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 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.

Removal of retained electrospinning solvent prolongs drug release from electrospun PLLA fibers

“…In closing, it is important to compare findings presented here to other studies also releasing drug from electrospun fibers. While other studies report prolonged drug release from electrospun fibers,[17,20,27] those findings, along with results presented in this manuscript, are specific to the drug/polymer/solvent system that is being studied. For drug/polymer/solvent systems that inherently release drug in a linear fashion, these treatment methods are not necessary to prolong drug release.…”

“…By incorporating a drug within the polymer matrix of electrospun fibers, these scaffolds can provide physical cues that facilitate fast tissue regeneration while also delivering drugs to an injury site. Different approaches can modify the rate of drug release, including changing the amount of drug loaded into fibers,[13,17,18] altering fiber diameter,[19,20] selecting different polymers or utilizing different polymer concentrations,[13,18,19] or selecting specific solvents[19] to name a few. These fiber modifications are necessary since electrospun fibers frequently release drugs in a burst fashion within hours or days.…”

“…[13,17–19,21] A study by Kenawy and colleagues shows an abbreviated release of tetracycline HCl from electrospun PLLA fibers occurring instantaneously upon submersion in release buffer. [18] In contrast, Roman et al show prolonged release of paclitaxel from electrospun PLLA fibers that lasted for 84 days.…”

“…[18] In contrast, Roman et al show prolonged release of paclitaxel from electrospun PLLA fibers that lasted for 84 days. [17] A study by Zeng and colleagues discusses the effects of drug solubility and compatibility in a drug/polymer/solvent system which potentially explains the drastic differences in release kinetics observed from these various fiber scaffolds. This study showed that selecting a drug that is more compatible within a drug/polymer/solvent system will result in better encapsulation of drug within fibers and thus prolong the drug release from fibers.…”

Control of cell growth on 3D‐printed cell culture platforms for tissue engineering

“…In clinics, autograft, allograft, and xenograft are the conventional therapies used to repair skin defects . For skin tissue regeneration, suitable biological cell culture platforms able to guide fibroblasts growth are essential to promote effective wound healing …”