Hydrophobic nanopillars initiate mesenchymal stem cell aggregation and osteo-differentiation.

Surface engineering approaches that alter the physical topography of a substrate could be used as an effective tool and as an alternative to biochemical means of directing stem cell interactions and their subsequent differentiation. In this paper we compare hydrophobic micro- vs. nanopillar type fabrication techniques for probing mesenchymal stem cell (MSC) interaction with the surface physical environment. The roles played by the topography of the nanopillar in particular influenced MSC growth and allowed for regulatory control of the stem cell fate. The nanopillar induced large 3-D cell aggregates to form on the surface which had up-regulated osteogenic specific matrix components. The ability to control MSC differentiation, using only the topographical factors, has a profound effect on both MSC biology and tissue engineering. This study aims to highlight the importance of the physical material carrier in stem cell based tissue engineering schemes.

[1]  K. Leong,et al.  Substrate topography shapes cell function , 2009 .

[2]  K. Leong,et al.  Biomaterials approach to expand and direct differentiation of stem cells. , 2007, Molecular therapy : the journal of the American Society of Gene Therapy.

[3]  Julie Gold,et al.  Protein Adsorption on Model Surfaces with Controlled Nanotopography and Chemistry , 2002 .

[4]  Matthew J Dalby,et al.  Genomic expression of mesenchymal stem cells to altered nanoscale topographies , 2008, Journal of The Royal Society Interface.

[5]  J. Samitier,et al.  Stem cell differentiation by functionalized micro- and nanostructured surfaces. , 2009, Nanomedicine.

[6]  Sungho Jin,et al.  Enhanced cellular mobility guided by TiO2 nanotube surfaces. , 2008, Nano letters.

[7]  C. Wilkinson,et al.  Osteoprogenitor response to defined topographies with nanoscale depths. , 2006, Biomaterials.

[8]  Jung-Woog Shin,et al.  Comparison of physical, chemical and cellular responses to nano- and micro-sized calcium silicate/poly(ϵ-caprolactone) bioactive composites , 2008, Journal of The Royal Society Interface.

[9]  Bengt Herbert Kasemo,et al.  Biological surface science , 1998 .

[10]  A. Aydın,et al.  Evaluation of the biocompatibility of various dental alloys: Part I--Toxic potentials. , 1996, The European journal of prosthodontics and restorative dentistry.

[11]  K. Anseth,et al.  The effect of heparin-functionalized PEG hydrogels on three-dimensional human mesenchymal stem cell osteogenic differentiation. , 2007, Biomaterials.

[12]  Sungho Jin,et al.  Improved bone-forming functionality on diameter-controlled TiO(2) nanotube surface. , 2009, Acta biomaterialia.

[13]  M. Hussain,et al.  Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold. , 2007, Biomaterials.

[14]  Organization of mesenchymal stem cells is controlled by micropatterned silicon substrates , 2007 .

[15]  S. Bauer,et al.  Improved attachment of mesenchymal stem cells on super-hydrophobic TiO2 nanotubes. , 2008, Acta biomaterialia.

[16]  D. Discher,et al.  Extracellular matrix elasticity directs stem cell differentiation. , 2007, Journal of musculoskeletal & neuronal interactions.

[17]  Richard Tuli,et al.  Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold. , 2005, Biomaterials.

[18]  L. Schlapbach,et al.  Protein adsorption on topographically nanostructured titanium , 2001 .

[19]  Wei-Qiang Song,et al.  Protein adsorption on materials surfaces with nano-topography , 2007 .

[20]  J. Spatz,et al.  Technique of surface modification of a cell-adhesion-resistant hydrogel by a cell-adhesion-available inorganic microarray. , 2008, Biomacromolecules.

[21]  Christophe Vieu,et al.  Electron beam lithography: resolution limits and applications , 2000 .

[22]  Jiahao Zhao,et al.  Silver catalysis in the fabrication of silicon nanowire arrays , 2006 .

[23]  L. Schlapbach,et al.  Creation of nanostructures to study the topographical dependency of protein adsorption , 2002 .

[24]  David I. Wilson,et al.  Characterization and Multipotentiality of Human Fetal Femur–Derived Cells: Implications for Skeletal Tissue Regeneration , 2006, Stem cells.

[25]  M. Dalby,et al.  Nanostructured surfaces: cell engineering and cell biology. , 2009, Nanomedicine.

[26]  Jackie Y Ying,et al.  The effect of matrix stiffness on mesenchymal stem cell differentiation in a 3D thixotropic gel. , 2010, Biomaterials.

[27]  Jian Tang,et al.  The regulation of stem cell differentiation by cell-cell contact on micropatterned material surfaces. , 2010, Biomaterials.

[28]  A S G Curtis,et al.  In vitro reaction of endothelial cells to polymer demixed nanotopography. , 2002, Biomaterials.

