© 2021 Yen-Hao Hsu ALL RIGHTS RESERVED BIORESORBABLE STEREOCHEMICALLY DEFINED POLYMERS FOR TISSUE ENGINEERING AND WIRELESS BIO-INTEGRATED ELECTRONIC DEVICE APPLICATIONS A Dissertation Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy Yen-Hao Hsu March, 2021 BIORESORBABLE STEREOCHEMICALLY DEFINED POLYMERS FOR TISSUE ENGINEERING AND WIRELESS BIO-INTEGRATED ELECTRONIC DEVICE APPLICATIONS Yen-Hao Hsu Dissertation Approved: Accepted: _______________________________ ______________________________ Advisor Interim Director of SPSPE Dr. Matthew L. Becker Dr. Ali Dhinojwala _______________________________ ______________________________ Committee Member Interim Dean of the College Dr. Yu Zhu Dr. Craig Menzemer _______________________________ ______________________________ Committee Member Interim Director, Graduate School Dr. Chrys Wesdemiotis Dr. Marnie Saunders _______________________________ ______________________________ Committee Member Date Dr. Xiong Gong _______________________________ Committee Member Dr. Kevin A. Cavicchi iii ABSTRACT In most synthetic bioresorbable polymers, changing the physical properties such as elasticity and toughness by monomers results in a change to the crystallinity of the material, which manifests through alteration of its mechanical performance. “Thiol-yne” click chemistry has been discovered as an efficient methodology for step-growth polymerization between thiols and activated alkynes. Variation of the solvent polarity and base strength results in a series of elastomers possessing a wide variation of cis stereochemistry and crystallinity resulting in wide range of elasticity and stiffness. These materials are noteworthy that they do not rely on hard block-soft block interactions for their elastic properties nor are they crosslinked, which facilitates their degradation and use in regenerative medicine applications. Significantly, the crystalline domains that form between the cis alkene units and degradable segments to provide unexpected water barrier properties while retaining the ability to be resorbed. Thus, this innovation opens the new route for developing bioresorbable elastomers that can be widely applied into tissue engineering and wireless medical bio-electronics. iv DEDICATION I would like to dedicate this work to my wife, Yu-Chia Lai, who has sacrificed her past five years to allow me to pursue my education. You are my loyal listener, most trustworthy supporter, and my best friend. v ACKNOWLEDGEMENTS The completion of this work could not have been completed without the aid and assistance of many individuals. First, I would like to thank my advisor, Dr. Matthew Becker, for his support, guidance, and enthusiasm during my graduate studies. I especially am thankful for the room and the respect that he granted me during my graduate work. I would also like to thank my committee members, Dr. Yu Zhu, Dr. Xiong Gong, Dr. Chrys Wesdemiotis, and Dr. Kevin Cavicchi for spending their precious time giving me some suggestions and inputs. This work of this dissertation would not have been possible without the help and assistance of my fellow group members. I would like to especially acknowledge: Dr. Jiayi Yu, Shantanu Nikam, Yongjun Shin, Dr. Derek Luong, Dr. Jason Nettleton, Karissa Nettleton, Dr. Darya Asheghali, Dr. Alex Kleinfehn, Dr. Zach Zander, Dr. Nathan Dreger, Dr. Garrett Bass, and Peiru Chen. I will always cherish the memories and keep Becker lab championship attitude in my mind. Last, but not least, I would like to thank my family and friends. Their selfless love and continuous support have kept me focused and positive all the time. Each of you has helped me obtain my goals. vi TABLE OF CONTENTS Page BIORESORBABLE STEREOCHEMICALLY DEFINED POLYMERS FOR TISSUE ENGINEERING AND WIRELESS BIO-INTEGRATED ELECTRONIC DEVICE APPLICATIONS ............................. iii LIST OF TABLES .................................................................................................................... ix LIST OF FIGURES ................................................................................................................... x LIST OF SCHEMES .............................................................................................................. xxi CHAPTER1 I. INTRODUCTION ............................................................................................................ 1 1.1. Background for Synthetic Biodegradable Polymers ............................................ 1 1.2. Design and Synthesis of Biodegradable Ester-based Polymers ........................... 2 1.3. Synthetic Biodegradable Polymers via Thiol-yne Step-growth Polymerization .. 7 1.4. Biodegradable Elastomers as Encapsulation in Wireless Bioresorbable Medical Electronics .................................................................................................................. 10 II. MATERIALS AND INSTRUMENTATION ........................................................................ 12 2.1. Materials ............................................................................................................ 12 2.2. Instrumentation ................................................................................................. 13 III. CROSSLINKED INTERNAL ALKYNE-BASED STEREOELASTOMERS: POLYMERS WITH TUNABLE MECHANICAL PROPERTIES ................................................................................ 17 3.1. Abstract .............................................................................................................. 17 3.2. Introduction........................................................................................................ 18 3.3. Experimental ...................................................................................................... 20 3.4. Results and Discussion ....................................................................................... 30 3.5. Conclusion .......................................................................................................... 41 3.6. Acknowledgement ............................................................................................. 42 vii IV. SHAPE MEMORY BEHAVIOR OF BIOCOMPATIBLE POLYURETHANE ELASTOMERS SYNTHESIZED VIA THIOL-YNE MICHAEL ADDITION .......................................................... 43 4.1. Abstract .............................................................................................................. 43 4.2. Introduction........................................................................................................ 44 4.3. Experimental ...................................................................................................... 47 4.4. Results and Discussion ....................................................................................... 55 4.5. Conclusion .......................................................................................................... 65 4.6. Acknowledgement ............................................................................................. 66 V. BIORESORBABLE ELASTOMERS WITH TUNABLE CRYSTALLINITY AS ENCAPSULATION LAYER IN WIRELESS BIO-ELECTRONICS TO ENHANCE WATER BARRIER ........................... 67 5.1. Abstract .............................................................................................................. 67 5.2. Introduction........................................................................................................ 68 5.3. Experimental ...................................................................................................... 70 5.4. Results and Discussion ....................................................................................... 78 5.5. Conclusion .......................................................................................................... 85 5.6. Acknowledgement ............................................................................................. 86 VI. CONCLUSION .............................................................................................................. 87 REFERENCES ...................................................................................................................... 91 APPENDIX A-SUPPORTING FIGURES ............................................................................... 112 APPENDIX B-SUPPORTING SCHEMES .............................................................................. 164 viii LIST OF TABLES Table Page Table 3.1. Molecular masses, thermal and mechanical properties of internal alkyne-based (co)polymers, end-capped functionalized polymer, and crosslinked polymers. .............. 39 Table 4.1. Stereochemistry and molecular masses of thiol-yne polymers (U6T6) were obtained using different polymerization conditions from 5,14-dioxo-4,15-dioxa-6,13- diazaoctadecane-1,18-diyl dipropiolate (U6) and 1,6-hexanedithiol (T6) precursors and thermal properties were obtained by DSC. ...................................................................... 58 Table 4.2. Thermal and mechanical properties for five different %cis U6T6 polymers. ... 60 Table 5.1. Molecular masses, thermal and properties of (co)polymers with different molar fraction of bis(3-mercaptopropyl) succinate (CSS) incorporation. .................................... 82 Table 5.2. Mechanical properties of (co)polymers with different molar fraction of bis(3- mercaptopropyl) succinate (CSS) incorporation. ..............................................................