Non-healing foot ulcers in diabetic patients: general and local interfering conditions and management options with advanced wound dressings

Abstract

Medical knowledge about wound management has improved as recent studies have investigated the healing process and its biochemical background. Despite this, foot ulcers remain an important clinical problem, often resulting in costly, prolonged treatment. A non-healing ulcer is also a strong risk factor for major amputation. Many factors can interfere with wound healing, including the patient's general health status (i.e., nutritional condition indicated by albumin levels) or drugs such as steroids that can interfere with normal healing. Diabetic complications (i.e., renal insufficiency) may delay healing and account for higher amputation rates observed in diabetic patients under dialysis treatment. Wound environment (e.g., presence of neuropathy, ischaemia, and infection) may significantly influence healing by interfering with the physiological healing cascade and adding local release of factors that may worsen the wound. The timely and well-orchestrated release of factors regulating the healing process, observed in acute wounds, is impaired in non-healing wounds that are blocked in a chronic inflammatory phase without progressing to healing. This chronic phase is characterised by elevated protease activity (EPA) of metalloproteinases (MMPs) and serine proteases (e.g., human neutrophil elastase) that interfere with collagen synthesis, as well as growth factor release and action. EPA (mainly MMP 9, MMP-8 and elastase) and inflammatory factors present in the wound bed (such as IL-1, IL-6, and TNFa) account for the catabolic state of non-healing ulcers. The availability of wound dressings that modulate EPA has added new therapeutic options for treating non-healing ulcers. The literature confirms advantages obtained by reducing protease activity in the wound bed, with better outcomes achieved by using these dressings compared with traditional ones. New technologies also allow a physician to know the status of the wound bed environment, particularly EPA, in a clinical setting. These may be helpful in guiding a clinician's options in treating very difficult-to-heal ulcers.

Biology and Biomarkers for Wound Healing

“…Upon injury, hemostasis results in the formation of a fibrin clot whose constituents serve both as a scaffold and a source of growth factors and chemokines that recruit a gambit of cells, including inflammatory cells, to migrate into the wound bed 8–10 . Changes in the expression of numerous adhesion molecules on endothelial cells allow for the recruitment and extravasation of neutrophils and macrophages from the circulation to clear potential infection.…”

Smart Dressings Based on Nanostructured Fibers Containing Natural Origin Antimicrobial, Anti-Inflammatory, and Regenerative Compounds

“…Different factors may hinder those events including age, obesity, social causes, drugs or previous diseases [7,9,11,16,17,23]. Hypertrophic scars, which are the result of an excessive deposition of collagen, and non-healing (chronic) wounds are commonly present in the clinic [19].…”

“…[16,18,19]. Bacterial components have been highlighted as harmful factors during wound healing due to their interference with cell-matrix interactions and due a reduced inflammatory response they produce [16,23,29,30]. As in other infective processes, bacteria can colonize wounds as a biofilm which is a complex aggregate of bacteria embedded in an ECM with the ability to form a highly resistant impervious microenvironment against antibiotics while maintaining the inflammatory stage [31,32].…”

Harnessing electronic healthcare data for wound care research: Wound registry analytic guidelines for less‐biased analyses

“…Lack of mobility in general increases the risk that the wound will not heal, and is also a major factor for PUs in terms of prevention and treatment 60 Prior amputations in patients with DFUs put them at higher risk for amputations and failure to heal the wound 72-74 Initial wound area Wound area at first assessment (cm 2 ); preferably after any debridement Initial wound area is the most commonly used baseline parameters for endpoints Initial wound age Wound age at first assessment (days); should be based on most likely onset time for wound Older wounds have substantially lower chances of healing compared to younger wounds 60,67,75 Initial wound severity For DFUs: Wagner or UT grade; for PUs, stage The severity of the wound has a major impact on whether the wound will heal, healing time, and risk for amputation 67,74,76 ESRD: end stage renal disease; PVD: peripheral vascular disease. study conducted by Brown et al shows that the majority of guidelines have a high risk of bias, and the rest have an unclear risk of bias.…”