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

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1348-1356
Number of pages9
JournalMacromolecular Bioscience
Volume15
Issue number10
DOIs
Publication statusPublished - 2015 Oct 1

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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