Diabetic Wound-Healing Science

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.

Determinants of the Fatigue Life of Musculoskeletal Tissues

While the effects of physical risk factors on MSD development have been a primary focus of musculoskeletal disorder (MSD) research, it is clear that psychological stressors and certain personal characteristics (e.g., aging, sex, and obesity) are also associated with increased MSD risk. The psychological and personal characteristics listed above share a common characteristic: all are associated with disruption of the body’s neuroendocrine and immune responses resulting in an impaired healing process. An impaired healing response may result in reduced fatigue life of musculoskeletal tissues due to a diminished ability to keep pace with accumulating damage (perhaps reparable under normal circumstances), and increased vulnerability of damaged tissue to further trauma owing to the prolonged healing process. Research in engineered self-healing materials suggests that decreased healing kinetics in the presence of mechanical loading can substantially reduce the fatigue life of materials. A model of factors influencing damage accrual and healing will be presented.

Therapeutic Potential of Luteolin on Impaired Wound Healing in Streptozotocin-Induced Rats

Long-term hyperglycemia may lead to diabetic microvascular and macrovascular complications that can affect the peripheral vascular system, particularly in wound healing capacity. Impaired angiogenesis and delayed wound healing are significant clinically. Luteolin (3′, 4′, 5, 7-tetrahydroxyflavone) is a naturally occurring flavonoid that is ubiquitously found in plants. Recent evidence has shown that luteolin is an anti-inflammatory and anti-oxidative agent. However, the effect of systemic luteolin administration on diabetic wound restoration remains unclear. Herein, we explored the effectiveness of luteolin for improving delayed and impaired healing of skin wound and further clarified the underlying mechanisms. The results indicated that luteolin significantly attenuates blood glucose concentration, improves impaired healing and accelerates re-epithelization of skin wound in streptozotocin (STZ)-induced diabetic rats. Histopathological staining and immunoblotting revealed an inhibitory effect of luteolin on inflammatory cell and cytokine production. We also observed remarkable decreases in protein expressions of inflammatory factors including matrix metalloproteinase (MMP)-9, tumor necrosis factor (TNF)-α, interleukin (IL-6), and IL1-β and downregulation of nuclear factor (NF)-κB, as well as increases in anti-oxidative enzymes such as superoxide dismutase 1 (SOD1) and glutathione peroxidase (GSH-Px) induced by nuclear factor erythroid 2-related factor (Nrf)-2 following luteolin supplementation. Furthermore, luteolin decreased the expression of vascular endothelial growth factor (VEGF) and increased the expression of ubiquitin carboxy-terminal hydrolase (UCH)-L1, as evidenced by angiogenesis and neuronal regeneration in completely healed wound. In conclusion, systemic administration of luteolin promotes wound restoration by ameliorating inflammation and oxidative stress through the inactivation of NF-κB and upregulation of Nrf2 in STZ-induced diabetic rats.

Wound healing complications with lenvatinib identified in a pharmacovigilance database

The U.S. Food and Drug Administration (FDA) has approved several vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors, including lenvatinib, for thyroid and renal malignancies. Inhibition of the VEGFR signaling pathway impairs angiogenesis and can disrupt wound healing. The objective of this work was to evaluate wound healing complications as a potential safety risk for patients treated with lenvatinib. We searched the FDA Adverse Event Reporting System (FAERS) database for postmarketing reports of wound healing complications with lenvatinib between 13 February 2015 (FDA approval date) and 15 February 2017. The search identified nine FAERS cases of lenvatinib-associated wound healing complications that were not previously reported in the medical literature. Seven cases involved postoperative wound healing complications, such as impaired healing or wound dehiscence. In our case series, the reported time to identification of delayed wound healing from tissue injury or surgery varied over a wide range (4–58 days). The time of initial lenvatinib exposure relative to the tissue injury was also highly varied in our series, which may have influenced the development and detection of impaired healing. FAERS case-level evidence suggests that lenvatinib may have contributed to wound healing complications based on temporality and biologic plausibility. Healthcare professionals should be aware of this safety risk to facilitate prompt recognition and risk mitigation.