ABSTRACT
Cutaneous wound healing is characterized by an intricate interplay of cell-signaling, migration, differentiation, and proliferation. Hemostasis, including the subsequent secretion of cytokines and chemotactic factors, is the fi rst of four stages of wound healing (Pradhan et al. 2010). The second stage involves the signifi cant role of an immune response via the infi ltration of monocytes, neutrophils, and leukocytes. Phagocytic cells clear debris, and perpetuate infl ammatory mechanisms. Healing is further characterized by rapid proliferation of cells involved in the repair and restoration of the damaged region. Among others: epithelia, endothelia, keratinocytes and fi broblasts migrate, differentiate, divide, and interact to replace the extracellular matrix (ECM) and injured tissue. Deposition of the ECM further promotes angiogenesis, migration, re-epithelialization, and wound closure. The fi nal remodeling stage is characterized by ECM modifi cation and scar tissue formation (Pradhan et al. 2009). The typical human internal environment is conducive to this appropriate response and resolution of disturbances. However, the hyperglycemic environment in diabetic individuals prevents the appropriate execution of the aforementioned
stages, thus contributing to persistent ulceration. Several studies have noted the pathogenesis of impaired ECM formation; abnormal cellular proliferation, migration, and infi ltration; insuffi cient macrophage activity; and impaired re-epithelialization and angiogenesis (Duraisamy et al. 2001; Khanna et al. 2010; Loots et al. 1998). In such instances pro-infl ammatory cytokines such as TNFα (Tumor Necrosis Factor α), IL-6 (Interleukin-6), and IL-8 (Interleukin-8, also known as CXCL8), as well as MCP-1 (Monocyte Chemo-attractant Protein-1) and MMPs (Matrix Metalloproteinases) are over-expressed (Landis et al. 2010). Wound persistence, perpetuated by chronic infl ammation and inappropriate immune responses in the hyperglycemic environment, leads to increased infection susceptibility. Therefore, treatment of diabetic wounds must involve attenuation of uncontrolled infl ammation by promoting appropriate cytokine expression and self-limitation, as well as, eliminating infection and the promotion of appropriate re-epithelialization and wound repair mechanisms.
