Professor Y. C. Fung has made superb contributions to science, engineering, and humanity through his research and its applications, as well as his words and deeds. By setting the highest standards of rigor and excellence, training many outstanding students and their students, and providing his exemplary leadership, Dr. Fung has made tremendous impacts that spread across the world and transcend time. He established the foundations of biomechanics in a variety of living tissues, including the lung, the heart, blood vessels, blood cells, ureter, intestine, skin, as well as other organs and tissues. Through his vision of the power of “making models” to explain and predict biological phenomena, Dr. Fung opened up new horizons for bioengineering, from organs/systems to molecules/genes. He has initiated and fostered the research activities in many institutions in the U.S. and elsewhere in the world. He has made outstanding contributions to education in bioengineering, as well as service to the professional organizations and translation to industry and clinical medicine. He is widely recognized as the Father of Biomechanics and the leading Bioengineer in the world. His extraordinary accomplishments and commands in science, engineering, and the arts make him a Renaissance Man whom the world is most fortunate to have.
Hundredth birthday is a magnificent occasion of celebration for anyone who can attain this marvelous landmark. It is particularly special for Dr. Fung, because of his unparalleled accomplishments and contributions to humankind, benefitting each and every one of us in many ways. He is the greatest biomechanician and bioengineer, and his Centennial calls for very special celebrations. His friends, colleagues, students, and admirers are holding symposia, writing papers, organizing parties, and sending greetings to express our warmest feelings for this marvelous man. A special issue of the Journal of Medical Biomechanics was published in the celebration of Dr. Fung's 100th birthday . This article is based on my tribute to Dr. Fung on his 90th Birthday . I have written another article celebrating Dr. Fung's 100th Birthday to be published in Molecular Cellular Biomechanics . It is indeed my pleasure and honor to write this article to express my deepest admiration and most sincere congratulations!
Early Education and Contributions to Aeronautics
Dr. Fung was born on Sept. 15, 1919 in Yuhong, Wuxi, Kiangsu, China. He received his B.S. (1941) and M.S. (1943) in Aeronautics from the Central University, graduating at the top of his classes. After working as a Research Fellow at the Bureau of Aeronautical Research in Chengdu (1943–1945), Dr. Fung came to the U.S. to study for his Ph.D. in Aeronautics and Mathematics at California Institute of Technology (CalTech). He completed his doctoral study in less than 3 years and received his Ph.D. degree (Summa Cum Laude) in 1948. He stayed at CalTech as a Research Fellow in Aeronautics and advanced through Assistant and Associate Professors to become a Full Professor in 1959. At CalTech, Dr. Fung had outstanding research accomplishments on airplane dynamics in turbulent weather and safety, as well as performance and design of aircraft and spaceship. He wrote a definitive textbook on Aeroelasticity , which is still used broadly.
In late 1950s, because his mother was afflicted with glaucoma, Dr. Fung became interested in the mechanics of the eye, and later, the application of mechanics to other biological systems. He had the vision that if the structure and mechanical properties of a living organ can be determined, then the functions of that organ can be predicted by the principles of physics. He organized a landmark symposium on Biomechanics in 1966 .
In 1966, Dr. Fung and Dr. Benjamin Zweifach were recruited to UC San Diego, and they started a new Bioengineering Program, with biomechanics and microcirculation as the central themes. In 1980s, Dr. Fung created a new direction for bioengineering in “tissue engineering” to use engineering principles and techniques to repair, regenerate, or replace tissues. Tissue engineering has become the focus of bioengineering efforts in many programs in the world and has given rise to Regenerative Medicine. Thus, Dr. Fung has played a major role in two important disciplines, viz., biomechanics and tissue engineering, which have been the major thrusts in bioengineering.
Dr. Fung's contributions to biomechanics are immense. He created the field by combining his superb expertise in engineering mechanics with path-setting work in biomedical sciences for applications to important clinical problems. He integrates biology and mechanics at different scales, from organs/systems to molecules/genes. He correlates structure and function in terms of growth, geometry, and remodeling, with emphasis on temporal and spatial features as well as active versus passive responses. He combines experiments (performed with innovative technology and rigorous execution) and theory (formulated with creative formulation and elegant analysis) with effective iteration and feedback. He has established the foundation of biomechanics in the lungs, heart, blood vessels, skin, as well as other organs and tissues. He is recognized as the Father of Biomechanics. Most of Dr. Fung's publications have been collected in a two-volume treatise entitled “Selected Works on Biomechanics and Aeroelasticity” , which provides a very valuable reference resource. A very brief introduction to his immense contributions is given in this paper.
