Muscle-powered Soft Robotic Ventricular Assist Devices Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Engineering Jooli Han B.E., Biomedical Engineering, State University of New York M.S., Biomedical Engineering, State University of New York Carnegie Mellon University Pittsburgh, PA November 2020 © Jooli Han, 2020 All Rights Reserved Acknowledgements I am thankful for everyone that took parts in this meaningful journey towards a doctorate degree. I would like to thank my doctoral advisor, Professor Dennis R. Trumble, Ph.D., for his guidance in academics and in life throughout my time here at Carnegie Mellon University. He pushed me forward by living an example and sharing bits of life wisdom. It has been a privilege to have a caring, warm-hearted mentor who supervises his lab with great respect. Thanks to his unfailing patience and support, I was able to maintain a high standard of excellence and forge my own path independently. I would like to thank my thesis committee members for ensuring my research in the right direction. Professor Keith E. Cook, Ph.D. and Professor Conrad M. Zapanta, Ph.D. from Biomedical Engineering Department, Professor Carmel Majidi, Ph.D. from Mechanical Engineering Department, and Dr. Michael Scott Halbreiner, M.D. from Allegheny General Hospital generously shared their time and expertise. Without their critical questions and opinions, this thesis would not have been completed. I cannot express how lucky I am to have been a part of the Biomedical Engineering Department of Carnegie Mellon University. Thank you, faculty and staff, especially Maryia, Keri, Misti, and Kristin, for making the friendly and supportive environment to live in every day. This work would not have been possible without collaborations with Flexial Corporation – thank you, Greg Peters – and Professor Sung Hoon Kang, Ph.D.’s lab from Mechanical Engineering Department at Johns Hopkins University – thank you, Professor Kang and Ozan Erol, Ph.D. I would also like to thank National Institutes of Health for funding this project (NIH R01 37124.1.1090440). Thank you, Professor Wei Yin, Ph.D. and Professor David A. Rubenstein, Ph.D. from Biomedical Engineering Department at Stony Brook University for shaping me into a young scientist. Thank you, Professor Boyle Cheng, Ph.D., for being the best professor to TA for. Thank iii you for giving me opportunities to lecture, guide, and interact with students as a graduate teaching assistant. Thank you, Mrs. Powell, Mrs. Ganus, and Coach Cordero from Arlington High School. I was fortunate to receive the Innovation Fellowship (180145.620.284.100000.01) supported by Tepper School of Business at Carnegie Mellon University. But more importantly, I was privileged to have met and been mentored by great people as an Innovation Fellow. Thank you, Reed McManigle, J.D. from CMU Center for Technology Transfer and Enterprise Creation, for your entrepreneurial mentorship and legal and regulatory guidance. Thank you, Seth Boudreaux, Ph.D., for legal consultation and patent filing. Many thanks to EIRs including Lynne E. Porter, M.D., Melanie Simko, Kit Needham, and MaryDel Brady. I am deeply grateful for my friends and community that supported me through the toughest times. Special thanks to the people without whom this journey utterly would not have been possible. Thank you, my lab mates – Elaine Soohoo, Ph.D., Edgar Aranda-Michel, and Matthew Kubala – for your insightful comments and hard work. My office and lab neighbors made coming into work truly joyful every day. Thank you, Angela Lai, Ph.D., Rei Ukita, Ph.D., Suji Shin, Erica Comber, Deepshikha Acharya, Alex Rüsch, Ph.D., Sahil Rastogi, Ph.D., Raghav Garg, and more BME peeps. I would also like to thank my Korean friends for the precious memories in Pittsburgh. Thank you, Hyokyung Kim, Youngjoo Son, Haewon Jeong, Ph.D., Yunsik Ohm, Wooshik Kim, Hyung Woo Kim, Kiwan Maeng, Jungeun Kim, Sungho Kim, Ph.D., Suyoun Kim, Ph.D., Min Kyung Lee, Ph.D., Junsung Kim, Ph.D., Seungwhan Moon, Ph.D., SunJeung Yoon, Hyegyeong Park, Ph.D., Minji Yoon, Daye Nam, and many more. Thank you, Phil Phelps for the awesome CBT. Finally, I would like to express my greatest gratitude to my family. Thank you for being the best sister, Gyuri Han. Thank you, mom (Hyunjoo Lee) and dad (Youngsik Han), for your boundless love and endless support. 