Biomimetic dynamic mechanobiology: developing control strategies for self-organizing microengineered tissues

点击翻译按钮获取中文摘要

Nature of the work: The process by which we grow and differentiate from homogenous embryos into precisely-sculpted, functional tissues and organs is a manufacturing marvel that is far more precise, robust, and adaptive than current tissue engineering process control strategies. Mechanical forces are process variables that must play a central role in tissue formation during development, and in tissue disruption during disease; but the tools to measure, recreate, and manipulate these potent stimuli have lagged far behind the explosive growth of reductionist molecular biology techniques. The long-term goals of this research program are to leverage microfabrication, materials design, and stem cell tissue engineering to (1) understand the co-evolution of mechanics and biology as tissues develop and decay; and (2) exploit these insights to engineer biological process systems of value to society. Anticipated outcomes. Over the next five years, we will explore mechanical plasticity as a critical regulator of cell fate and function, and develop tools to measure and manipulate these parameters in native and engineered cultures. We anticipate developing fundamental strategies to understand the mechanical relationship between cells and their environment, with initial applications in organoid differentiation and control. Though broadly applicable to several problems in microscale tissue engineering for human health, we will then apply this paradigm in a focused effort to develop microengineered strategies to reduce the costs of sustainable materials development. Specifically, we will investigate the plastic-to-elastic transition driven by a colonizing fungal network in granular substrates, which has been proposed as a sustainable alternative material for many industries, but remains economically challenging to adopt broadly. This design cycle should hence provide creative and fundamentally-grounded approaches to biological engineering challenges, and we specifically envision the fundamental knowledge and experience gained through this interdisciplinary approach to impact the fundamental research, biomanufacturing, and agricultural industries. Furthermore, this fundamental knowledge will lay the preliminary groundwork to address critical healthcare challenges in drug screening, regenerative medicine, and diagnostics. Benefits to Canada. In addition to the scientific research outcomes described and the potential innovative applications to industry, this proposed work will train 3 doctoral, 3 masters, and 9 undergraduate researchers at the highly interdisciplinary interface between bioprocessing, mechanics, tissue engineering, and sustainable development. Given the pressing need for creative and sustainable approaches to manufacturing, the proposed training environment and program will position trainees ahead of the curve to invent, develop, and deliver creative strategies to effect positive change in a future-focused society.