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Title: Next generation pre-polymer coatings to enhance in situ endothelialisation of vascular stents
Author: Pang, Jun Hon
ISNI:       0000 0004 7230 9891
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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The persistence of thrombosis and restenosis owing to inflammation and poor endothelialisation of cardiovascular stents in patients highlights the need for new biomaterials with in situ endothelialisation capability. This thesis describes the development of a novel chemical curing procedure using poly(carbonate)urethane pre-polymers (PCU-PP), and subsequent immobilisation of biomolecules to promote in situ endothelialisation. PCU-PP coatings were chemically cured with ethylenediamine (EDA), propargylamine (PPA) and 3-mercaptopropionic acid (MPA). Anti-CD34 antibodies, which can capture endothelial progenitor cells (EPCs), were immobilised on to EDA coatings (EDA-CD34Ab). Cyclic REDV peptides (cycREDV), which are ligands selective towards endothelial cells (ECs), were immobilised on to PPA coatings (PPA-cycREDV). EDA-curing yielded coatings with surface amine (-NH2) functionality alongside micro-ridges (~8 μm) and nanofeatures (~90 nm). MPA-curing yielded carboxyl (-COOH) functionalised coatings with submicron ridges (~0.5 μm), while PPA-curing produced alkyne (-C≡C) functionalised coatings with micro-islands (~15 μm) and nanofibrous morphology (< 120 nm). Human umbilical vein ECs (HUVEC) showed differential responses to these combinatorial chemistry and nanotopography platforms. Cell adhesion and proliferation were influenced primarily by surface chemistry, but were further regulated by nanotopography. Optimal cell adhesion and proliferation were impeded on EDA surfaces with 35 nm high nanofeatures, but was enhanced on 15 nm high nanofeatures. EDA-CD34Ab supported optimal adhesion and proliferation of HUVECs and endothelial colony forming cells (ECFCs), but reduced platelet adhesion and activation. ECFCs with higher CD34 expression demonstrated improved long-term survivability on EDA-CD34Ab. PPA-cycREDV enhanced HUVEC adhesion and survival compared to linear REDV chains, while also reduced platelet adhesion. Finally, combinatorial EDA-PPA curing yielded multifunctional coatings for co-immobilisation of anti-CD34Ab and cycREDV. The combined coatings did not show synergistic enhancement in HUVEC density, suggesting further optimisation in its formulation might be needed. In conclusion, PCU-PP was developed to produce coatings with tuneable chemistry and topography. Immobilisation of biomolecules enhances EC selectivity over platelets, which is vital to promote in situ endothelialisation and circumvent clinical complications including thrombosis and restenosis. The tailorability of combinatorial surface properties of such coatings is important for discovery of next generation biomaterials with pro-healing capabilities.
Supervisor: Cousins, B. ; Tsui, J. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available