Abstract

Ischemic events associated with coronary heart diseases (CHD) are the leading cause of death worldwide for both genders. They are directly associated with restricted blood flow caused by accumulation of atherosclerotic plaque in vessel’s lumen. Percutaneous coronary intervention (PCI), including stent deployment, is currently considered as the dominant procedure for mechanically recovering myocardial perfusion to avoid lethal ischemic events. As vascular prosthesis, coronary stents suffer from two major and common complications; thrombosis and restenosis. Thrombosis is linked with insufficient migration of endothelial cells (EC) and proliferation at site of tissue injury. Restenosis is caused by unwanted proliferation of underlying vascular smooth muscle cells (VSMC). With drug eluting stents (DES) as a strategy to mitigate aforementioned complications, it only results in reducing VSMC proliferation. However, it directly causes poor endothlialization through undifferentiated inhibition of endothelial cells as well. This can result in high risk of late thrombosis, leading to death. Different strategies are being investigated to reach optimum duration and conditions for endothelium healing as a critical aspect of enhancement for drug eluting stents. In this thesis, a nanoarchitectured system is proposed as surface enhancement for drug eluting stents. Highly oriented nanotubes were vertically grown on the surface of a biocompatible Ti-based alloys, as potential material for self-expandable stents. The fabricated nanoarchitectured system is self-grown from the potential stent substrate. This material is also proposed to enhance endothelial proliferation while acting as drug reservoir to hinder VSMC proliferation. Two morphologies were prepared to investigate the effect of structure homogeneity on the intended application. They were characterized for morphological investigation using Field-emission scanning electron microscope (FESEM), X-ray diffraction (XRD), Raman spectroscopy, Energy dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS). Nanoindentation technique was used to study the mechanical properties of the fabricated material. Cytotoxicity and proliferation studies were done and compared for the two fabricated nanoarchitectures versus smooth untextured samples using in-vitro cultured endothelial cells. Finally, drug loading capacity was investigated practically and supported by computational study of release profile using COMSOL® Multiphysics software.

Department

Nanotechnology Program

Degree Name

MS in Nanotechnology

Graduation Date

6-1-2015

Submission Date

May 2015

First Advisor

Allam, Nageh

Committee Member 1

El Sayyed, Mayyada

Committee Member 2

Salem, Hanadi

Extent

131 p.

Document Type

Master's Thesis

Library of Congress Subject Heading 1

Nanomedicine.

Library of Congress Subject Heading 2

Coronary heart disease -- Treatment.

Rights

The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy.

Institutional Review Board (IRB) Approval

Not necessary for this item

Comments

First I would like to express my sincere gratitude to my advisor, Dr. Nageh Allam for his ongoing support along the duration of my studies and research work. He has been a leading example for commitment and dedication to me and the whole group. He made me appreciate the process of learning more by time. He always reminded me why I love science through his passion towards it. I learned from you how to learn. Thanks a lot for everything. Am as well grateful for all my professors, who taught and guided me during the course of my studies within the Nanotechnology program. I would like to specially thank Dr. Hanadi Salem, Dr. Adham Ramadan and Dr. Mohab Anis. I learned a lot from your courses way beyond the educational content alone. I enjoyed the multidisciplinarity of the program, it certainly opened for me a lot of doors for future learning. I would like to thank the American University in Cairo for offering me a grant to finance my research work. Special thanks to Dr. Mohamed Gepreel from Egypt-Japan University of Science and Technology for supplying me with the alloy samples. I would like to also thank all my colleagues in EML group for their continuous support and motivation. Special thanks to Basamat for her kindness and guidance since the first day I joined the group, Mohy and Amer for their dedication to make sure the Lab is always supported, you are the group’s backbone, Salama for support with SEM imaging and Hafez with computational simulation. I am thankful for my colleagues at the STRC for their continuous support to my research work. Thank you so much Ghazaly Asmaa and Ehab. Also, researchers, chemists and friends at the Chemistry department. Isra, Yasmine, Samar, Ghada, Raghda, Ahmed Omaia, Mr. Emad and Mr. Mahmoud. I would like to express my endless appreciation to my parents and my sisters. To my father for his continuous support and encouragement. And to my sisters Haneen and Maram, my lifetime friends, companions and my backbone. I would love to take this opportunity to specially thank my mother, my number one teacher. I learned everything from her. I learned to work hard, to always seek to be better, to do my best and have faith in my capabilities. I am nothing without you, thanks for being always there for me and for everything. Rua, Worood, Shaimaa and Nada, I can’t thank you enough for your support and motivation. You are life time keepers and I wouldn’t have been able to go on without you. Although we didn’t work in one laboratory, but your fingerprints are all over everything I’ve done. AUC is not only granting me a degree, but also a gift of friends, who I will always be grateful to have. I am grateful to have a big support system of friend that have always believed in me and pushed me toward achieving my goals. Samar, Rana, Mai, Lana and Aya thank you for always being there for me in every aspect of my life and for making me always remember what life is actually about. Last but definitely not by any means the least, I would like to specially thank Mahmoud for being the inspiration behind the thesis topic, for giving me guidance, supporting me every single day, and offering me a blessing of having someone to always rely on. You give me confidence, comfort and energy. Thank you for being my best friend.

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