Scaffolds have been reported to promote healing of burns and chronic wounds. Previous work showed that functionalizing scaffolds with antisense oligodeoxynucleotides (asODN), targeting the gap junction protein, Cx43, promoted wound healing and reduced inflammatory response. Sustained release of asODN was achieved but re-epithelisation failed to occur over the scaffolds. Here, we explored wet electrospinning to fabricate three-dimensional fibrous scaffolds, of two different materials, polycaprolactone (PCL) and PCL with 20% rat tail type 1 collagen (PCL/coll), that better mimic the extracellular matrix (ECM) of skin dermis while encapsulating asODN. Scaffolds were assessed on rat full-thickness wound re-epithelisation, inflammation, angiogenesis, and formation of new ECM within the scaffold during the first 5 days of healing. We found that PCL/coll impeded wound re-epithelisation and induced a bulbous thickening of wound edge epidermis as opposed to the thin tongue of migratory keratinocytes that was seen with PCL scaffolds. A significant inflammatory response was observed with PCL/coll but not with PCL. Interestingly, PCL increased the formation of new blood vessels within the scaffolds at day 3 post-injury, which enhanced the formation of new ECM within these scaffolds. This formation of new ECM within the scaffolds was key towards inducing the re-epithelization over the scaffolds as seen at day 5 post-injury. Wet electrospun PCL scaffolds encapsulating asODN could serve as a possible therapeutic approach for chronic wound ulcers by providing a sustained delivery of asODN and a biocompatible environment for cells to deposit new ECM for re-epithelisation over the implanted scaffolds.