Impaired wound healing in diabetic patients is associated with altered inflammatory responses, poor angiogenesis, deficient extracellular matrix (ECM) component, and peripheral neuropathy. To develop a wound dressing that is capable of the controlled delivery of bioactive small molecules that can improve diabetic wound healing, dimethyloxalylglycine (DMOG)-embedded poly(ε-caprolactone) (PCL) fiber (PCLF/DMOG) meshes are fabricated by electrospinning, and the effects of the PCLF/DMOG meshes on wound healing in diabetic rats are evaluated. Electrospun PCLF/DMOG meshes increase not only the wound closure, re-epithelialization ratio, epithelial maturation (K-10-positive epidermis), and collagen-positive area but also the numbers of angiogenic marker (CD-31)-positive and neuronal marker (neurofilament)-positive cells compared to PCLF (p < 0.05). In in vitro examinations, RAW264.7 macrophages grown on PCLF/DMOG meshes enhance the expression of growth factors (IGF-1, HB-EGF, and NGF) and anti-inflammatory factors (TGF-β1 and IL-4) but decrease that of pro-inflammatory factors (IL-1β and IL-6). Keratinocyte migration is increased by conditioned media from the cultures of the macrophages grown either in the presence of DMOG or on PCLF/DMOG. Collectively, these results indicate that PCLF/DMOG meshes promote impaired wound healing in diabetic rats by modulating macrophage responses, enhancing angiogenesis and nerve innervation, and improving ECM synthesis.
Keywords: angiogenesis; diabetes mellitus; dimethyloxalylglycine; electrospun fiber; nerve innervation; wound healing.