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Meso-scale multi-material fabrication of a Synthetic ECM Mimic for In vivo-like Peripheral Nerve Regeneration

Paul Wieringa, Ana Rita Gonçalves de Pinho, Roman Truckenmüller, Silvestro Micera, Richard van Wezel, Lorenzo Moroni
doi: https://doi.org/10.1101/842906
Paul Wieringa
1Complex Tissue Regeneration Department, MERLN Institute for Technology Inspired Regenerative Medicine Maastricht University, Maastricht, The Netherlands
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Ana Rita Gonçalves de Pinho
2FEUP, University of Porto, Port, Portugal
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Roman Truckenmüller
1Complex Tissue Regeneration Department, MERLN Institute for Technology Inspired Regenerative Medicine Maastricht University, Maastricht, The Netherlands
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Silvestro Micera
3BioRobotics Institute – Scuola Superiore Sant’Anna, Pisa, Italy
4Translational Neural Engineering Laboratory, Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
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Richard van Wezel
5Department of Biomedical Signals and Systems, MIRA, Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands
6Biophysics, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
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Lorenzo Moroni
1Complex Tissue Regeneration Department, MERLN Institute for Technology Inspired Regenerative Medicine Maastricht University, Maastricht, The Netherlands
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  • For correspondence: l.moroni@maastrichtuniversity.nl
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Abstract

A growing focus and continuing challenge for biological sciences is creating representative in vitro environments to study and influence cell behavior. Here, we describe the synthetic recreation of the highly ordered extracellular matrix (ECM) of the peripheral nervous system (PNS) in terms of structure and scale, providing a versatile 3D culturing platform that achieves some of the highest in vitro neurite growth rates so far reported. By combining electrospinning technology with a unique multi-material processing sequence that harnesses intrinsic material properties, a hydrogel construct is realized that incorporates oriented 6 μm-diameter microchannels decorated with topographical nanofibers. We show that this mimics the native PNS ECM architecture and promotes extensive growth from primary neurons; through controlled variation in design, we show that the open lumens of the microchannels directing rapid axon invasion of the hydrogel while the nanofibers provide essential cues for cell adhesion and topographical guidance. Furthermore, these microstructural and nanofibrillar elements enabled a typically bioinert hydrogel (PEGDA) to achieve similar neurite extension when compared to a biocompatible collagen hydrogel, with PEGDA-based devices approaching neurite growth rates similar to what is observed in vivo. Through the accessible fabrication approach developed here, multi-material scaffolds were designed with cell-relevant architectures ranging from meso-to nanoscale and shown to support nerve growth to mimic PNS regeneration, with potential for regenerative medicine and neural engineering applications.

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Posted November 15, 2019.
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Meso-scale multi-material fabrication of a Synthetic ECM Mimic for In vivo-like Peripheral Nerve Regeneration
Paul Wieringa, Ana Rita Gonçalves de Pinho, Roman Truckenmüller, Silvestro Micera, Richard van Wezel, Lorenzo Moroni
bioRxiv 842906; doi: https://doi.org/10.1101/842906
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Meso-scale multi-material fabrication of a Synthetic ECM Mimic for In vivo-like Peripheral Nerve Regeneration
Paul Wieringa, Ana Rita Gonçalves de Pinho, Roman Truckenmüller, Silvestro Micera, Richard van Wezel, Lorenzo Moroni
bioRxiv 842906; doi: https://doi.org/10.1101/842906

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