Epithelial growth factor EPCs Bone marrow-derived endothelial progenitor cells

phenotype MDT Maggot debridement therapy MMP-9 Metalloproteinase-9 MSC Mesenchymal stem cells PDGF-ββ Platelet-derived growth factor-ββ rhEGF Human recombinant epidermal growth factor TGF-β Transforming growth factor-β TIME Tissue (Necrotic), Infection/Inammation,

However, this carefully coordinated cascade of events is dis­rupted in diabetic wound healing. The resulting consequence is a vicious cycle of impaired wound healing; therefore, this sequence is not applicable to these chronic wounds [14]. It has been well documented that diabetic ulcers and other types of chronic wounds do not follow an orderly and reli­able progression of wound healing [15, 16]. Diabetic ulcer­ations remain in a chronic pro-inammatory state that is characterized by increased expression of inammatory cytokines [17].

The healing process in diabetes is mainly characterized by the state of chronic inammatory conditions, disrupted angiogenesis, reduction of endothelial progenitor cells, and an imbalance in extracellular matrix regulation. As observed in wound repair, neutrophils and macrophages promptly inltrate the area of the lesion driven by chemotactic chemo­kines that are particularly elevated in diabetes [18]. Inltrating cells release inammatory cytokines such as interleukin 1β (IL-1β) and tumor necrosis factor α (TNFα) whose levels are not only elevated not only during the initial inammatory acute repair phase but remain at high concen­trations in the wound area for longer time. This indicates the maintenance of a prolonged inammatory response [19]. In diabetes, the production of several growth factors involved in initiating and sustaining the healing process is compromised. For instance, reduced levels of insulin-like growth factor-1 (IGF-1) and transforming growth factor-β (TGF-β) have been reported in the wound tissue in both diabetic animals and humans. IGF-1 is implied in cell granulation and wound reepithelization [20], while TGF-β recruits immune cells, keratinocytes, broblasts, and vascular cells and is involved in angiogenesis and formation of the ECM [21]. Transforming growth factor-β (TGF-β) is a key factor throughout the wound healing process. However, cells in chronic wounds may not appropriately respond to TGF-β [22]. In diabetes, the balance between the promotion of new vessel formation and their maturation is disturbed. Angiogenesis is dysfunc­tional in endothelial cells exposed to elevated glucose levels, and in the wound area, capillary density is poor and insuf­cient. Hyperglycemia affects hypoxia-inducible factor 1-alpha (HIF-1α) stability and activation, and consequently it suppresses HIF-1α target genes such as vascular endothe­lial growth factor (VEGF) [23]. In diabetes animal models, macrophages, which are the main source of VEGF, exhibit impaired phagocytic activity and altered phenotype, result­ing in failure of tissue repair [24]. Accordingly, in a mice wound model, VEGF-A mRNA and protein levels were sig­nicantly reduced compared to control mice. Treatment with VEGF-A caused accelerated wound closure, although this was characterized by early leaky and malformed vasculature

Schultz et al. rst published the concept of wound bed preparation in 2003, which is a structured framework for use in the management of wounds. The TIME acronym (Tissue, Inammation/infection, Moisture balance, Epithelial edge advancement), published the following year, describes four aspects of wound bed preparation that need to be systemati­cally addressed in order for wound healing to take place. This acronym has since been widely accepted in clinical practice in both the assessment and management of chronic wounds.

Debridement is an important part of WBP.However, debride­ment alone is not enough to sustain healing in chronic wounds/ulcers. In accordance with the TIME (necrotic Tissue, Infection/Inammation, Moisture balance, healing of Edge of wound) principles, debridement can help remove necrotic burden of abnormal or senescent cells and brous tissue (eschar), control inammation or infection, decrease excess moisture, and stimulate a non-advancing wound edge [58, 59]. By removing nonviable tissue, appropriate debride­ment of diabetic ulcers serves to correct several cellular (altered resident cells) and molecular (matrix material, growth factors, MMPs, and enzymes) abnormalities [60]. One hypothesis is that debridement resets the course toward restoring normal wound healing sequence [61] (Fig.21.2).

In the early stages of wound healing, debridement occurs autolytically through the action of neutrophil-derived enzymes. Protease inhibitors are also released by wound cells to restrict protease’s action to the wound bed and mini­mize damage to intact tissue at the wound edges. Although

Pressure off-loading is very important to remove a source of repetitive pressure and constant trauma and is essential in diabetic wound healing. Although there are many types of pressure-relieving devices, the total contact cast is consid­ered by many to be the best method for off-loading and treat­ing diabetic patients with neuropathic ulcers [79]. However, other options for off-loading have been developed and are utilized.