Profile and Department: Professor, Mechanical and Industrial Engineering, University of Toronto
Lab: Simmons Lab
Tissue engineering is a promising approach for the replacement and regeneration of damaged or diseased tissues and organs. Typical tissue engineering strategies seek to replicate components of the natural cellular microenvironment, including the extracellular matrix and soluble proteins. In the case of load-bearing tissues, mechanical stimulation is likely also required to engineer functional tissues. By providing specific complementary cues, the phenotype of host or transplanted cells can be regulated to guide tissue and organ regeneration. A critical step to defining design criteria for the next generation of functional tissue engineering systems is to determine how multiple exogenous cues integrate intracellularly to regulate cell function. Using a variety of cell culture models and in vivo experimentation, we are systematically and quantitatively investigating the integrated response of cells to combinations of relevant mechanobiological stimuli. The focus of our work is skeletal tissue engineering using mesenchymal stem cells (MSCs). MSCs have the ability to differentiate to several musculoskeletal cell types, and therefore are a promising autologous source for cell-based skeletal regeneration. We have identified several regulators of MSC osteogenic and chondrogenic differentiation of relevance to skeletal tissue engineering, including matrix-mediated signals, osteogenic growth factors, and mechanical stimuli. We are currently extending this work to determine relationships between multiple mechanobiological cues and the integrated response of MSCs. Our goal is to identify combinations of stimuli that guide cell function predictably and optimally, and in collaboration with biomaterial scientists apply these design criteria to develop novel ‘mechanoactive’ tissue engineering systems, bioreactors, and ex vivo growth protocols for functional skeletal tissue engineering.