Effects of Dimethyloxalylglycine-Embedded Poly(ε-caprolactone) Fiber Meshes on Wound Healing in Diabetic Rats

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.