Enhancing Diabetic Wound Healing Through Improved Angiogenesis: The Role of Emulsion‐Based Core‐Shell Micro/Nanofibrous Scaffold with Sustained CuO Nanoparticle Delivery

Abstract Attempts are made to design a system for sustaining the delivery of copper ions into diabetic wounds and induce angiogenesis with minimal dose‐dependent cytotoxicity. Here, a dual drug‐delivery micro/nanofibrous core‐shell system is engineered using polycaprolactone/sodium sulfated alginate‐polyvinyl alcohol (PCL/SSA‐PVA), as core/shell parts, by emulsion electrospinning technique to optimize sustained delivery of copper oxide nanoparticles (CuO NP). Herein, different concentrations of CuO NP (0.2, 0.4, 0.8, and 1.6%w/w) are loaded into the core part of the core‐shell system. The morphological, biomechanical, and biocompatibility properties of the scaffolds are fully determined in vitro and in vivo. The 0.8%w/w CuO NP scaffold reveals the highest level of tube formation in HUVEC cells and also upregulates the pro‐angiogenesis genes (VEGFA and bFGF) expression with no cytotoxicity effects. The presence of SSA and its interaction with CuO NP, and also core‐shell structure sustain the release of the nanoparticles and provide a non‐toxic microenvironment for cell adhesion and tube formation, with no sign of adverse immune response in vivo. The optimized scaffold significantly accelerates diabetic wound healing in a rat model. This study strongly suggests the 0.8%w/w CuO NP‐loaded PCL/SSA‐PVA as an excellent diabetic wound dressing with significantly improved angiogenesis and wound healing.