Co-Delivery of Docosahexaenoic Acid and Brain-Derived Neurotropic Factor from Electrospun Aligned Core–Shell Fibrous Membranes in Treatment of Spinal Cord Injury

Abstract

To restore lost functions while repairing the neuronal structure after spinal cord injury (SCI), pharmacological interventions with multiple therapeutic agents will be a more effective modality given the complex pathophysiology of acute SCI. Toward this end, we prepared electrospun membranes containing aligned core–shell fibers with a polylactic acid (PLA) shell, and docosahexaenoic acid (DHA) or a brain-derived neurotropic factor (BDNF) in the core. The controlled release of both pro-regenerative agents is expected to provide combinatory treatment efficacy for effective neurogenesis, while aligned fiber topography is expected to guide directional neurite extension. The in vitro release study indicates that both DHA and BDNF could be released continuously from the electrospun membrane for up to 50 days, while aligned microfibers guide the neurite extension of primary cortical neurons along the fiber axis. Furthermore, the PLA/DHA/BDNF core–shell fibrous membrane (CSFM) provides a significantly higher neurite outgrowth length from the neuron cells than the PLA/DHA CSFM. This is supported by the upregulation of genes associated with neuroprotection and neuroplasticity from RT-PCR analysis. From an in vivo study by implanting a drug-loaded CSFM into the injury site of a rat suffering from SCI with a cervical hemisection, the co-delivery of DHA and BDNF from a PLA/DHA/BDNF CSFM could significantly improve neurological function recovery from behavioral assessment, as well as provide neuroprotection and promote neuroplasticity changes in recovered neuronal tissue from histological analysis.

Keywords

• spinal cord injury
• docosahexaenoic acid
• brain-derived neurotrophic factor
• electrospinning
• regenerative medicine