title: Three-dimensional nanofibrous scaffolds incorporating immobilized BDNF promote proliferation and differentiation of cortical neural stem cells.
abstract: Attempts to repair the central nervous system damaged as a result of trauma or disease will depend on the ability to restore the appropriate neuronal connectivity. This will rely on establishing appropriate chemical and physical environments for supporting neural cells and their processes and in this regard, engineering of biomaterials is of increasing interest. It will be important to understand how cells behave on these biomaterials in vitro, prior to future in vivo application. We reveal that modification of 3-dimensional (3D) electrospun poly-epsilon-caprolactone (PCL) nanofiber scaffolds by fiber alignment and aminolysation is superior to classical 2-dimensional (2D) culture-ware in promoting in vitro proliferation and differentiation of cortical cells. Many studies have examined the importance of exogenous soluble factors to promote cell fate specification. Here, we demonstrate that tethering the neurotrophin, brain-derived neurotrophic factor (BDNF), onto modified nanofibers is superior to culturing in the presence of soluble BDNF. Functional immobilization of BDNF to polymer nanofibers enhances neural stem cell (NSC) proliferation and directs cell fate toward neuronal and oligodendrocyte specification, essential for neural tissue repair. These findings indicate that modified PCL nanofibrous 3D scaffolds are capable of supporting NSCs and their derivatives and may present a new avenue for encouraging neural repair in the future.
authors.affiliation: Florey Neuroscience Institutes and Centre for Neurosciences, University of Melbourne, Melbourne, Australia.
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Horne
authors.forename: David R
authors.initials: DR
authors.lastname: Nisbet
authors.forename: John S
authors.initials: JS
authors.lastname: Forsythe
authors.forename: Clare L
authors.initials: CL
authors.lastname: Parish
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D055767:Immobilized Proteins / Q000494:pharmacology; D051379:Mice; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011091:Polyesters / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D055767:Immobilized Proteins; D011091:Polyesters; C016240:polycaprolactone