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Synergistic effects of electrospun PLLA fiber dimension and pattern on neonatal mouse cerebellum C17.2 stem cells
Authors:Liumin He  Susan Liao  Daping Quan  Kun Ma  Casey Chan  S Ramakrishna  Jiang Lu
Institution:1. Nanoscience and Nanotechnology Initiative, Division of Bioengineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore;2. Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China;3. Department of Mechanical Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore;1. Department of Polymer Science, The University of Akron, Akron, OH 44325, USA;2. Department of Chemistry, The University of Warwick, Coventry CV4 7AL, UK;3. Center for Biomaterials in Medicine, Austen Bioinnovation Institute in Akron, Akron, OH 44308, USA;1. NEST, Scuola Normale Superiore and Istituto Nanoscienze-CNR, Piazza San Silvestro 12, Pisa 56127, Italy;2. Center for Nanotechnology Innovation @ NEST, Istituto Italiano di Tecnologia, Piazza San Silvestro 12, Pisa 56127, Italy;1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China;2. Department of Chemistry, Tsinghua University, Beijing 100084, China;3. University of Chinese Academy of Sciences, Beijing 100039, China;1. Nanomaterial Research Lab, Department of Textile Engineering, Mehran University of Engineering and Technology, Jamshoro 76060, Pakistan;2. Nano Fusion Technology Research Group, Division of Frontier Fibers, Institute for Fiber Engineering (IFES), Interdisciplinary Cluster for Cutting Edge Research (ICCER), Shinshu University, Tokida 3-15-1, Ueda, Nagano Prefecture 386-8567, Japan;1. Department of Materials Science and Engineering, Johns Hopkins University, 205 Maryland Hall, Baltimore, MD 21218, USA;2. Translational Tissue Engineering Center, Johns Hopkins School of Medicine, 5002 Smith Building, Baltimore, MD 21287, USA;3. Department of Neurology and Neurosurgery, Johns Hopkins University School of Medicine, 250 Rangos Building, Baltimore, MD 21287, USA;4. Buck Institute for Research on Aging, Novato, CA 94945, USA;5. Center for Regenerative Medicine, National Institutes of Health, Bethesda, MD 20892, USA;6. Department of Neuroscience, Johns Hopkins University School of Medicine, 250 Rangos Building, Baltimore, MD 21287, USA
Abstract:Topographical features, including fiber dimensions and pattern, are important aspects in developing fibrous scaffolds for tissue engineering. In this study aligned poly(l-lactide) (PLLA) fibers with diameters of 307 ± 47, 500 ± 53, 679 ± 72 and 917 ± 84 nm and random fibers with diameters of 327 ± 40, 545 ± 54, 746 ± 82 and 1150 ± 109 nm were obtained by optimizing the electrospinning parameters. We cultured neonatal mouse cerebellum C17.2 cells on the PLLA fibers. These neural stem cells (NSCs) exhibited significantly different growth and differentiation depending upon fiber dimension and pattern. On aligned fibers cell viability and proliferation was best on 500 nm fibers, and reduced on smaller or larger fibers. However, on random fibers cell viability and proliferation was best with the smallest (350 nm) and largest (1150 nm) diameter fibers. Polarized and elongated cells were orientated along the fiber direction on the aligned fibers, with focal contacts bridging the cell body and aligned fibers. Cells of spindle and polygonal morphologies were randomly distributed on the random fibers, with no focal contacts observed. Moreover, longer neurites were obtained on the aligned fibers than random fibers within the same diameter range. Thus, the surface topographic morphologies of fibrous scaffolds, including fiber pattern, dimensions and mesh size, play roles in regulating the viability, proliferation and neurite outgrowth of NSCs. Nevertheless, our results indicated that aligned 500 nm fiber are most promising for fine tuning the design of a nerve scaffold.
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