The design of innovative tools for generating physiologically relevant three-dimensional (3D) in vitro models has been recently recognized as a fundamental step to study cell responses and long-term tissue functionalities thanks to its ability to recapitulate the complexity and the dimensional scale of the cellular microenvironment, while directly integrating high-throughput and automatic screening capabilities.This chapter addresses the development of a poly(dimethylsiloxane)-based microfluidic platform to (1) generate and culture 3D cellular microaggregates under continuous flow perfusion while (2) conditioning them with different combinations/concentrations of soluble factors (i.e., growth factors, morphogens or drug molecules), in a high-throughput fashion. The proposed microfluidic system thus represents a promising tool for establishing innovative high-throughput models for drug screening, investigation of tissues morphogenesis, and optimization of tissue engineering protocols.
Keywords: High-throughput screening; Mesenchymal stem cells; Microfluidics; Perfused micromasses; Soft-lithography.