title: Glial progenitor cell migration promotes CNS axon growth on functionalized electroconducting microfibers.
abstract: Electroactive systems that promote directional axonal growth and migration of glial progenitor cells (GPC) are needed for the treatment of neurological injuries. We report the functionalization of electroconducting microfibers with multiple biomolecules that synergistically stimulate the proliferation and migration of GPC, which in turn induce axonal elongation from embryonic cerebral cortex neurons. PEDOT doped with poly[(4-styrenesulfonic acid)-co-(maleic acid)] was synthesized on carbon microfibers and used for covalent attachment of molecules to the electroactive surface. The molecular complexes that promoted GPC proliferation and migration, followed by axonal extension, were composed of polylysine, heparin, basic fibroblast growth factor (bFGF), and matricellular proteins; the combination of bFGF with vitronectin or fibronectin being indispensable for sustained glial and axonal growth. The rate of glial-induced axonal elongation was about threefold that of axons growing directly on microfibers functionalized with polylysine alone. Electrical stimuli applied through the microfibers released bFGF and fibronectin from the polymer surface, consequently reducing GPC proliferation and promoting their differentiation into astrocytes, without causing cell detachment or toxicity. These results suggest that functionalized electroactive microfibers may provide a multifunctional tool for controlling neuron-glia interactions and enhancing neural repair.
  
  
  CONCLUSIONS
  We report a multiple surface functionalization strategy for electroconducting microfibers (MFs), in order to promote proliferation and guided migration of glial precursor cells (GPC) and consequently create a permissive substrate for elongation of central nervous system (CNS) axons. GPC divided and migrated extensively on the functionalized MFs, leading to fast elongation of embryonic cerebral cortex axons. The application of electric pulses thorough the MFs controlled glial cell division and differentiation. The functionalized MFs provide an advanced tool for neural tissue engineering and for controlling neuron-glial interactions. CNS axonal growth associated to migratory glial precursors, together with the possibility of directing glial differentiation by electrical stimuli applied through the MFs, open a new research avenue to explore for CNS repair.
authors.affiliation: Neural Repair and Biomaterials Laboratory, Hospital Nacional de Parapléjicos (SESCAM), Finca La Peraleda s/n, 45071 Toledo, Spain. Electronic address: jcollazos@sescam.org.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Collazos-Castro
authors.affiliation: Neural Repair and Biomaterials Laboratory, Hospital Nacional de Parapléjicos (SESCAM), Finca La Peraleda s/n, 45071 Toledo, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: García-Rama
authors.affiliation: Neural Repair and Biomaterials Laboratory, Hospital Nacional de Parapléjicos (SESCAM), Finca La Peraleda s/n, 45071 Toledo, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Alves-Sampaio
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002244:Carbon / Q000494:pharmacology*; D000077482:Carbon Fiber; D002417:Cattle; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002490:Central Nervous System / Q000166:cytology; D004553:Electric Conductivity; D004558:Electric Stimulation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005353:Fibronectins / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects; D056951:Photoelectron Spectroscopy; D011108:Polymers / Q000494:pharmacology; D011137:Polystyrenes / Q000494:pharmacology; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D000077482:Carbon Fiber; D005353:Fibronectins; D011108:Polymers; D011137:Polystyrenes; C121383:poly(3,4-ethylene dioxythiophene); D016222:Fibroblast Growth Factor 2; C003321:polystyrene sulfonic acid; D002244:Carbon; D006493:Heparin
keywords: Axonal; Conducting polymers; Fibronectin; Glial; Microfibers; bFGF