Biodegradable Nanotopography Combined with Neurotrophic Signals Enhances Contact Guidance and Neuron
최종 수정일: 2020년 9월 22일
Volume 15, October 2015, Pages 1348-1356
Impact Factor : 3.85
Kisuk Yang, Esther Park, Jong Seung Lee, Il-Sun Kim, Kwonho Hong, Kook In Park, Seung-Woo Cho,* Hee Seok Yang*
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 bioinspired 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.
biodegradable nanotopography, contact guidance, differentiation, focal adhesion, human neural stem cells, nerve growth factor