17 research outputs found

    Electrospun PGA/gelatin nanofibrous scaffolds and their potential application in vascular tissue engineering

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    Hadi Hajiali1, Shapour Shahgasempour1, M Reza Naimi-Jamal2, Habibullah Peirovi11Nanomedicine and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences; 2Department of Chemistry, Iran University of Science and Technology, Tehran, IranBackground and methods: In this study, gelatin was blended with polyglycolic acid (PGA) at different ratios (0, 10, 30, and 50 wt%) and electrospun. The morphology and structure of the scaffolds were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The mechanical properties were also measured by the tensile test. Furthermore, for biocompatibility assessment, human umbilical vein endothelial cells and human umbilical artery smooth muscle cells were cultured on these scaffolds, and cell attachment and viability were evaluated.Results: PGA with 10 wt% gelatin enhanced the endothelial cells whilst PGA with 30 wt% gelatin increased smooth muscle cell adhesion, penetration, and viability compared with the other scaffold blends. Additionally, with the increase in gelatin content, the mechanical properties of the scaffolds were improved due to interaction between PGA and gelatin, as revealed by Fourier transform infrared spectroscopy and differential scanning calorimetry.Conclusion: Incorporation of gelatin improves the biological and mechanical properties of PGA, making promising scaffolds for vascular tissue engineering.Keywords: polyglycolic acid, gelatin, nanofiber, vascular tissue engineering, biocompatible scaffold&nbsp

    Discovery of Cephalosporin-3'-Diazeniumdiolates That Show Dual Antibacterial and Antibiofilm Effects against Pseudomonas aeruginosa Clinical Cystic Fibrosis Isolates and Efficacy in a Murine Respiratory Infection Model.

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    The formation of biofilms provides a formidable defense for many bacteria against antibiotics and host immune responses. As a consequence, biofilms are thought to be the root cause of most chronic infections, including those occurring on medical indwelling devices, endocarditis, urinary tract infections, diabetic and burn wounds, and bone and joint infections. In cystic fibrosis (CF), chronic Pseudomonas aeruginosa (P. aeruginosa) respiratory infections are the leading cause of morbidity and mortality in adults. Previous studies have shown that many bacteria can undergo a coordinated dispersal event in the presence of low concentrations of nitric oxide (NO), suggesting that NO could be used to initiate biofilm dispersal in chronic infections, enabling clearance of the more vulnerable planktonic cells. In this study, we describe efforts to create "all-in-one" cephalosporin-based NO donor prodrugs (cephalosporin-3'-diazeniumdiolates, C3Ds) that show both direct β-lactam mediated antibacterial activity and antibiofilm effects. Twelve novel C3Ds were synthesized and screened against a panel of P. aeruginosa CF clinical isolates and other human pathogens. The most active compound, AMINOPIP2 ((Z)-1-(4-(2-aminoethyl)piperidin-1-yl)-2-(((6R,7R)-7-((Z)-2-(2-aminothiazol-4-yl)-2-(((2-carboxypropan-2-yl)oxy)imino)acetamido)-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methoxy)diazene 1-oxide)-ceftazidime 12, showed higher antibacterial potency than its parent cephalosporin and front-line antipseudomonal antibiotic ceftazidime, good stability against β-lactamases, activity against ceftazidime-resistant P. aeruginosa in vitro biofilms, and efficacy equivalent to ceftazidime in a murine P. aeruginosa respiratory infection model. The results support further evaluation of AMINOPIP2-ceftazidime 12 for P. aeruginosa lung infections in CF and a broader study of "all-in-one" C3Ds for other chronic infections
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