Many of the materials used today for cardiovascular implants exhibit good bulk
mechanical properties but fail to provide desirable surface properties for reducing
thrombogenicity and promoting tissue integration. In fact, biological responses at the
blood-material interface, including non-specific protein adsorption, coagulation, and
platelet adhesion and activation significantly limit the use of currently available materials
in many blood contacting applications. As our understanding of the biological responses
to foreign materials has grown, so too has the potential for creating 'bioactive' materials
capable of inducing and directing beneficial cellular processes. One promising technique
for circumventing undesirable blood-biomaterial interactions involves seeding vascular
endothelial cells (ECs) onto synthetic vascular grafts as a means of exploiting the
physiological anticoagulant characteristics of the endothelium. Methods for improving
cell retention on these constructs include immobilization of cell recognition motifs on the
biomaterial surface in order to improve interactions between cells and the synthetic
substrate. However, there remains the need to better understand the interactions between
surface bound ligands and cells, and the role of linker molecule chemistry on ligand
bioactivity and cellular response. In the current work, a novel method was optimized for
modifying poly (dimethylsiloxane) (PDMS) with cell adhesion peptides tethered via a
heterobifunctional allyl-, NSC-terminated polyethylene oxide (PEO) linker molecule.
These novel surfaces combine the protein repellant property of PEO with the cell binding
property of cell adhesion peptides. It was found that surfaces modified in this manner
reduced protein adsorption to PDMS while increasing cell adhesion. Therefore the use of
a generic PEO linker molecule was shown to be a very promising method of reducing
non-specific protein interactions while maintaining ligand bioactivity.
Silicone surfaces were also modified with diaminobutane (DAB) dendrimers in an
attempt to increase the surface capacity for attachment of biomolecules and to compare
the effect of surface peptide density with ligand mobility. Grafting cell adhesion peptides
via surface bound dendrimers was found to increase the surface peptide density when
compared to peptides grafted via the PEO spacer alone. However, cell adhesion was not
significantly improved on the dendrimer-peptide modified surfaces compared to PDMS
controls. This observation provides evidence that the properties of the linker molecule
used for attachment of cell adhesion peptides to a biomaterial surface may be a critical
factor in determining peptide bioactivity. In this case the peptides bound to the surface
via the highly mobile linear PEO linker showed increased cell adhesion when compared
to peptides linked via the rigid, highly branched dendrimer. It is therefore hypothesized
that ligand mobility on a biomaterial surface may significantly influence ligand-cell
receptor interactions to an even greater extent than surface peptide density. / Thesis / Master of Applied Science (MASc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/23554 |
| Date | 07 1900 |
| Creators | Mikhail, Andrew S |
| Contributors | Sheardown, H, Jones, K.S., Chemical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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