title: Biodegradable Nanotopography Combined with Neurotrophic Signals Enhances Contact Guidance and Neuronal Differentiation of Human Neural Stem Cells.
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.
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea.|Department of Biomaterials Science and Engineering, Yonsei University, Seoul, 120-749, Republic of Korea.
authors.forename: Kisuk
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 330-714, Republic of Korea.
authors.forename: Esther
authors.initials: E
authors.lastname: Park
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea.
authors.forename: Jong Seung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Severance Children's Hospital, Department of Pediatrics and BK21 Plus Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea.
authors.forename: Il-Sun
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 330-714, Republic of Korea.
authors.forename: Kwonho
authors.initials: K
authors.lastname: Hong
authors.affiliation: Severance Children's Hospital, Department of Pediatrics and BK21 Plus Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea.
authors.forename: Kook In
authors.initials: KI
authors.lastname: Park
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea. seungwoocho@yonsei.ac.kr.|Department of Neurosurgery, Yonsei University College of Medicine, Seoul, 120-750, Republic of Korea. seungwoocho@yonsei.ac.kr.
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 330-714, Republic of Korea. hsyang@dankook.ac.kr.
authors.forename: Hee Seok
authors.initials: HS
authors.lastname: Yang
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties; D014867:Water / Q000737:chemistry
chemical_list: D015415:Biomarkers; D009414:Nerve Growth Factors; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: biodegradable nanotopography; contact guidance; differentiation; focal adhesion; human neural stem cells; nerve growth factor