title: Nanofibrous scaffolds releasing a small molecule BDNF-mimetic for the re-direction of endogenous neuroblast migration in the brain.
abstract: Brain tissue engineering has the potential to harness existing elements of neurogenesis within the adult brain to overcome a microenvironment that is otherwise inhibitory to regeneration, especially following severe tissue damage. This study investigates the ability of electrospun poly ε-caprolactone (PCL) to re-direct the migratory pathway of endogenous neuroblasts from the disrupted subventricular zone (SVZ). A small molecule non-peptide ligand (BDNF-mimetic) that mimicked the trophic properties of brain-derived neurotrophic factor (BDNF) was incorporated into electrospun PCL scaffolds to improve neuroblast survival and promote neuroblast migration towards the implant. PCL scaffolds were able to support neuroblast infiltration and migration along the implant tract. In the presence of the BDNF-mimetic, neuroblasts were able to migrate towards the implant via the parenchyma, and their persistence within the implants was prolonged. In addition, the BDNF-mimetic improved implant integration and increased local neuronal plasticity by increasing neurite sprouting at the tissue-implant interface. SMI32+ neurites were observed inside scaffolds at 21 days but not 8 days post implantation, indicating that at least some of the infiltrated neuroblasts had differentiated into neurons.
authors.affiliation: Department of Materials Engineering, Monash University, Clayton, VIC 3800, Australia; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Deniece
authors.initials: D
authors.lastname: Fon
authors.affiliation: Department of Materials Engineering, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Materials Engineering, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ercole
authors.affiliation: CSIRO Materials Science and Engineering, Clayton, VIC 3053, Australia.
authors.forename: Friederike
authors.initials: F
authors.lastname: Fehr
authors.affiliation: CSIRO Materials Science and Engineering, Clayton, VIC 3053, Australia.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marchesan
authors.affiliation: Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Myles R
authors.initials: MR
authors.lastname: Minter
authors.affiliation: Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Crack
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: d.finkelstein@florey.edu.au.
authors.forename: David I
authors.initials: DI
authors.lastname: Finkelstein
authors.affiliation: Department of Materials Engineering, Monash University, Clayton, VIC 3800, Australia. Electronic address: john.forsythe@monash.edu.
authors.forename: John S
authors.initials: JS
authors.lastname: Forsythe
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology; D040761:Biomimetic Materials / Q000494:pharmacology*; D001921:Brain / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology; D008297:Male; D017628:Microglia / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009479:Neuropeptides / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D011091:Polyesters; C016240:polycaprolactone
keywords: BDNF-mimetic; Brain repair; Neural tissue engineering; Neuroblast migration; PCL scaffold; Subventricular zone