Function Follows Form: Oriented Substrate Nanotopography Overrides Neurite-Repulsive Schwann Cell–Astrocyte Barrier Formation in an In Vitro Model of Glial Scarring

Nano Letters, vol. 23, pp. 6337–6346

Abstract

Schwann cell (SC) transplantation represents a promising therapeutic approach for traumatic spinal cord injury but is frustrated by barrier formation, preventing cell migration, and axonal regeneration at the interface between grafted SCs and reactive resident astrocytes (ACs). Although regenerating axons successfully extend into SC grafts, only a few cross the SC–AC interface to re-enter lesioned neuropil. To date, research has focused on identifying and modifying the molecular mechanisms underlying such scarring cell–cell interactions, while the influence of substrate topography remains largely unexplored. Using a recently modified cell confrontation assay to model SC–AC barrier formation in vitro, highly oriented poly(ε-caprolactone) nanofibers were observed to reduce AC reactivity, induce extensive oriented intermingling between SCs and ACs, and ultimately enable substantial neurite outgrowth from the SC compartment into the AC territory. It is anticipated that these findings will have important implications for the future design of biomaterial-based scaffolds for nervous tissue repair.

Authors 11

1. Pascal Achenbach corresponding Aachen Department of Neurology Institute of Neuropathology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Neurology, RWTH Aachen University Hospital, 52074 Aachen, Germany

   Institute of Neuropathology, RWTH Aachen University Hospital, 52074 Aachen, Germany

2. Laura Hillerbrand

   University of Würzburg · Universitätsklinikum Würzburg

   Affiliation as printed

   Department of Functional Materials in Medicine and Dentistry, University Hospital Würzburg, 97070 Würzburg, Germany

3. José L. Gerardo-Nava Aachen Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering DWI - Leibniz Institute for Interactive Materials

   DWI – Leibniz Institute for Interactive Materials · Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Advanced Materials for Biomedicine (AMB), Institute of Applied Medical Engineering (AME), RWTH Aachen University Hospital, 52074 Aachen, Germany

   DWI - Leibniz Institute for Interactive Materials, 52074 Aachen, Germany

4. Axel Dievernich Aachen FEG Textiltechnik Forschungs- und Entwicklungsgesellschaft mbH

   FEG Textiltechnik (Germany)

   Affiliation as printed

   FEG Textiltechnik Forschungs- und Entwicklungsgesellschaft mbH, 52070 Aachen, Germany

5. Dorothée Hodde Aachen Institute of Neuropathology

   Universitätsklinikum Aachen · Ludwig-Maximilians-Universität München · RWTH Aachen University

   Affiliation as printed

   Institute of Neuropathology, RWTH Aachen University Hospital, 52074 Aachen, Germany

   University Hospital, Ludwig Maximilian University of Munich, 81377 Munich, Germany

6. Antonio S. Sechi Aachen Department of Cell and Tumor Biology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Cell and Tumor Biology, RWTH Aachen University Hospital, 52074 Aachen, Germany

7. Paul D. Dalton

   University of Oregon

   Affiliation as printed

   Phil and Penny Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, Oregon 97403, United States

8. Andrij Pich Aachen DWI - Leibniz Institute for Interactive Materials Institute of Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI - Leibniz Institute for Interactive Materials, 52074 Aachen, Germany

   Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany

9. Joachim Weis Aachen Institute of Neuropathology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Neuropathology, RWTH Aachen University Hospital, 52074 Aachen, Germany

10. Haktan Altinova Aachen Department of Neurosurgery Institute of Neuropathology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Department of Neurosurgery, RWTH Aachen University Hospital, 52074 Aachen, Germany

    Institute of Neuropathology, RWTH Aachen University Hospital, 52074 Aachen, Germany

11. Gary Anthony Brook Aachen Institute of Neuropathology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute of Neuropathology, RWTH Aachen University Hospital, 52074 Aachen, Germany