1. Local Release of Paclitaxel from Aligned, Electrospun Microfibers Promotes Axonal Extension
- Author
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Andres Hurtado, Ian Reucroft, Russell Martin, Hai-Quan Mao, and Jose Roman
- Subjects
0301 basic medicine ,Materials science ,Paclitaxel ,Polymers ,Neurogenesis ,Polyesters ,Biomedical Engineering ,Pharmaceutical Science ,02 engineering and technology ,Inhibitory postsynaptic potential ,Article ,Rats, Sprague-Dawley ,Biomaterials ,03 medical and health sciences ,chemistry.chemical_compound ,Dorsal root ganglion ,Laminin ,Ganglia, Spinal ,Neurites ,medicine ,Animals ,Spinal cord injury ,Cells, Cultured ,Spinal Cord Injuries ,Aggrecan ,Neurons ,Tissue Scaffolds ,biology ,Regeneration (biology) ,technology, industry, and agriculture ,021001 nanoscience & nanotechnology ,Spinal cord ,medicine.disease ,Axons ,Nerve Regeneration ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Biophysics ,biology.protein ,0210 nano-technology ,Biomedical engineering - Abstract
Traumatic spinal cord injuries ultimately result in an inhibitory environment that prevents axonal regeneration from occurring. A low concentration administration of paclitaxel has been previously shown to promote axonal extension and attenuate the upregulation of inhibitory molecules after a spinal cord injury. In this study we incorporated paclitaxel into electrospun poly(l-lactic acid) (PLA) microfibers and established that a local release of paclitaxel from aligned, electrospun microfibers promotes neurite extension in a growth-conducive and inhibitory environment. Isolated dorsal root ganglion cells were cultured for five days directly on tissue culture polystyrene surface, PLA film, random, or aligned electrospun PLA microfibers (1.44 ± 0.03 µm) with paclitaxel incorporated at various concentrations (0 – 5.0% w/w in reference to fiber weight). To determine the effect of a local release of paclitaxel, paclitaxel-loaded microfibers were placed in CellCrown™ inserts above cultured neurons. Average neurite extension rate was quantified for each sample. A local release of paclitaxel maintained neuronal survival and neurite extension in a concentration-dependent manner when coupled with aligned microfibers when cultured on laminin or an inhibitory surface of aggrecan. Our findings provide a targeted approach to improve axonal extension across the inhibitory environment present after a traumatic injury in the spinal cord.
- Published
- 2016