Dynamic bioengineered hydrogels as scaffolds for advanced stem cell and organoid culture
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Biomaterials for 3D Cell Biology Prospective Article
Dynamic bioengineered hydrogels as scaffolds for advanced stem cell and organoid culture Laura C. Bahlmann†, Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario M5S3E1, Canada Ana Fokina†, Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario M5S 3E5, Canada Molly S. Shoichet, Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario M5S3E1, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario M5S 3E5, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada Address all correspondence to Molly S. Shoichet at [email protected] (Received 11 May 2017; accepted 10 August 2017)
Abstract Bioengineered hydrogels enable systematic variation of mechanical and biochemical properties, resulting in the identification of optimal in vitro three-dimensional culture conditions for individual cell types. As the scientific community attempts to mimic and study more complex biologic processes, hydrogel design has become multi-faceted. To mimic organ and tissue heterogeneity in terms of spatial arrangement and temporal changes, hydrogels with spatiotemporal control over mechanical and biochemical properties are needed. In this prospective article, we present studies that focus on the development of hydrogels with dynamic mechanical and biochemical properties, highlighting the discoveries made using these scaffolds.
Introduction Organoids, multi-cellular aggregates which recapitulate multiple aspects of a single organ, present promising models for in vitro organ development, disease modeling, and drug screening. During organoid formation, cells differentiate and selforganize according to the biochemical and mechanical cues encountered. Every organ in the human body has a very specific set of these cues that result in precise control over cell fate. To create organoids, which resemble the organ of specific interest, be it liver or heart, scientists must learn what these cues are and how to provide them in vitro in order to recapitulate the natural microenvironment. Matrigel is a naturally derived material that has been shown to promote organoid growth and selfassembly; however, its xenogeneic source and batch-to-batch variation, limit its use for in vivo applications and systematic studies of tumor and organ development.[1] Moreover, since Matrigel contains a variety of extracellular matrix (ECM) proteins, cytokines, and growth factors, it is difficult to determine which components are essential for a specific developmental event. Bioengineered hydrogels allow researchers to mimic specific in vivo conditions in a controlled manner, where biochemical and mechanical properties can be varied systematically and independently from each other. Recently, hydrogels have been used to in
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