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Biodegradable Nanotopography Combined with Neurotrophic Signals Enhances Contact Guidance and Neuronal Differentiation of Human Neural Stem Cells

 Kisuk Yang  ;  Esther Park  ;  Jong Seung Lee  ;  Il-Sun Kim  ;  Kwonho Hong  ;  Kook In Park  ;  Seung-Woo Cho  ;  Hee Seok Yang 
 Macromolecular Bioscience, Vol.15(10) : 1348-1356, 2015 
Journal Title
 Macromolecular Bioscience 
Issue Date
Biomarkers/metabolism ; Cell Differentiation/drug effects* ; Cytoskeleton/drug effects ; Cytoskeleton/metabolism ; Focal Adhesions/drug effects ; Focal Adhesions/metabolism ; Gene Expression Regulation/drug effects ; Humans ; Lactic Acid/chemistry ; Nanoparticles/chemistry* ; Nerve Growth Factors/pharmacology* ; Neural Stem Cells/cytology* ; Neural Stem Cells/drug effects ; Neurites/drug effects ; Neurites/metabolism ; Neurons/cytology* ; Neurons/drug effects ; Polyglycolic Acid/chemistry ; Surface Properties ; Water/chemistry
biodegradable nanotopography ; contact guidance ; differentiation ; focal adhesion ; human neural stem cells ; nerve growth factor
Biophysical cues provided by nanotopographical surfaces have been used as stimuli to guide neurite extension and regulate neural stem cell (NSC) differentiation. Here, we fabricated biodegradable polymer substrates with nanoscale topography for enhancing human NSC (hNSC) differentiation and guided neurite outgrowth. The substrate was constructed from biodegradable poly(lactic-co-glycolic acid) (PLGA) using solvent-assisted capillary force lithography. We found that precoating with 3,4-dihydroxy-l-phenylalanine (DOPA) facilitated the immobilization of poly-l-lysine and fibronectin on PLGA substrates via bio-inspired catechol chemistry. The DOPA-coated nanopatterned substrates directed cellular alignment along the patterned grooves by contact guidance, leading to enhanced focal adhesion, skeletal protein reorganization, and neuronal differentiation of hNSCs as indicated by highly extended neurites from cell bodies and increased expression of neuronal markers (Tuj1 and MAP2). The addition of nerve growth factor further enhanced neuronal differentiation of hNSCs, indicating a synergistic effect of biophysical and biochemical cues on NSC differentiation. These bio-inspired PLGA nanopatterned substrates could potentially be used as implantable biomaterials for improving the efficacy of hNSCs in treating neurodegenerative diseases.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Il-Sun(김일선) ORCID logo https://orcid.org/0000-0003-4033-4323
Park, Kook In(박국인) ORCID logo https://orcid.org/0000-0001-8499-9293
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