Regenerative Medicine: Current Concepts and Changing Trends
Anthony Atala Professor Wake Forest School of Medicine in North Carolina
Patients with diseased or injured organs may be treated with transplanted tissues. There is a severe shortage of donor organs and tissues which is worsening yearly due to the aging population. Regenerative medicine and tissue engineering apply the principles of cell transplantation, material sciences, and bioengineering to construct biological substitutes that may restore and maintain normal function in diseased and injured tissues. Stem cells may offer a potentially limitless source of cells, and 3D bioprinting applications are being utilized for potential therapies and body-on-a-chip technologies for drug discovery and personalized medicine. Recent advances that have occurred in regenerative medicine will be reviewed. Applications of these new technologies that may offer novel diagnostics and therapies for patients with tissue injury and organ failure will be described.
Dr. Anthony Atala, George Link Professor and Director of the Wake Forest Institute for Regenerative Medicine, is a practicing surgeon and a regenerative medicine researcher. His work focuses on growing human tissues and organs using cells and 3D Printing. He is Editor-in-Chief of three journals. He is a National Academy of Medicine and National Academy of Inventors member. His work has been listed twice as Time Magazine’s top 5 medical breakthroughs of the year and he was named by Scientific American as one of the world’s most influential people in biotechnology. He has received numerous awards for his work, including the Edison Science Award, the Smithsonian Ingenuity Award, and the R&D Innovator of the Year Award. More than 14 applications of his laboratory technologies have been used clinically. He is the editor of 20 books, has published over 600 journal articles, and has applied/received over 250 national and international patents.
Development of Conceptually New Fluorogens for Biomedical Applications
Ben Zhong Tang Cheong Professor of Science Chemical and Biological Engineering at The Hong Kong University of Science and Technology (HKUST, Kowloon)
Advanced biosensors are highly demanded for accurate biological detection and clinical diagnostics. Fluorescence (FL) is an essential signal for in situ visualization of bioanalytes at the molecular level and monitoring complex biological processes in real time. The red to near-infrared fluorescence could offer minimized autofluorescence interference in living systems. However, the performance of most traditional fluorophores is still limited by the photobleaching effect and moderate signal-to-noise ratio, and their applicability for in vivo imaging is restricted to a superficial region. Although inorganic nanoparticles such as quantum dots or upconverting nanoparticles possess bright fluorescence and good photostability, their heavy metal components would cause further toxicity concerns.
Unlike conventional organic fluorophores, luminogens with aggregation-induced emission (AIEgens) with propeller-shaped structures provide a superior choice for light-up fluorescence sensing. As isolated molecules, the rotor-containing AIEgens undergo low-frequency motions and dissipate exciton energy, leading to fast nonradiative decay of the excited states and weak emission. In the aggregated form, the radiative pathway is predominant for strong emission via the restriction of intramolecular rotation, vibration and motion. The AIEgen aggregates exhibit large absorptivity, robust luminosity, strong photobleaching resistance, no random blinking, and excellent biocompatibility. They have been widely applied for in vitro and in vivo biosensing and imaging, including specific biomolecular analysis (DNA, protein, enzyme, antigen, etc), micro-environment sensing (intracellular pH, membrane potential, viscosity, ROS, etc), real-time organelle or cellular imaging, highly sensitive pathogen detection, long-lasting drug delivery tracking and high-resolution biological process visualization (protein fibrillation, cell apoptosis, mitophagy, proliferation, etc).
Ben Zhong Tang is Stephen K. C. Cheong Professor of Science, Chair Professor of Chemistry, and Chair Professor of Chemical and Biological Engineering at The Hong Kong University of Science and Technology (HKUST). His research interests include macromolecular chemistry, materials science and biomedical theranostics. Tang received B.S. and Ph.D. degrees from South China University of Technology and Kyoto University, respectively. He conducted postdoctoral research at University of Toronto. He joined HKUST as an assistant professor in 1994 and was promoted to chair professor in 2008. He was elected to the Chinese Academy of Sciences and the Royal Society of Chemistry (RSC) in 2009 and 2013, respectively. Tang has published >1,400 papers. His publications have been cited >85000 times with an h-index of 135.