Red Blood Cells and Microcirculation
Dr. Fung investigated the mechanics and geometry of human red blood cells (RBCs) by using elegant engineering analysis and innovative experimental approaches. These included stress analysis in RBC swelling , determination of RBC 3D geometry by interference microscopy (Fig. 1) , and the use of extreme theorem to analyze the extreme value statistics of RBC geometry .
Dr. Fung studied the behavior of blood cells in blood vessels, especially at the branch points. He used experimental studies and engineering analysis to elucidate the mechanism of stochastic nature of flow in capillaries. He showed that a small difference in flow at a bifurcation can cause a dramatic nonlinear effect on the distribution of blood cells between two daughter branches  (Fig. 2). With the use of a lab model system, he demonstrated the important role of RBCs in modulating the interaction of white blood cells (WBCs) with the vascular endothelial cells (ECs) . He showed how high RBC concentration can push the WBCs toward the vessel wall to enhance WBC-EC interactions. These findings have important implications on the hemodynamic modulation of WBC behavior in the microcirculation in health and disease, including inflammation.
Dr. Fung computed the blood flow pattern in vessels beyond a local constriction  and demonstrated that the complex flow behavior in such regions, including flow reversal, reattachment, and stagnation (Fig. 3), has major effects on EC structure and function and may thus play a significant role in atherogenesis.
Dr. Fung has made outstanding contributions on the interplay of circulatory and respiratory systems at the microcirculatory level. In pioneering work with Dr. Sidney Sobin and other colleagues [13,14] with rigorous experiments and elegant analysis, he formulated the innovative concept of sheet flow through the pulmonary capillaries between the posts that span sheets of the alveolar wall (Fig. 4). This sheet-flow theory has been applied to compute the alveolar sheet thickness and the alveolar sheet flow as a function of the pressure differential between the capillary and the alveolus (Fig. 5) . Application of this theory to experimental data provides a quantitative understanding of the interplay among many factors, including alveolar blood flow and blood volume, their regional differences, and transit time distributions, thus allowing the computation of the effects of flow on arterial, alveolar and venous pressures, alveolar area, mean A–V path length, and alveolar membrane tension . These findings opened up a new frontier for research on the pulmonary microcirculation in health and disease. Dr. Fung applied morphometric technique to study the topographical arrangements of arterioles and venules in the cat lung , and generated novel findings on the difference in distribution patterns between them (Fig. 6). He discovered that each terminal precapillary arteriole supplies an average of 24.5 alveoli and each terminal postcapillary venule drains an average of 17.8 alveoli.
Dr. Fung also applied morphometric analysis to determine the geometric features of the coronary artery circulation in the right ventricle of the pig under normal and hypertensive states . These results have generated important information on coronary artery remodeling in cardiac hypertrophy.
Residual Stress and Vascular Remodeling
One of Dr. Fung's very fundamental and innovative contributions is his research on residual stress, which is the stress that remains after the removal of external forces. He developed the ingenious approach by using the opening angle after cutting open a biological structure in two different directions to determine the residual stress. An example is shown in Fig. 7. An aorta was removed to be devoid of pressure load; after obtaining a ring by cross cuts, it was cut open in the radial direction to result in a zero stress state . The opening angle provides a measure of the residual stress in the vessel wall due to the geometry and wall constituents. It is truly amazing that an extremely important biomechanic parameter can be measured with such a simple experimental procedure, requiring only a pair of scissors!
Figure 8 shows the strikingly different residual stress between ileal artery and ileal vein as indicated by their opening angles . This opening angle measurement can also be applied to the heart ventricles , trachea , and other organs and tissues.
Dr. Fung's pioneering work on residual stress led him to formulate the concepts that the remodeling of a blood vessel is best described by changes of its zero-stress state and that growth results from changes in cellular and extracellular mass and configuration (Fig. 9) . These concepts led to the design of specific ways to test the biomechanical properties of a tissue-engineered vascular graft in order to match the hemodynamic conditions encountered in vivo.
With a combination of experimental and theoretical approaches, Dr. Fung has determined the 3D stress distribution in an artery  and also the stress–strain relations of collagen and elastin (Fig. 10) [25,26], two important interstitial constituents of the vessel wall.
These results led to the elucidation of the relationship of the biomechanical behavior of a blood vessel to its molecular constituents, thus contributing to the role of chemical composition to tissue remodeling. Dr. Fung established “Fung exponential strain energy function” which is widely used.
