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Article

Promoting Neuronal Outgrowth Using Ridged Scaffolds Coated with Extracellular Matrix Proteins

1
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
2
Program in Human Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
3
Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA
4
Department of Orthopaedic Surgery, Mayo Clinic, Rochester, MN 55905, USA
5
Department of Chemistry, Princeton University, Princeton, NJ 08544, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Petr Krupa
Biomedicines 2021, 9(5), 479; https://doi.org/10.3390/biomedicines9050479
Received: 26 March 2021 / Revised: 22 April 2021 / Accepted: 23 April 2021 / Published: 27 April 2021
(This article belongs to the Special Issue Advancements in the Treatment of Spinal Cord Injury)
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. View Full-Text
Keywords: neuronal outgrowth; cell attachment; Schwann cells; extracellular matrix; scaffolds; spinal cord; axonal regeneration neuronal outgrowth; cell attachment; Schwann cells; extracellular matrix; scaffolds; spinal cord; axonal regeneration
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MDPI and ACS Style

Siddiqui, A.M.; Brunner, R.; Harris, G.M.; Miller, A.L., II; Waletzki, B.E.; Schmeichel, A.M.; Schwarzbauer, J.E.; Schwartz, J.; Yaszemski, M.J.; Windebank, A.J.; Madigan, N.N. Promoting Neuronal Outgrowth Using Ridged Scaffolds Coated with Extracellular Matrix Proteins. Biomedicines 2021, 9, 479. https://doi.org/10.3390/biomedicines9050479

AMA Style

Siddiqui AM, Brunner R, Harris GM, Miller AL II, Waletzki BE, Schmeichel AM, Schwarzbauer JE, Schwartz J, Yaszemski MJ, Windebank AJ, Madigan NN. Promoting Neuronal Outgrowth Using Ridged Scaffolds Coated with Extracellular Matrix Proteins. Biomedicines. 2021; 9(5):479. https://doi.org/10.3390/biomedicines9050479

Chicago/Turabian Style

Siddiqui, Ahad M., Rosa Brunner, Gregory M. Harris, Alan L. Miller II, Brian E. Waletzki, Ann M. Schmeichel, Jean E. Schwarzbauer, Jeffrey Schwartz, Michael J. Yaszemski, Anthony J. Windebank, and Nicolas N. Madigan. 2021. "Promoting Neuronal Outgrowth Using Ridged Scaffolds Coated with Extracellular Matrix Proteins" Biomedicines 9, no. 5: 479. https://doi.org/10.3390/biomedicines9050479

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