감사하고 사랑합니다. iv Abstract Congestive heart failure (CHF) remains one of the most costly diseases in the industrialized world, both in terms of healthcare dollars and the loss of human life. This epidemic is responsible for over $40 billion dollars per year in medical costs and lost productivity, and worse, 280,000 deaths each year in the U.S. alone. Despite great strides made in the treatment of CHF using mechanical ventricular assist devices, more than half of those who develop CHF die within 5 years of diagnosis. This is because conventional ventricular assist devices (VADs) continue to be extremely problematic with long term use due to infections caused by percutaneous drivelines and the persistent risk of clot formation associated with blood-contacting surfaces. To address both these longstanding problems, we have developed two types of completely implantable, non-blood-contacting circulatory support systems in this thesis work. An implantable muscle energy converter (MEC) was previously developed in this lab and operates by converting the contractile energy of the latissimus dorsi muscle (LDM) into hydraulic power that can be used to drive any pulsatile blood pump with power requirements consistent with steady-state MEC/LDM output capacity. The two main advantages of this implantable power source are that it significantly reduces infection risk by avoiding a constant skin wound created by percutaneous drivelines and improves patient quality-of-life by eliminating all external hardware components. In this thesis, we combined this unique biomechanical power source with 1) an extra-aortic balloon pump (EABP) to make a muscle-powered extra-aortic counterpulsation VAD (eVAD) and 2) a soft robotic direct cardiac compression sleeve (DCCS) to make a muscle-powered cardiac compression copulsation VAD (cVAD). The eVAD compresses the external surface of the ascending aorta during the diastolic phase of the cardiac cycle, offering increased cardiac output and improved coronary perfusion v without touching the blood. The MEC-EABP interface was designed to: 1) amplify MEC volume displacement to achieve proper balloon inflation, 2) maintain a secure and comfortable anatomic fit, 3) optimize energy transfer efficiency, 4) meet muscle force and speed requirements, 5) balance work storage and delivery for rapid balloon inflation/deflation, 6) minimize tissue/device reactivity, and 7) maximize device durability. The eVAD was then prototyped and bench tested to assess its viability as a long-term cardiac assist device. Results showed that the manufactured MEC-EABP system meets all seven design criteria listed above, demonstrating the overall feasibility of this approach. The cVAD represents an alternate approach to delivering muscle power via the MEC to boost cardiac output. Like the eVAD, this device supports the heart without touching the blood and so avoids the serious thromboembolic complications commonly associated with long-term VAD use. Unlike the eVAD however, which unloads the left ventricle indirectly via aortic counterpulsation delivered during cardiac diastole, the cVAD is designed to compress the epicardial surface of both ventricles during the systolic portion of the cardiac cycle, thereby providing support to both sides of the heart. Sleeve design was optimized via finite element analysis (FEA) simulations while biventricular deformations were simulated under various intra-ventricular and epicardial pressures to quantify the compression pressures required to achieve clinically significant improvements in cardiac performance. The sleeve material and manufacturing method were selected after a series of rigorous material testing and iterative prototyping processes. Results showed that a soft robotic sleeve 3D printed with ChronoSil meets all material and performance criteria for this application. Ultimately, whether the chosen approach is counterpulsation EABP or copulsation DCCS, these muscle-powered systems serve to both reduce the risk of infection and enhance patient vi quality-of-life by eliminating the need for external hardware components. Moreover, and of equal importance, using muscle power to actuate these non-blood-contacting pumps avoids thromboembolic events and obviates the need for long-term antithrombotic therapies. Therefore, these devices would, in principle, be a more attractive option for destination therapy as they would be simpler to maintain and hence less expensive in aggregate than traditional blood pumps, thereby resulting in wider availability and reduced costs for healthcare providers. vii Table of Contents Acknowledgments……………………………………………………………………..….……..iii Abstract………………………………………………………………………………….…..……v Table of Contents………………………………………………………………………………viii List of Tables………………………………………………………………………….….……..xiv List of Figures………………………………………………………………………..………….xv Chapter 1. Background and Significance ................................................................................... 1 1.1 The Need for Mechanical Circulatory Support ........................................................... 1 1.1.1 Congestive Heart Failure .........................................................................................