Dr. Fung conducted a systematic study on the time course of the remodeling of pulmonary arteries of normal and hypertensive rats in response to hypoxia (Fig. 11) . By using the deoxyribonucleic acid microarray technology to investigate changes in gene expression under such hypoxia-induced pulmonary hypertension , he was able to match the time course of changes in the expression of a number of genes with the alterations of specific structures and functions in the pulmonary artery, as exemplified in Fig. 12. This pace-setting study provides a genetic correlate of the functional abnormalities in pulmonary hypertension. Based on these and other findings, Dr. Fung proposed that “deoxyribonucleic acid replication and transcription involve molecular motion through a viscous medium to reach the appropriate site, and the lengthening takes place through the balance between the chemical energy of binding and the kinetic energy of molecular motion. Therefore, these processes involve accelerations, strains and strain rates with directions. They need to be treated as force vectors and stress tensor.”
Translation of Biomechanics to Technology, Industry, and Clinical Medicine
Dr. Fung's outstanding research was aided by the sophisticated instrumentation he developed to meet the experimental needs. Examples are the innovative device “Biodyne”  for testing the mechanical properties of a variety of biological materials (Fig. 13) and the instrumentation to study skin biomechanics , peristaltic transport [30,31], and peeling force in a biological graft . Dr. Fung's research formed the foundation of industrial applications in a variety of bioengineering fields, including the tissue engineering of cardiovascular, urinary, musculoskeletal, and cutaneous systems. His studies on the biomechanics of the skin played a significant role in the development of skin substitutes to treat burn patients. He contributed to the development of tissue-engineered vascular graft with mechanical matching to the native vessels. His research has led to the advancement of diagnosis and the treatment of a variety of important diseases, including pulmonary disorders such as pulmonary hypertension and emphysema, cardiovascular diseases (myocardial infarction, heart failure, atherosclerosis, and systematic hypertension), dysmotility of the digestive and urinary systems, and musculoskeletal disorders. His important translational contributions led to his winning of the prestigious Fritz J. and Dolores H. Russ Prize from the NAE for “advancing science and engineering, ultimately improving the human condition,” specifically “for the characterization and modeling of human tissue mechanics and function, leading to prevention and mitigation of trauma.”
Dr. Fung has made outstanding contributions to bioengineering education as well as research. At UCSD, he built the superb graduate and undergraduate programs that have educated bioengineers making important contributions to bioengineering endeavors in universities, medical schools, hospitals, and industry. A large number of his students and postdoctoral fellows hold key faculty positions in universities and industries in the U.S. and abroad, and many are heads of departments of bioengineering. In the most recent National Academy of Sciences—National Research Council survey of graduate education published in 2010, UCSD Bioengineering was ranked number 1 in biomedical engineering. Professor Fung's vision and leadership played a significant role in this accomplishment.
Dr. Fung's educational influence extends beyond his excellent teaching in the classrooms and laboratories at UCSD. He defined the pedagogy of biomechanics by writing authoritative books (e.g., see Refs. [33–35]) that are widely used as textbooks in U.S. and abroad and are read virtually by everyone in the field. These books have been translated into many foreign languages and updated in several editions, setting the standard for all textbooks in bioengineering. He has made great contributions to education and training in many countries, especially China, which is his homeland. He played a major role in the birth of biomechanics and biomedical engineering in China by training the leaders, giving lectures, and organizing meetings there (such as the China–Japan–U.S. Conference on Biomechanics that he initiated).
Dr. Fung is extremely devoted to the education of the younger generation. This is clearly illustrated by my personal experience when I was attending the Microcirculatory Society (MCS) meeting in Atlantic City in 1965 as an Assistant Professor at Columbia. When I went to a restaurant with my wife and two daughters for dinner, I saw Dr. Fung at a neighboring table with members of MCS Council and went over to say hello to him. Then, Dr. Fung came over to our table and sat down to chat with us (Fig. 14) for nearly an hour until the MCS Council members and we all left. At that time, I had met Dr. Fung only once very briefly. His kindness to spend time with the young people was really impressive and greatly appreciated. I still remember vividly that wonderful experience nearly 50 years later.
