Transcriptional analysis of the healing response of wounded nerves treated with collagen and silicone tubes

This study examines the transcriptional differences between nerve wounds treated with silicone tubes and those treated with collagen nerve regeneration templates. The primary motivation for the study is to test the hypothesis that the discrepancy between the low-quality regenerate that forms in a silicone tube and the high-quality regenerate that forms in a collagen tube is due to differences in gene transcription. We used in vivo experiments on rat sciatic nerves with the use of real-time PCR to study the mRNA expression levels of certain inflammatory cytokines and contractile proteins after injury in both silicone-treated and collagen-treated nerve wounds. The contents of the wound site were analyzed on days 1, 3, 7, 14, and 21 following injury. The results of this experiment showed that although a difference in mRNA expression of a-SM actin is significantly higher at later time points in silicone-treated wounded nerves as compared to collagen-treated wounded nerves, there is little or no significant difference in the mRNA expression of TGF-P 1, TGF-P2, and TGF-P3 in wounds from the two devices. This suggests that the presence of a collagen regeneration nerve template does not direct the wound healing process at a transcriptional level. Thesis Supervisor: loannis Yannas Title: Professor of Polymer Science and Engineering Acknowledgements First and foremost, I give all the glory of this accomplishment to God, my Lord and Savior. He has blessed me with the opportunity to tackle this endeavor, and only by His provision have I been able to provide even a small contribution to this field. I would also like to thank my parents for providing so much love and encouragement throughout not only my graduate studies but also my entire life. Without their devotion to me, their desire to provide me every opportunity in life, and their continual support throughout all of my endeavors, graduate school and this work would not have been possible. Additionally, I want to thank my aunts and uncles here in Boston who have also poured out so much love and practical support to me throughout my years at MIT and have made these years much more enjoyable. Special thanks also go to Shutsu Chai for all that she has done to support me during my undergraduate and graduate work. She has made the long nights of study and research much more bearable and even enjoyable through her presence and encouragement. Next, I want to thank Professor Yannas for his role as my academic and thesis advisor, for his concern for my personal well-being, goals, and desires, and for his understanding in all of my academic pursuits. The rest of the Fibers and Polymers lab has also given me much assistance in this project and making our lab such a fun place to work. I especially thank Eric for all that he has contributed by preparing the implant devices, performing the surgeries, and general assistance in experimentation and data analysis. Further thanks go to Dr. Murphy and his lab at the Brigham and Women's Hospital for providing the equipment and lab space needed to perform many of these experiments. Special thanks to Qian Zhan for all of her help in supervising my activities and taking care of me at the Murphy Lab. In addition, I thank Dr. Myron Spector and Dr. H-P Hsu for their help in performing the animal surgeries. I want to also thank my church for providing a spiritual home here in Boston without which this entire project would be meaningless to me. As a Christian, my personal relationship with God comes above all else. I specifically want to thank Pastor Paul and Becky JDSN for their role in starting the church, the MIT group for their continual support throughout my years here, and Heechin JDSN and the rest of the young adult department for continuing to provide spiritual and physical support and guidance and for teaching me the difficulties and meaning of love. Also, special thanks to some of my friends who have prayed for me and encouraged me along the way. Kyle for being an awesome friend, Vallent for thinking about useless things with me, Abe for reminding me life should be simple, Adam for being my long-time bro, Orton, Austin, and Saji for being like older brothers to me, Bryan for biking with me, Sam for inspiring me to not settle for mediocrity, Yu for his long-distance prayers, the guys at C2 and C3 for their prayers, the list goes on and on. Lastly, I want to thank NIH for the funding for this project as well as the Massachusetts Institute of Technology for my years spent here as an undergraduate and graduate student. It has been a wonderful experience and an amazing opportunity.