PT  - JOURNAL ARTICLE
AU  - Ahad M. Siddiqui
AU  - Rosa Brunner
AU  - Gregory M. Harris
AU  - Alan.L. Miller II
AU  - Brian E. Waletzki
AU  - Jean E. Schwarzbauer
AU  - Jeffrey Schwartz
AU  - Michael J. Yaszemski
AU  - Anthony J. Windebank
AU  - Nicolas N. Madigan
TI  - Promoting neuronal outgrowth using ridged scaffolds coated with extracellular matrix proteins
AID  - 10.1101/788539
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 788539
4099  - http://biorxiv.org/content/early/2019/10/01/788539.short
4100  - http://biorxiv.org/content/early/2019/10/01/788539.full
AB  - 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-assembles 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. The OPF+ sheets support axonal regeneration when implanted into the transected spinal cord. This novel scaffold design, with closer spaced ridges and Schwann cells is a novel biomaterial construct to promote regeneration after SCI.