A novel 3D printing approach for structured microenvironments and defined cell behaviour
Hala ZREIQAT AM Professor Biomedical Engineering at the University of Sydney; a National Health and Medical Research Council Senior Research Fellow and is the Director of the Australian Research Centre for Innovative BioEngineering
Tissue is a complex heterogeneous structure. The fabrication of comparable structured synthetic tissues necessitates technologies able to recapitulate such heterogeneity. Towards this aim, we develop a novel 3D printing technology, flow lithography, for the fabrication of structured cellular microenvironments. Using this technique, we characterize the dependency of the independent parameters affecting the material properties and describe a strategy for fabricating substrates with independently defined biophysicochemical microproperties. We use flow lithography to fabricate cell microenvironments able to spatially define cell mechanosensing and to direct stem cell differentiation.
Hala Zreiqat AM is a Professor of Biomedical Engineering at the University of Sydney; a National Health and Medical Research Council Senior Research Fellow and is the Director of the Australian Research Centre for Innovative BioEngineering. Her research is on the development of novel engineered materials and 3D-printed platforms that mimic tissue structures, particularly in orthopaedic, dental, and maxillofacial applications. She has received national and international awards. She pioneers national and international technology development, and has received national and international awards, including the Order of Australia; the 2018 New South Wales Premier’s Woman of the Year; The King Abdullah II Order of Distinction of the Second Class - the highest civilian honour bestowed by the King of Jordan (2018); Eureka Prize winner for Innovative Use of Technology (2019); Fellow of the Australian Academy of Health and Medical Sciences (2019); Fellow of International Orthopaedic Research (FIOR); and University of Sydney Payne-Scott Professorial Distinction (2019).
Kristi Anseth Tisone Distinguished Professor Chemical and Biological Engineering and Head of Academic Leadership of the BioFrontiers Institute at the University of Colorado at Boulder, USA
Our group is interested in the development of macromolecular monomers that can be reacted into crosslinked polymer networks in the presence of living cells and tissues. From a fundamental perspective, we seek to decipher the critical extracellular matrix signals that are relevant for tissue development, regeneration, and disease and then design polymeric biomaterials that integrate these signals. From an applied perspective, we use this knowledge to design materials with precise properties that can promote tissue regeneration and wound healing in vivo. This talk will illustrate our recent efforts towards the synthesis of hydrogels for 4D cell culture and regenerative medicine, and demonstrate how one can dynamically control biochemical and biophysical properties through orthogonal, photochemical click reaction mechanisms. Some specific examples will include the design of hydrogels that promote musculoskeletal tissue regeneration, super-swelling matrices to visualize cell-matrix interactions with unprecedented resolution, and materials-directed growth of organoids from single stem cells. These efforts will then be placed in the context of designing precision biomaterials to address demands for patient specific products and treatments.
Kristi Anseth is the Tisone Distinguished Professor of Chemical and Biological Engineering and Head of Academic Leadership of the BioFrontiers Institute at the University of Colorado at Boulder, USA. Her research interests lie at the interface between biology and engineering where she designs new biomaterials for applications in drug delivery and regenerative medicine. Dr. Anseth is an elected member of the US National Academy of Engineering, National Academy of Medicine, National Academy of Sciences, National Academy of Inventors, and the American Academy of the Arts and Sciences. She is also an editor for Biomacromolecules and Progress in Materials Science.
Xavier Trepat ICREA Research Professor Institute for Bioengineering of Catalonia
Biological processes such as morphogenesis, tissue regeneration, and cancer invasion are driven by collective migration, division, and folding of epithelial tissues. Each of these functions is tightly regulated by mechanochemical networks and ultimately driven by physical forces. I will present maps of cell-cell and cell-extracellular matrix (ECM) forces during cell migration and division in a variety of epithelial models, from the expanding MDCK cluster to the regenerating zebrafish epicardium. These maps revealed that migration and division in growing tissues are jointly regulated. I will also present measurements of epithelial traction, tension, and luminal pressure in three-dimensional epithelia of controlled size and shape. By examining epithelial tension over time-scales of hours and for extreme nominal strains we establish a remarkable degree of tensional homeostasis mediated by superelastic behavior. Finally, I will present direct measurements of the forces that shape the intestinal organoid crypt.
Xavier Trepat was trained in Physics and Engineering at the University of Barcelona. In 2004 he obtained his PhD from the Medical School at the University of Barcelona. He then joined the Program in Molecular and Integrative Physiological Sciences at Harvard University as a postdoctoral researcher. In January 2011 he became an ICREA Research Professor at the Institute for Bioengineering of Catalonia (IBEC). Trepat’s research aims to understand how cells and tissues grow, move, invade and regenerate in a variety of processes in health and disease. To achieve this, he has developed technologies to measure cellular properties at the micro- and nanoscales. He has then applied these technologies to identify fundamental mechanisms in cell biology and biophysics.