A hybrid nanofiber matrix to control the survival and maturation of brain neurons

Shantanu Sur, Eugene T. Pashuck, Mustafa O. Guler, Masao Ito, Samuel I. Stupp, Thomas Launey*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Scaffold design plays a crucial role in developing graft-based regenerative strategies, especially when intended to be used in a highly ordered nerve tissue. Here we describe a hybrid matrix approach, which combines the structural properties of collagen (type I) with the epitope-presenting ability of peptide amphiphile (PA) nanofibers. Self-assembly of PA and collagen molecules results in a nanofibrous scaffold with homogeneous fiber diameter of 20-30 nm, where the number of laminin epitopes IKVAV and YIGSR can be varied by changing the PA concentrations over a broad range of 0.125-2 mg/ml. Granule cells (GC) and Purkinje cells (PC), two major neuronal subtypes of cerebellar cortex, demonstrate distinct response to this change of epitope concentration. On IKVAV hybrid constructs, GC density increases three-fold compared with the control collagen substrate at a PA concentration of ≥0.25 mg/ml, while PC density reaches a maximum (five-fold vs. control) at 0.25 mg/ml of PA and rapidly decreases at higher PA concentrations. In addition, adjustment of the epitope number allowed us to achieve fine control over PC dendrite and axon growth. Due to the ability to modulate neuron survival and maturation by easy manipulation of epitope density, our design offers a versatile test bed to study the extracellular matrix (ECM) contribution in neuron development and the design of optimal neuronal scaffold biomaterials.

Original languageEnglish (US)
Pages (from-to)545-555
Number of pages11
JournalBiomaterials
Volume33
Issue number2
DOIs
StatePublished - Jan 2012

Funding

This work was funded by the National Institutes of Health (NIH)/NIBIB Award No. 5R01EB003806-04 and RIKEN BSI intramural funding. AFM imaging was conducted at the Northwestern Nanoscale Integrated Fabrication, Testing, and Instrumentation Facility (NIFTI), TEM was conducted at the Northwestern Cell Imaging Facility, and cryogenic TEM was conducted at the Northwestern Biological Imaging Facility (BIF). SEM was performed by the Support Unit for Biomaterials Analysis in RIKEN BSI Research Ressources Center. The authors gratefully acknowledge the technical assistance provided by Yumiko Motoyama, Krista Niece, Megan Greenfield, Reiko Nakatomi and Christina Newcomb for cell culture, PA synthesis, rheology, SEM and TEM respectively.

Keywords

  • Brain
  • Collagen
  • Laminin
  • Nerve tissue engineering
  • Peptide amphiphile
  • Self assembly

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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