en Bionanotechnology Bionanotechnology مقاله پژوهشی Original Research Article <p style="direction: ltr; font-style: normal; text-align: justify;"><span style="display: none;">&nbsp;</span><span style="display: none;">&nbsp;</span><span style="font-size:16px;"><span style="font-family:Times New Roman;"><strong><span style="background:#2D7F8F;"><span style="color:white;">&nbsp;Background & Objective:</span></span> </strong>The combination of two or more therapeutic agents and their synergetic impacts can be therapeutically effective against multifactorial diseases, such as diabetic foot ulcers. This study demonstrates the application of a nanofiber-based drug delivery system with a controlled release of the growth factor. Various studies have shown that vascular endothelial growth factor<strong> (</strong>VEGF) stimulates angiogenesis via the VEGF signaling pathway and graphene oxide (GO)&nbsp;has been reported to possess antibacterial property<span dir="RTL">.</span> Therefore, VEGF and GO are hypothesized to have wound-healing effects when used synergistically.</span></span><br> <span style="font-size:16px;"><span style="font-family:Times New Roman;"><strong><span style="letter-spacing:-.1pt;background:#2D7F8F;"><span style="color:white;">&nbsp;Materials & Methods:</span></span></strong> &nbsp;In this study, VEGF was purified and verified by western blotting. GO and polycaprolactone (PCL) were prepared by electrospinning and were characterized by scanning electron microscope. Next, VEGF was immobilized by EDC/NHS linker in PCL-GO. <em>Staphylococcus aureus</em> and <em>Escherichia coli</em> were used to evaluate the antibacterial property of GO. Biodegradation and other release properties of the nanofibers were assessed. Moreover, the nanofibers were studied for cell viability and gene expression using human umbilical vein endothelial cells.</span></span><br> <span style="font-size:16px;"><span style="font-family:Times New Roman;"><strong><span style="background:#2D7F8F;"><span style="color:white;">&nbsp;Results: </span></span>&nbsp;</strong>The re-analysis of the protein-protein interaction network from the GO database confirmed the centrality of the nitric oxide synthase 3 (eNOS) showing its effects on the expression of other proteins. In addition, the PCL-GO nanofiber loaded with VEGF was studied for the expression of the <em>eNOS</em> gene in the VEGF signaling pathway. It was observed that PCL-GO-VEGF led to an increased expression of the <em>eNOS</em> gene in two weeks.</span></span><br> <span style="font-size:16px;"><span style="font-family:Times New Roman;"><strong><span style="background:#2D7F8F;"><span style="color:white;">&nbsp;Conclusion: </span></span></strong>&nbsp;&nbsp;Based on the observed antibacterial property and angiogenesis influence, PCL-GO-VEGF can be considered as a candidate to promote diabetic wound healing.</span></span></p> <p style="text-align: justify;"><p style="font-style:normal;"></p><p style="font-style:normal;"></p></p> <p style="text-align: justify;"><p style="font-style:normal;"></p></p> <p></p><p style="font-style:normal;"></p><div style="direction: ltr;"></div><div style="direction: ltr;"></div><p style="font-style:normal;"></p><div style="direction: ltr;"></div> <div style="direction: ltr;"><span style="font-size:14px;"><span style="display: none;">&nbsp;</span></span></div> <div style="direction: ltr;"><strong><span style="display: none;">&nbsp;</span></strong></div> Graphene oxide, Nanofiber, Nitric oxide synthase type III, Polycaprolactone, VEGF-A 152 160 http://journal.zums.ac.ir/browse.php?a_code=A-10-5468-1&slc_lang=en&sid=1 Ghader Nuoroozi gnworoozi66@gmail.com 5200319475328460056488 5200319475328460056488 No Dept. of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Meisam Omidi Maysam.omidi@gmail.com 5200319475328460056489 5200319475328460056489 No Protein Research Center, Shahid Beheshti University, Tehran, Iran Masoumeh Rajabibazl rajabibazl_m@yahoo.com 5200319475328460056490 5200319475328460056490 Yes Dept. of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Reyhaneh Hoseinpoor reyhanehoseinpour@yahoo.com 5200319475328460056491 5200319475328460056491 No Dept. of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran