Development of a glial cell-derived neurotrophic factor-releasing artificial dura for neural tissue engineering applications

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dc.contributor.authorMohtaram, N.K.
dc.contributor.authorKo, J.
dc.contributor.authorAgbay, A.
dc.contributor.authorRattray, D.
dc.contributor.authorNeill, P.O.
dc.contributor.authorRajwani, A.
dc.contributor.authorVasandani, R.
dc.contributor.authorThu, H.L.
dc.contributor.authorJun, M.B.G.
dc.contributor.authorWillerth, Stephanie
dc.date.accessioned2017-08-29T16:35:28Z
dc.date.available2017-08-29T16:35:28Z
dc.date.copyright2015en_US
dc.date.issued2015
dc.description.abstractEncapsulated electrospun nanofibers can serve as an artificial dura mater, the membrane that surrounds the brain and spinal cord, due to their desirable drug delivery properties. Such nanofiber scaffolds can be used to deliver drugs such as glial cell-derived neurotrophic factor (GDNF). GDNF promotes the survival of both dopaminergic and motor neurons, making it an important target for treatment of central nervous system injuries and disorders. This work focuses on designing a novel class of encapsulated poly(ε-caprolactone) (PCL) nanofiber scaffolds with different topographies (random and aligned) that generate controlled release of GDNF to potentially serve as a suitable substitute for the dura mater during neurosurgical procedures. Random and aligned scaffolds fabricated using solution electrospinning were characterized for their physical properties and their ability to release GDNF over one month. GDNF bioactivity was confirmed using a PC12 cell assay with the highest concentrations of released GDNF (∼341 ng mL−1 GDNF) inducing the highest levels of neurite extension (∼556 μm). To test the cytocompatibility of aligned GDNF encapsulated PCL nanofibers, we successfully seeded neural progenitors derived from human induced pluripotent stem cells (hiPSCs) onto the scaffolds where they survived and differentiated into neurons. Overall, this research demonstrates the potential of such substrates to act as artificial dura while delivering bioactive GDNF in a controlled fashion. These scaffolds also support the culture and differentiation of hiPSC-derived neural progenitors, suggesting their biocompatibility with the cells of the central nervous system.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThe authors would like to acknowledge the funding support from the Natural Sciences and Engineering Research Council’s Discovery Grant program, Canada Research Chair program and the Rick Hansen Foundation. The authors would also like to acknowledge the Advanced Microscopy Facility at the University of Victoria and Mr Nathan Bodie one of our lab volunteers who helped us with neurite outgrowth data analysis. The corresponding author acknowledges a previously held an Engage Grant with MedGenesis Therapeutix, who supported this project through donation of GDNF.en_US
dc.identifier.citationMohtaram, N.K., Ko, J. Agbay, A., Rattray, D., Neill, P.O., Rajwani, A., ...Willerth, S.M. (2015). Development of a glial cell-derived neurotrophic factor-releasing artificial dura for neural tissue engineering applications. Journal of Materials Chemistry B, 40(3), 7974-7985.en_US
dc.identifier.urihttp://dx.doi.org/10.1039/c5tb00871a
dc.identifier.urihttp://hdl.handle.net/1828/8484
dc.language.isoenen_US
dc.publisherJournals of Materials Chemistry Ben_US
dc.rightsAttribution 2.5 Canada*
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/ca/*
dc.subjectInstitute for Integrated Energy Systems (IESVic)
dc.subject.departmentDepartment of Mechanical Engineering
dc.subject.departmentSchool of Medical Sciences
dc.titleDevelopment of a glial cell-derived neurotrophic factor-releasing artificial dura for neural tissue engineering applicationsen_US
dc.typeArticleen_US

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