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Title: Self-assembled functionalised peptides for small-diameter vascular graft applications
Author: Samman, Fatimah Basem
ISNI:       0000 0004 7230 0571
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2017
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Current clinically used small-diameter vascular grafts have been shown to have poor patency rates mainly caused by thrombus formation due to the absence of the anti-thrombogenic endothelium. Studies of novel small-diameter decellularised porcine arteries in large animal models of vascular replacement have also shown poor patency rates. The aim of this study was to develop a series of bioactive self-assembled P11 peptides as surface coatings to enhance re-endothelialisation of decellularised porcine external iliac arteries and potentially mitigate thrombus formation. Porcine external iliac arteries were decellularised and validated for acellularity and in vitro biocompatibility. These acellular scaffolds lacked the natural anti-thrombogenic endothelium lining the arterial lumen. The peptides P11-4, P11-8 and P11-12 were studied at different concentrations under physiological conditions using Fourier transform infrared spectroscopy and transmission electron microscopy as possible candidates for surface coatings. The peptides in their monomeric state were tested for anti-thrombogenic properties using a Chandler loop model. Self-assembly of peptides within acellular arteries was then assessed for the ability to form surface coatings by scanning electron microscopy, fluorescent microscopy and multiphoton laser scanning microscopy. P11 peptides were functionalised with bioactive cell attachment motifs (GRGDS and YIGSR) using copper catalysed azide-alkyne click chemistry. These motifs are found in extracellular matrix proteins and can be recognised by endothelial cell integrins. The effect of functionalisation on cell attachment of isolated ovine femoral endothelial cells onto acellular artery was assessed by live/dead® assay for 72 hours. The results showed that decellularisation of porcine external iliac arteries was reproducible with preserved extracellular matrix and DNA reduction of > 97 %. P11-4, P11-8 and P11-12 at 20 mg.mL-1, were shown to have high β-sheet proportions and the former two peptides were shown to form self-supporting gels almost instantaneously. P11-4 and P11-8 were shown to have anti-thrombogenic properties when present in blood potentially reducing thrombus formation. Moreover, the two peptides were shown to coat the extracellular matrix structures of the luminal surface of decellularised porcine external iliac arteries. In vitro, the bioactive peptides GRGDS-P11-4 and YIGSR-P11-4 were shown to enhance cell attachment and retention when compared to the corresponding scrambled control coatings, non-functionalised P11-4 coatings and uncoated acellular arteries. To conclude, the use of bioactive self-assembling peptides is a promising approach for improving the functionality of acellular arterial xenografts.
Supervisor: Warriner, Stuart ; Ingahm, Eileen ; Wilshaw, Stacy-Paul Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available