Promoting neuronal outgrowth using ridged scaffolds coated with extracellular matrix proteins

Ahad M. Siddiqui, Rosa Brunner, Gregory M. Harris, Alan Lee Miller, Brian E. Waletzki, Ann M. Schmeichel, Jean E. Schwarzbauer, Jeffrey Schwartz, Michael J. Yaszemski, Anthony J. Windebank, Nicolas N. Madigan

Research output: Contribution to journalArticlepeer-review

Abstract

Spinal cord injury (SCI) results in cell death, demyelination, and axonal loss. The spinal cord has a limited ability to regenerate, and current clinical therapies for SCI are not effective in helping promote neurologic recovery. We have developed a novel scaffold biomaterial that is fabricated from the biodegradable hydrogel oligo(poly(ethylene glycol)fumarate) (OPF). We have previously shown that positively charged OPF scaffolds (OPF+) in an open spaced, multichannel design can be loaded with Schwann cells to support axonal generation and functional recovery following SCI. We have now developed a hybrid OPF+ biomaterial that increases the surface area available for cell attachment and that contains an aligned microarchitecture and extracellular matrix (ECM) proteins to better support axonal regeneration. OPF+ was fabricated as 0.08 mm thick sheets containing 100 µm high polymer ridges that self-assemble into a spiral shape when hydrated. Laminin, fibronectin, or collagen I coating promoted neuron attachment and axonal outgrowth on the scaffold surface. In addition, the ridges aligned axons in a longitudinal bipolar orientation. Decreasing the space between the ridges increased the number of cells and neurites aligned in the direction of the ridge. Schwann cells seeded on laminin coated OPF+ sheets aligned along the ridges over a 6-day period and could myelinate dorsal root ganglion neurons over 4 weeks. This novel scaffold design, with closer spaced ridges and Schwann cells, is a novel biomaterial construct to promote regeneration after SCI.

Original languageEnglish (US)
Article number479
JournalBiomedicines
Volume9
Issue number5
DOIs
StatePublished - May 2021

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

Keywords

  • Axonal regeneration
  • Cell attachment
  • Extracellular matrix
  • Neuronal outgrowth
  • Scaffolds
  • Schwann cells
  • Spinal cord

Fingerprint

Dive into the research topics of 'Promoting neuronal outgrowth using ridged scaffolds coated with extracellular matrix proteins'. Together they form a unique fingerprint.

Cite this