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Biomaterials. 2019 Dec;225:119537. doi: 10.1016/j.biomaterials.2019.119537. Epub 2019 Oct 8.

A customizable microfluidic platform for medium-throughput modeling of neuromuscular circuits.

Author information

1
Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstr. 105, 01307, Dresden, Germany.
2
Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47/49, 01307, Dresden, Germany; Max Planck Institute for the Science of Light, Max-Planck-Zentrum für Physik und, Medizin, Staudtstr. 2, 91058, Erlangen, Germany.
3
Leibniz-Institut für Polymerforschung Dresden, Max Bergmann Center of Biomaterials, Hohe Straße 6, 01069, Dresden, Germany.
4
Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstr. 105, 01307, Dresden, Germany; Paul-Flechsig-Institut für Hirnforschung, Universität Leipzig, Liebigstraße 19, 04103, Leipzig, Germany.
5
Department of Microbiology, Immunology and Molecular Genetics, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Biology, University of California, Los Angeles, Biomedical Sciences Research Building, 615 Charles E. Young Drive, South, Los Angeles, CA, 90095, USA.
6
Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstr. 105, 01307, Dresden, Germany. Electronic address: jared.sterneckert@tu-dresden.de.

Abstract

Neuromuscular circuits (NMCs) are vital for voluntary movement, and effective models of NMCs are needed to understand the pathogenesis of, as well as to identify effective treatments for, multiple diseases, including Duchenne's muscular dystrophy and amyotrophic lateral sclerosis. Microfluidics are ideal for recapitulating the central and peripheral compartments of NMCs, but myotubes often detach before functional NMCs are formed. In addition, microfluidic systems are often limited to a single experimental unit, which significantly limits their application in disease modeling and drug discovery. Here, we developed a microfluidic platform (MFP) containing over 100 experimental units, making it suitable for medium-throughput applications. To overcome detachment, we incorporated a reactive polymer surface allowing customization of the environment to culture different cell types. Using this approach, we identified conditions that enable long-term co-culture of human motor neurons and myotubes differentiated from human induced pluripotent stem cells inside our MFP. Optogenetics demonstrated the formation of functional NMCs. Furthermore, we developed a novel application of the rabies tracing assay to efficiently identify NMCs in our MFP. Therefore, our MFP enables large-scale generation and quantification of functional NMCs for disease modeling and pharmacological drug targeting.

KEYWORDS:

Microfluidics; Motor unit; Neuromuscular circuit; Rabies viral tracing; Skeletal muscle; poly(ethylene-alt-maleic anhydride)

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