title: Local Release of Paclitaxel from Aligned, Electrospun Microfibers Promotes Axonal Extension.
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, paclitaxel is incorporated into electrospun poly(l-lactic acid) (PLA) microfibers, and it is 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 are cultured for 5 d 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 are placed in CellCrown inserts above cultured neurons. Average neurite extension rate is quantified for each sample. A local release of paclitaxel maintains 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. The findings provide a targeted approach to improve axonal extension across the inhibitory environment present after a traumatic injury in the spinal cord.
authors: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD, 21205, USA.|Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD, 21231, USA.|Institute for NanoBioTechnology, Johns Hopkins University, 3400 N Charles St, 100 Croft Hall, Baltimore, MD, 21218, USA.
authors: Jose A
authors: JA
authors: Roman
authors: Institute for NanoBioTechnology, Johns Hopkins University, 3400 N Charles St, 100 Croft Hall, Baltimore, MD, 21218, USA.
authors: Ian
authors: I
authors: Reucroft
authors: Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD, 21231, USA.|Institute for NanoBioTechnology, Johns Hopkins University, 3400 N Charles St, 100 Croft Hall, Baltimore, MD, 21218, USA.|Department of Materials Science and Engineering, Johns Hopkins University, 3400 N Charles St, Maryland Hall 206, Baltimore, MD, 21218, USA.
authors: Russell A
authors: RA
authors: Martin
authors: Department of Neurology, Johns Hopkins University School of Medicine, 1800 Orleans St, Baltimore, MD, 21287, USA.
authors: Andres
authors: A
authors: Hurtado
authors: Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD, 21231, USA. hmao@jhu.edu.|Institute for NanoBioTechnology, Johns Hopkins University, 3400 N Charles St, 100 Croft Hall, Baltimore, MD, 21218, USA. hmao@jhu.edu.|Department of Materials Science and Engineering, Johns Hopkins University, 3400 N Charles St, Maryland Hall 206, Baltimore, MD, 21218, USA. hmao@jhu.edu.
authors: Hai-Quan
authors: HQ
authors: Mao
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects*; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D016501:Neurites / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D011091:Polyesters; D011108:Polymers; C033616:poly(lactide); D017239:Paclitaxel
keywords: aligned microfibers; axonal extension; electrospinning; paclitaxel; poly(lactic acid)