Diabetic Wound-Healing Science

Abstract

Diabetes mellitus is an increasingly prevalent chronic metabolic disease characterized by prolonged hyperglycemia that leads to long-term health consequences. It is estimated that impaired healing of diabetic wounds affects approximately 25% of all patients with diabetes mellitus, often resulting in lower limb amputation, with subsequent high economic and psychosocial costs. The hyperglycemic environment promotes the formation of biofilms and makes diabetic wounds difficult to treat. In this review, we present updates regarding recent advances in our understanding of the pathophysiology of diabetic wounds focusing on impaired angiogenesis, neuropathy, sub-optimal chronic inflammatory response, barrier disruption, and subsequent polymicrobial infection, followed by current and future treatment strategies designed to tackle the various pathologies associated with diabetic wounds. Given the alarming increase in the prevalence of diabetes, and subsequently diabetic wounds, it is imperative that future treatment strategies target multiple causes of impaired healing in diabetic wounds.

Effects of the Chinese Herb Medicine Formula “She-Xiang-Yu-Hong” Ointment on Wound Healing Promotion in Diabetic Mice

“…Loss of VEGF may be one of the main reasons for reduced neovascularization and delayed wound healing in diabetic patients. Platelet colorectal cancer cell adhesion molecule-31 (CD31) is expressed in close connection of skin endothelial cells, which is involved in angiogenesis [ 25 ]. Therefore, CD31 can also indicate the level of angiogenesis.…”

Perfil de pacientes com lesões cutâneas hospitalizados em uma unidade de internação de clínica médica

“…O pé diabético se apresenta como uma das mais comuns complicações dos pacientes com diabetes mellitus (DM), que associado a um processo de cicatrização prejudicado por essa comorbidade, se torna porta de entrada para desenvolvimento de infecções 6 . Estudos indicam que entre um e três, a cada cinco pacientes com DM, irão desenvolver feridas de difícil cicatrização, como um pé diabético 7 .…”

“…Em pacientes com DM, a hiperglicemia prejudica o fechamento das lesões cutâneas por conta dos processos de inflamação e infecção, elevado estresse oxidativo, neuropatia e complicações microvasculares, além do desenvolvimento de aterosclerose. Essas condições dificultam a circulação normal, impedindo a chegada de nutrientes necessários para a recuperação, em adição com a disfunção de células endoteliais aumentado pela HAS, obstando o processo de cicatrização dessas feridas 7 .…”

Decellularized Tissues for Wound Healing: Towards Closing the Gap Between Scaffold Design and Effective Extracellular Matrix Remodeling

“…Chronic wounds develop when normal wound healing is delayed or disrupted by different underlying pathological mechanisms, such as continuous inflammation, persistent infections, and necrosis (Raziyeva et al, 2021). Besides, chronic wounds are associated with the impairment of the following processes: growth factor production, angiogenic response, macrophage differentiation, collagen production, epidermal barrier function, granulation tissue formation, keratinocyte and fibroblast migration/proliferation, and bone healing (osteomyelitis has been reported as a predictor of inadequate wound healing and amputation (Burgess et al, 2021)). Compared with normal wound healing, chronic wounds are characterized by changes in the healing phases, as follows: 1) during hemostasis, the hypercoagulability and the decrease in fibrinolysis are altered (Erem et al, 2005); 2) during the inflammatory stage, there is an imbalance of inflammatory cytokines such as interleukin (IL)-1 (IL1), IL6, tumor necrosis factor-alpha (TNF-α), and interferon gamma (IFN-γ), as well as several growth factors, such as platelet derived growth factor (PDGF), epidermal growth factor (EGF), and insulin-like growth factor 1 (IGF-1) (Pradhan et al, 2009); 3) fibroblast and keratinocyte migration and proliferation are diminished; and 4) an imbalance between the accumulation of ECM components and their remodeling by MMPs (Brem and Tomic-Canic, 2007) (Figure 2).…”