Services to Professional Organizations
Dr. Fung has great devotion to the advancement of Bioengineering, and he has served in many key positions in professional organizations. He was President of the American Academy of Mechanics and the Biomedical Engineering Society (BMES), Vice President of the International Society of Biorheology, and Chairman of the Third International Congress of Biorheology, the Second World Congress of Microcirculation, and the first China–Japan–U.S. Conference on Biomechanics. He was also Chairman of the Applied Mechanics Division in the American Society of Mechanical Engineers (ASME), U.S. National Committee for Biomechanics (now Honorary Chairman), and World Council for Biomechanics (now Honorary Chair). Dr. Fung has been a member of Microcirculatory Society Council, American Physiological Society Council of Circulation, American Heart Association Council on Basic Science, and World Congress of Biomechanics Steering Committee.
As a result of his outstanding contributions to biomechanics and bioengineering, Dr. Fung has received many awards and honors. He is a member of all three U.S. National Academies (National Academy of Sciences, National Academy of Engineering, and National Academy of Medicine). He is also a Foreign Member of the Chinese Academy of Sciences and a member of Academia Sinica (Taiwan).
Dr. Fung has received all the major awards in his fields of endeavor, including the Eugene Landis Award from Microcirculatory Society (1975), Theodore von Kármán Medal from American Society of Civil Engineers (1976), Lissner Award for Bioengineering from ASME (1978), Centennial Medal from ASME (1981), Worcester Reed Warner Medal from ASME (1984), Poiseuille Medal from International Society of Biorheology (1986), Excellence in Research Award from UCSD (1987), ALZA Award from BMES (1989), Timonshenko Medal from ASME (1991), Borelli Award from American Society of Biomechanics (1992), Lifetime Achievement Award from the Association of Chinese Scientists and Engineers of California (1992), Distinguished Alumnus Award from California Institute of Technology (1994), Melville Medal from ASME (1994), and Bioengineering Award from the Japan Society of Mechanical Engineering (1995).
Dr. Fung has received two of the most prestigious awards from the NAE: besides the Russ Prize mentioned above, he received the Founders Award (1988) for “outstanding engineering accomplishments by an engineer over a long period of time and of benefit to the people of the U.S.”
Dr. Fung received the U.S. National Medal of Science, which is the highest honor for scientists and engineers in the U.S., from President Bill Clinton in 2001 for his “outstanding contributions to knowledge in the physical, biological, mathematical or engineering sciences” (Fig. 15).
Dr. Fung is a Fellow of the American Academy of Mechanics, American Institute of Aeronautics and Astronautics, ASME, American Institute of Medical and Biological Engineering, and Cardiovascular Section of the American Physiological Society. Dr. Fung is the recipient of Honorary Doctoral degrees and Honorary Professorships from many universities. He has been invited to give many named lectures and plenary lectures, and he is an Honorary Member of several scientific organizations.
In honor of Dr. Fung, the ASME established the “Y. C. Fung Young Investigator Award” in 1986; the Chinese Association of Biorheology, Chinese Society of Biophysics, International Society of Biorheology, and International Society of Clinical Hematology established the Chien-Fung Young Investigators Award; and UCSD established the Endowed Chair “Y. C. Fung Professor of Bioengineering” (Fig. 16).
A Renaissance Man
Dr. Fung and his lovely wife Luna Hsien-Shih Yu married in December 1949 in Pasadena, California (Fig. 17). Luna is an excellent mathematician with BS from Central University in China and MS from CalTech. They have two wonderful children Conrad and Brenda. After 68 years of a marvelous marriage, Luna unfortunately passed away in April 2017.
Conrad has two sons Anthony (Tony) and Michael, and Brenda has a son Nicholas Manos (Fig. 18). Tony finished his undergraduate study in Bioengineering at UCSD and is now enrolled in the graduate program. I have the pleasure of having him as a Teaching Assistant in the Introduction to Bioengineering course. He is intelligent, knowledgeable, creative, dedicated, and caring for the students, following the tradition of his grandfather. Michael is studying Neuroscience at Vanderbilt University and will apply for medical school next year. He is an avid opera singer and will sing in the Vanderbilt chorale in Prague this summer. Nick graduated from USC majoring in marketing. He lives in Long Beach with his wife Claire.
Dr. Fung is not only a superb scientist and engineer but also a wonderful artist. He has excellent commands in Chinese calligraphy and poetry. He has marvelous talents in making Chinese chops (or seals, usually for people's names); the imprints of these can be found in the front pages of many of his books. Thus, Dr. Fung excels in Science, Engineering, and Art. He is a renaissance man, a peer of Leonardo DaVinci (Fig. 21).
The author thanks the World Scientific Publishing, Co., Pte., Ltd, Singapore, for giving the permission to use the materials presented in Ref. .