Date of Award
Doctor of Philosophy (PhD)
Steven A. Jones
Cardiovascular disease is the leading cause of death in North America. Cardiac infarction caused by thrombus plaque rupture can often lead to sudden death. Arterial stenosis caused by atherosclerosis is an important precursor leading to thrombus formation. Shear stress, abnormal lipid metabolism, and subendothelial layer exposure are the major contributors to arterial thrombus formation. Platelet activation by the above factors, followed by adhesion is the basic sequence in thrombus formation.
Platelets were encapsulated with nanofilm in order to reduce platelet activation and adhesion under high shear stress. Polyions, nanoparticles and immunoglobulins were assembled in nano-organized shells on fixed bovine platelets through the electrostatic layer-by-layer (LbL) self-assembly technique. The coverage of 78-nm silica and 45-nm fluorescent nanospheres on platelets was studied under TEM or fluorescence microscopes. An IgG-layer was adsorbed on platelets in alternation with poly(styrenesulfonate), and its specific immune-recognition and targeting with fluorescent anti-IgG-FITC were demonstrated. Not only limited to fixed platelets, live platelets were also coated with polyions with a outermost layer of heparin. Most platelets were alive and not activated after the coating procedure and no obvious cytotoxicity was observed.
A coronary artery stenosis silicone model was built to test encapsulated platelet function under high shear stress generated by the stenosis. In the platelet activation study, encapsulated platelets released less TXB2 compared with unmodified platelets. Platelets with heparin coating were not that easily adhered onto collage substrate in silicone model after the flow experiment. The heparin shell might block the possible binding reactions between collagen and platelet surface glycoproteins.
In conclusion, the nano-engineered platelets expressed less activation and adhesion under high shear stress.
Ai, Hua, "" (2002). Dissertation. 699.