title: Optimizing interfacial features to regulate neural progenitor cells using polyelectrolyte multilayers and brain derived neurotrophic factor.
abstract: The development of biomaterials with controllable interfacial features which have the capability to instruct cellular behavior are required to produce functional scaffolds for the treatment of spinal cord injury (SCI). Here, poly-ɛ-caprolactone surfaces were biofunctionalized via layer-by-layer (LbL) deposition. The polyelectrolytes employed in this LbL technique were heparin and poly-L-lysine (PLL), the latter being chosen to improve cell adhesion and the subsequent cellular function of in vitrocultured neural progenitor cells. Material characterization results confirmed the deposition of well structured multilayers. Cell culture studies revealed significant differences in the cellular response to these adhesive/nonadhesive (PLL/heparin) polyelectrolyte multilayer (PEM)surfaces, with neurite outgrowth being significantly promoted on the PLL terminating layers. In addition, brain derived neurotrophic factor (BDNF) was adsorbed onto the LbL surfaces. This combined chemical and biological effect was then characterized in terms of neurite length along with the full length/truncated isoform 1 tyrosine kinase receptor (TrkB-FL/TrkB-T1) and growth associated protein-43 mRNA levels. Here, the authors report the differential effect of adsorbed and soluble BDNF of different concentrations. Adsorbed BDNF promoted neurite outgrowth and led to elevated, sustained TrkB mRNA levels. These findings highlight the potential of PEM biofunctionalized surfaces with integrated chemical and neurotrophin supportive cues to overcome SCI inhibitory environments and to promote regeneration.
authors.affiliation: Department of Materials Engineering and Monash Immunology and Stem Cell Laboratories, Monash University, VIC, Australia.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhou
authors.forename: Gui Zhi
authors.initials: GZ
authors.lastname: Sun
authors.forename: Claude C
authors.initials: CC
authors.lastname: Bernard
authors.forename: George A
authors.initials: GA
authors.lastname: Thouas
authors.forename: David R
authors.initials: DR
authors.lastname: Nisbet
authors.forename: John S
authors.initials: JS
authors.lastname: Forsythe
mesh_terms: D000327:Adsorption / Q000187:drug effects; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D004573:Electrolytes / Q000737:chemistry*; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D018625:Microscopy, Atomic Force; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D058525:Quartz Crystal Microbalance Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D014867:Water
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004573:Electrolytes; D019922:GAP-43 Protein; D012333:RNA, Messenger; D014867:Water; D020813:Receptor, trkB