Shaping living tissues using microfabricated structures

Abstract

In this paper, we present a technique for shaping the morphology of living Multi Cellular Tumour Spheroids (MCTS) by using micro-engineered structures. To that aim we created biocompatible, high aspect ratio, polydimethylsiloxane (PDMS) microstructures, that are compatible with the size of MCTS. We show that these microstructures can conform MCTS into pre-determined shapes by confining them, under cell culture conditions. This moulding of a living growing tissue by PDMS microstructures needs optimization of surface conditions, in order to favour the wetting of the mould by the cells, while preventing their attachment to the confining structures. An adequate treatment of PDMS with non-adhesive coating turned out to be mandatory for combining a successful shaping and a soft unmoulding of the engineered tissue. After unmoulding, the tissues are still viable and can be further cultured. Our work demonstrates that very sharp corners can be moulded on originally spherical aggregates of cells and that freestanding cell architectures of arbitrary shapes can be generated. This bio-moulding process can therefore be used for the investigation of the rheological properties of tissues as well as morphogenesis mechanisms by measuring the post-moulding evolution of the engineered shape.