Biofabrication of Organ-on-a-Chip Devices
A lecture presented by Dr. Milica Radisi. Professor, University of Toronto, Institute of Biomedical Engineering.
Biography
Dr. Milica Radisic is a Professor at the University of Toronto, Tier 1 Canada Research Chair in Organ-on-a-Chip Engineering and a Senior Scientist at the Toronto General Research Institute. She is also Director of the NSERC CREATE Training Program in Organ-on-a-Chip Engineering & Entrepreneurship and a co-lead for the Center for Research and Applications in Fluidic Technologies. She is a Fellow of the Royal Society of Canada-Academy of Science, Canadian Academy of Engineering, the American Institute for Medical & Biological Engineering, Tissue Engineering & Regenerative Medicine Society as well as Biomedical Engineering Society. She was a recipient of the MIT Technology Review Top 35 Under 35, Queen Elizabeth II Diamond Jubilee Medal, NSERC E.W.R Steacie Fellowship, YWCA Woman of Distinction Award, Killam Fellowship, Acta Biomaterialia Silver Medal, and Humboldt Research Award to name a few. Her research focuses on organ-on-a-chip engineering and development of new biomaterials that promote healing and attenuate scarring. She developed new methods to mature iPSC derived cardiac tissues using electrical stimulation. She is a co-founder of two companies TARA Biosystems (acquired by Valo Health), that uses human engineered heart tissues in drug development and safety testing, and Quthero that advances regenerative hydrogels.
Abstract
Studies of human disease and drug discovery traditionally depend on cell lines in two dimensional configurations and animal studies. These approaches suffer from the inability to capture the diversity of human genetics, cell-cell interaction and multi-faceted responses that occur in human tissues and organs. With the advances in human pluripotent stem cell biology, we are now able to generate essentially any cell type of the human body through reprogramming and directed differentiation. In recent years, the convergence of microfabrication and tissue engineering gave rise to organ-on-a-chip technologies, which offer an alternative to conventional preclinical models for drug screening and disease modelling. Organ-on-a-chip devices can replicate key aspects of human physiology crucial for the understanding of drug effects, improving preclinical safety and efficacy testing, without reproducing the entire human organ but just key sub structures. Here, I will we discuss how organ-on-a-chip technologies can recreate functions of organs, specifically focusing on technologies developed in the Radisic lab such as Biowire heart-on-a-chip, Angiochip for vascularization of heart and liver tissues, and hFIBER model of the kidney glomerulus. I will additionally focus on the use of 3D printing and biofabrication to enhance the throughput of organ-on-a-chip device production and provide new embodiments for cell cultivation on soft yet permeable and mechanically stable substrates. I will discuss extrusion 3D printing of thermoplastic elastomer composites that enabled us to increase the fabrication efficiency of Biowire heart-on-a-chip device by over 60,000%. I will also discuss a high throughput 3D printing approach via coaxial extrusion to fabricate perfusable elastomeric microtubes of unprecedently small inner diameter (350 to 550 mm) and wall thickness (40-60 mm) for vascularization of organ-on-a-chip devices. This approach afforded the fabrication of multiple biomimetic shapes resembling cochlea and kidney glomerulus and afforded facile, high-throughput generation of perfusable structures that can be seeded with endothelial cells for organ