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.
Highlights
IntroductionThe spinal cord has a limited ability to regenerate after spinal cord injury (SCI), and available therapies are not efficacious in promoting the recovery of motor and sensory neurological function
We have previously demonstrated that oligo(poly(ethylene glycol)fumarate) (OPF)+ fabricated in a multichannel design with seven channels can enhance regeneration after Spinal cord injury (SCI) [4,7] in rats
We have shown that the OPF+ material can be modified by incorporating the anti-fibrotic drug rapamycin in PLGA microspheres [27]
Summary
The spinal cord has a limited ability to regenerate after spinal cord injury (SCI), and available therapies are not efficacious in promoting the recovery of motor and sensory neurological function. The failure to recover function may be due to secondary events that occur after the primary insult such as cell death, axonal loss, demyelination, cyst formation, and an increase in the inhibitory microenvironment [1]. Many therapies are currently under investigation for treating one or more of these secondary events using neuroprotective strategies and cell, regenerative, and rehabilitative therapies [1,2]. A single therapeutic strategy is unlikely to be effective in treating a disorder that is heterogeneous 4.0/).
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