[29]  Joshua C. Hansen,et al.  The regulation of integrin-mediated osteoblast focal adhesion and focal adhesion kinase expression by nanoscale topography. , 2007, Biomaterials.

[30]  C. Wilkinson,et al.  The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. , 2007, Nature materials.

[31]  A. Cassie,et al.  Wettability of porous surfaces , 1944 .

[32]  Yin Wu,et al.  Uniform, axial-orientation alignment of one-dimensional single-crystal silicon nanostructure arrays. , 2005, Angewandte Chemie.

[33]  Jianguo Sun,et al.  Cell orientation on a stripe-micropatterned surface , 2009 .

[34]  Jianguo Sun,et al.  Fabrication of micropatterns of nanoarrays on a polymeric gel surface. , 2010, Nanoscale.

[35]  A. Curtis,et al.  Rapid fibroblast adhesion to 27nm high polymer demixed nano-topography. , 2004, Biomaterials.

[36]  Yunjie Yan,et al.  Synthesis of Large‐Area Silicon Nanowire Arrays via Self‐Assembling Nanoelectrochemistry , 2002 .

[37]  P. Thomsen,et al.  In vivo evaluation of noble metal coatings. , 2010, Journal of biomedical materials research. Part B, Applied biomaterials.

[38]  J. Samitier,et al.  Effects of artificial micro- and nano-structured surfaces on cell behaviour. , 2009, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[39]  Shyni Varghese,et al.  Controlled differentiation of stem cells. , 2008, Advanced drug delivery reviews.

[40]  Sungho Jin,et al.  Significantly accelerated osteoblast cell growth on aligned TiO2 nanotubes. , 2006, Journal of biomedical materials research. Part A.

[41]  M. Mrksich Tailored substrates for studies of attached cell culture , 1998, Cellular and Molecular Life Sciences CMLS.

[42]  Nikolaj Gadegaard,et al.  Nanotopographical control of human osteoprogenitor differentiation. , 2007, Current stem cell research & therapy.

[43]  D. Prockop,et al.  An Alizarin red-based assay of mineralization by adherent cells in culture: comparison with cetylpyridinium chloride extraction. , 2004, Analytical biochemistry.

[44]  David A Weitz,et al.  The cell as a material. , 2007, Current opinion in cell biology.

[45]  Christopher S. Chen,et al.  Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. , 2004, Developmental cell.

[46]  J. Y. Lim,et al.  Cell sensing and response to micro- and nanostructured surfaces produced by chemical and topographic patterning. , 2007, Tissue engineering.

[47]  Adam J. Engler,et al.  Myotubes differentiate optimally on substrates with tissue-like stiffness , 2004, The Journal of cell biology.

[48]  Sungho Jin,et al.  Stem cell fate dictated solely by altered nanotube dimension , 2009, Proceedings of the National Academy of Sciences.

[49]  Nikolaj Gadegaard,et al.  Cell signaling arising from nanotopography: implications for nanomedical devices. , 2006, Nanomedicine.

[50]  I. Asahina,et al.  Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells. , 1996, Experimental cell research.

[51]  R. N. Wenzel RESISTANCE OF SOLID SURFACES TO WETTING BY WATER , 1936 .

[52]  Xi Mao,et al.  The development and identification of constructing tissue engineered bone by seeding osteoblasts from differentiated rat marrow stromal stem cells onto three-dimensional porous nano-hydroxylapatite bone matrix in vitro. , 2005, Tissue & cell.

[53]  F. Bäckhed,et al.  Nanoscale features influence epithelial cell morphology and cytokine production. , 2003, Biomaterials.

[54]  Joachim P Spatz,et al.  Impact of order and disorder in RGD nanopatterns on cell adhesion. , 2009, Nano letters.

[55]  Mathis O. Riehle,et al.  The use of materials patterned on a nano- and micro-metric scale in cellular engineering , 2002 .

[56]  Yukio Nakamura,et al.  Mesenchymal Progenitors Able to Differentiate into Osteogenic, Chondrogenic, and/or Adipogenic Cells In Vitro Are Present in Most Primary Fibroblast‐Like Cell Populations , 2007, Stem cells.

[57]  S. Bruder,et al.  Osteogenic differentiation of purified, culture‐expanded human mesenchymal stem cells in vitro , 1997, Journal of cellular biochemistry.

[58]  Steven J. Jonas,et al.  Hydrophobic surfaces for enhanced differentiation of embryonic stem cell-derived embryoid bodies , 2008, Proceedings of the National Academy of Sciences.

[59]  Patrik Schmuki,et al.  Nanosize and vitality: TiO2 nanotube diameter directs cell fate. , 2007, Nano letters.

[60]  F. Guilak,et al.  In vitro Differentiation Potential of Mesenchymal Stem Cells , 2008, Transfusion Medicine and Hemotherapy.