Abstract

After vascular graft implantation, the most dreaded complication is a bacterial infection due to high morbidity (45%) and mortality rates (30%). The treatment is challenging due to the possibility of encountering antibiotic-resistant strains and the inability of drugs to penetrate the formed biofilms, which can be manifested even years after implantation. Polymer-based tissue-engineered vascular grafts (TEVGs) with antimicrobial properties might be a strategy to prevent infection. Polycaprolactone (PCL) was chemically oxidized to introduce carboxyl groups on the polymer backbone (PCL-COOH) and then in-situ functionalized with Polyethylene Glycol (PEG 4-Arm-NH2) and Buforin II (PPB). In parallel, magnetite-silver core-shell nanoparticles were synthesized and dispersed in a PCL/gelatin blend (75:25) (PGN). Solvent casting was then allowed for both polymers and functionalization was confirmed via Fourier-transformed infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA). Metabolic activity (MTT) and hemolysis assays were performed to validate biocompatibility. Antimicrobial tests were conducted by a disc diffusion assay and a leachate toxicity assay using S.aureus and E.coli cultures. Physicochemical characterization showed effective polymer functionalization with PPB, as well as homogeneous nanoparticle incorporation in the PGN blend. Antimicrobial activity against S.aureus and E.coli was found for both polymers along with high cell viability (> 80%) and low hemolytic behavior (<5%), indicating high biocompatibility and hemocompatibility. The strategy proposed here holds much promise for long-term infection control as PCL is the most frequently used polymer for TEVGs fabrication.

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