Fabrication, characterization, and in vivo implantation of eugenol-loaded nanogels and PCL/Cs electrospun nanofibers for wound healing applications

Developing wound dressings with a high potential to cover damaged skin tissue and facilitate cell adhesion and migration at the injury site is crucial in skin tissue engineering to accelerate wound healing. Electrospun nanofibers from natural/synthetic polymers are amongst the favorable wound dressings with appropriate physicochemical and biological properties. As well, nanoformulations of phenolic phytochemical “eugenol” have been shown to fasten wound healing via various anti-inflammatory and anti-oxidant effects. Herein, we developed a bi-component wound dressing of PCL/Cs electrospun nanofibers and eugenol nanogel to investigate its effects on tissue healing in vivo. PCL/Cs nanofibers were fabricated using an electrospinning method at the 15:1 ratio, and eugenol-loaded nanogels were synthesized by adding carboxymethylcellulose as the gelling agent, and their physicochemical characteristics were assessed. Scaffolds were implanted in a full-thickness excision wound model in Wistar rats, followed up for 21 days. The results showed that electrospun nanofibers had an average diameter of 228 nm with uniform and smooth morphology aligned randomly. Eugenol-loaded nanogel showed an average size distribution of 126 nm. Eugenol-loaded nanogel and nanogel + nanofiber groups significantly reduced wound surface area over 21 days. Histological evaluations showed that Eugenol-loaded nanogel and nanogel + nanofiber groups developed the full-thickness epidermis with the complete epithelium and stratum corneum, angiogenesis, and low macrophage infiltration in which predominantly mature collagen fibers were poorly and well organized, respectively. The combination of eugenol-loaded nanogel + PCL/Cs nanofiber accelerated wound healing by reducing inflammation, and edema along with enhancing angiogenesis, collagen synthesis, and re-epithelialization.