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Currently used small diameter synthetic vascular grafts are prone to high rates of failure related to thrombosis and neointimal hyperplasia. Biomimetic materials, based on the extracellular matrix (ECM) composition of native tissues, represent an attractive solution to address these complications. The inherent low thrombogenicity and cell signalling properties of elastin-like polypeptides (ELPs) make them a suitable option for these applications. In this thesis, ELP surface modification has been achieved through the use of elastin cross-linking peptide bioactive fluorinated surface modifiers (ECP-BFSMs). The synthesis of these low molecular weight fluorinated additives was described and their subsequent blending with a base polycarbonate-urethane (PCNU) was shown to successfully enrich the surface to allow for ELP surface cross-linking. The kinetic surface migration of fluorescent ECP-BFSMs was studied over a 2 week casting period by two-photon confocal microscopy. Contact angle and x-ray photoelectron spectroscopy (XPS) confirmed the surface localization of the ECP-BFSMs. Changes in contact angle and XPS spectrums following ELP surface cross-linking confirmed the success of the surface modification approach. The novel ELP surface modified materials were demonstrated to inhibit fibrinogen surface adsorption and platelet adhesion under physiological flow conditions and inhibit bulk platelet activation following blood-material contact. Moreover, these ELP modified surfaces were shown to promote increased endothelial and smooth muscle cell adhesion, spreading and retention over a 7 day culture period relative to their non-ELP analogs. Endothelial and smooth muscle cells seeded on the elastin-like materials were shown to express endothelial nitric oxide synthase (eNOS) and smooth muscle myosin heavy chain (SM-MHC) cell specific phenotypic markers, respectively. Furthermore, competitive inhibition experiments revealed that initial smooth muscle cell adhesion to ELP surface modified materials was mediated through elastin-laminin cell surface receptors binding to VGVAPG peptide sequences on the ELP molecules. Hence, these materials may have broad applicability in cardiovascular applications, from blood contacting materials to scaffold structures for vascular graft tissue engineering. Furthermore, this surface modifying additive approach represents a versatile technique that can be custom tailored for various biomimetic applications to generate stable bioactive ECM-like surfaces retained onto a relatively inert fluorinated background.

Thesis (M.M.S.E.)--University of Delaware, 2008. / Principal faculty advisor: Kristi L. Kiick and John F. Rabolt, Dept. of Materials Science & Engineering. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references. Also available in print.

The work in this thesis can be divided into two sections, namely the study of delicious peptide, a food flavour and the antimicrobial peptide lactofenicin B. The main interest in these compounds is in terms of structure and conformation adopted in solution and how this relates to their mode of action. Delicious peptide was studied initially by 1H NMR spectroscopy for evidence of a specific solution structure. Results show that delicious peptide does not adopt a regular conformation in solution. Molecular dynamics simulations of this peptide show the flexibility of the peptide structure in solution. Quenched molecular dynamics simulations were used to search for low energy conformers of the peptide. The results suggest that the flavour of the peptide is produced by interaction of basic and acidic regions in the peptide. The work was extended to examine delicious peptide analogues with similar flavour characteristics. The results obtained suggest that similar interactions of basic and acidic regions occur for these peptides to produce a savoury flavour. The antimicrobial peptide Lactofemcin B was synthesised by Fmoc poly-amide synthesis. Problems with the synthesis occurred due to the protecting groups used for the five arginine residues present in the sequence. Predictive modelling studies on Lactofenicin B peptide, derived from bovine lactofenicin protein suggest that the peptide adopts a region of alpha-helical conformation in solution. The flexibility of the peptide was studied by molecular dynamics in solution and simulations of other environmental conditions were carried out by variation of electrostatic interactions using dielectric constants for membrane, TFE and water environments. The results suggest the beta-helical conformation is most stable in an environment such as trifluoroethanol, the peptide showing more flexibility in aqueous solution. Experimental results for the peptide confirm the flexibility of the peptide in solution. CD results show that lactofenicin B has no specific conformation in solution, although an beta-helical conformation is adopted in trifluoroethanol. The peptide also adopts a beta-sheet conformation in low concentrations of SDS micelle and therefore its conformation is dependant on environmental conditions. NMR studies show that the peptide, although flexible in solution, shows short-range NOE interactions that suggest a local beta-helical conformation may be present. However the overall conformation for the peptide is a flexible one.

No description available.

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