Optimization and integration of nanosilver on polycaprolactone nanofibrous mesh for bacterial inhibition and wound healing in vitro and in vivo

Menglong Liu,1,2 Gaoxing Luo,1,2 Ying Wang,1,2 Weifeng He,1,2 Tengfei Liu,1,2 Daijun Zhou,1,2 Xiaohong Hu,1,2 Malcolm Xing,1,3 Jun Wu1,2,4 1State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, the Third Military Medical University, 2Department of Burns, Chongqing Key Laboratory for Disease Proteomics, Chongqing, People’s Republic of China; 3Department of Mechanical Engineering, University of Manitoba, Winnipeg, MB, Canada; 4Department of Burns, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China Abstract: Bacterial infection is a major hurdle to wound healing, and the overuse of antibiotics have led to global issue, such as emergence of multidrug-resistant bacteria, even “super bacteria”. On the contrary, nanosilver (NS) can kill bacteria without causing resistant bacterial strains. In this study, NS was simply generated in situ on the polycaprolactone (PCL) nanofibrous mesh using an environmentally benign and mussel-inspired dopamine (DA). Scanning electron microscopy showed that NS uniformly formed on the nanofibers of PCL mesh. Fourier transform infrared spectroscopy revealed the step-by-step preparation of pristine PCL mesh, including DA coating and NS formation, which were further verified by water contact angle changing from hydrophobic to hydrophilic. To optimize the NS dose, the antibacterial activity of PCL/NS against Staphylococcus aureus, Escherichia coli and Acinetobacter baumannii was detected by bacterial suspension assay, and the cytotoxicity of NS was evaluated using cellular morphology observation and Cell Counting Kit-8 (CCK8) assay. Then, inductively coupled plasma atomic emission spectrometry exhibited that the optimized PCL/NS had a safe and sustained silver release. Moreover, PCL/NS could effectively inhibit bacterial infection in an infectious murine full-thickness skin wound model. As demonstrated by the enhanced level of proliferating cell nuclear antigen (PCNA) in keratinocytes and longer length of neo-formed epidermis, PCL/NS accelerated wound healing by promoting re-epithelialization via enhancing keratinocyte proliferation in infectious wounds. Keywords: polycaprolactone nanofibrous mesh, mussel inspired, nanosilver, anti-infection activity, wound healing, re-epithelializatio