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Poster #10
Squish tissue culture: A hydrogel platform for on-demand application of 3D forces to engineered tissues
Camille Cassel de Camps1, Stephanie Mok2, Christopher Moraes1,2,3
1Department of Biomedical Engineering, McGill University, Montréal
2Department of Chemical Engineering, McGill University, Montréal
3Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montréal
Morphogenesis, the complex shape-shifting process by which tissues and organisms take shape, necessarily involves mechanical forces acting in 3D, but tools to apply 3D forces to 3D tissues in a tissue culture setting are lacking. Here, we showcase a temperature-actuated hydrogel platform to apply directionally-defined forces in 3D to engineered tissues in culture. The hydrogel devices contain micro-cavities to hold the cultured tissue, and were cast using 3D-printed molds with poly(N-isopropylacrylamide) (NIPAM), a thermoresponsive polymer which contracts above ~32°C; incubation triggers the devices to shrink, applying compressive forces on the tissue. Spheroids and organoids were transferred into NIPAM devices with cavities of various shapes and dimensions designed to exert spatially-defined forces on the growing tissues. Gross morphology of spheroids/organoids was monitored over time to observe their responses to the applied forces. Micro-cavities shrank significantly upon incubation. In circular cavities, compression of spheroids by ~50% was achieved within 4 hours, and was sustained for 24 hours. Rectangular cavities were used to apply non-uniform compression. Donut-shaped cavities were tested to mimic bending forces during morphogenesis, reminiscent of the tubes formed during development of many organs. Organoids adopted the desired bent shape, and continued to grow over 7 days. The platform developed in this work achieves application of mechanical forces in 3D on cultured tissues, providing a new tool to the field. This platform enables observation of tissue response to spatially-defined forces, and will facilitate exploration of the mechanical forces involved in morphogenesis to further our understanding of this complex and difficult-to-study process.