Effects of Line and Pillar Array Microengineered SiO2 Thin Films on the Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells.

A primary goal in bone tissue engineering is the design of implants that induce controlled, guided, and rapid healing. The events that normally lead to the integration of an implant into bone and determine the performance of the device occur mainly at the tissue-implant interface. Topographical surface modification of a biomaterial might be an efficient tool for inducing stem cell osteogenic differentiation and replace the use of biochemical stimuli. The main goal of this work was to develop micropatterned bioactive silica thin films to induce the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) only through topographical stimuli. Line and pillar micropatterns were developed by a combination of sol-gel/soft lithography and characterized by scanning electron microscopy, atomic force microscopy, and contact angle measurements. hMSCs were cultured onto the microfabricated thin films and flat control for up to 21 days under basal conditions. The micropatterned groups induced levels of osteogenic differentiation and expression of osteoblast-associated markers higher than those of the flat controls. Via comparison of the micropatterns, the pillars caused a stronger response of the osteogenic differentiation of hMSCs with a higher level of expression of osteoblast-associated markers, ALP activity, and extracellular matrix mineralization after the cells had been cultured for 21 days. These findings suggest that specific microtopographic cues can direct hMSCs toward osteogenic differentiation.

[1]  Melba Navarro,et al.  Development of a Biodegradable Composite Scaffold for Bone Tissue Engineering: Physicochemical, Topographical, Mechanical, Degradation, and Biological Properties , 2006 .

[2]  W. Barthlott,et al.  Purity of the sacred lotus, or escape from contamination in biological surfaces , 1997, Planta.

[3]  Milan Mrksich,et al.  Geometric cues for directing the differentiation of mesenchymal stem cells , 2010, Proceedings of the National Academy of Sciences.

[4]  C. Wilkinson,et al.  A biodegradable and biocompatible regular nanopattern for large-scale selective cell growth. , 2010, Small.

[5]  S. Tuck,et al.  The cell biology of bone metabolism , 2008, Journal of Clinical Pathology.

[6]  Hirofumi Hidai,et al.  The effect of micronscale anisotropic cross patterns on fibroblast migration. , 2010, Biomaterials.

[7]  Farshid Guilak,et al.  Nanotopography-induced changes in focal adhesions, cytoskeletal organization, and mechanical properties of human mesenchymal stem cells. , 2010, Biomaterials.

[8]  Y. Mikami,et al.  Inductive effects of dexamethasone on the mineralization and the osteoblastic gene expressions in mature osteoblast-like ROS17/2.8 cells. , 2007, Biochemical and biophysical research communications.

[9]  R. Composto,et al.  Topographic guidance of endothelial cells on silicone surfaces with micro- to nanogrooves: orientation of actin filaments and focal adhesions. , 2005, Journal of biomedical materials research. Part A.

[10]  R T Tranquillo,et al.  A methodology for the systematic and quantitative study of cell contact guidance in oriented collagen gels. Correlation of fibroblast orientation and gel birefringence. , 1993, Journal of cell science.

[11]  P. Brett,et al.  The Control of Mesenchymal Stromal Cell Osteogenic Differentiation through Modified Surfaces , 2013, Stem cells international.

[12]  G. Whitesides,et al.  FABRICATION OF GLASS MICROSTRUCTURES BY MICRO-MOLDING OF SOL-GEL PRECURSORS , 1998 .

[13]  Topological micropatterned membranes and its effect on the morphology and growth of human mesenchymal stem cells (hMSCs) , 2006 .

[14]  M. H. Fernandes,et al.  Isotropic micropatterned silica coatings on zirconia induce guided cell growth for dental implants. , 2011, Dental materials : official publication of the Academy of Dental Materials.

[15]  K. Manzoor,et al.  Osteointegration of titanium implant is sensitive to specific nanostructure morphology. , 2012, Acta biomaterialia.

[16]  A. Levchenko,et al.  Guided Cell Migration on Microtextured Substrates with Variable Local Density and Anisotropy , 2009, Advanced functional materials.

[17]  M. Sogayar,et al.  Bone Morphogenetic Proteins: structure, biological function and therapeutic applications. , 2014, Archives of biochemistry and biophysics.

[18]  Lingzhou Zhao,et al.  Effects of micropitted/nanotubular titania topographies on bone mesenchymal stem cell osteogenic differentiation. , 2012, Biomaterials.

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

[20]  Jae-Hyun Sung,et al.  BMP-2-induced Runx2 Expression Is Mediated by Dlx5, and TGF-β1 Opposes the BMP-2-induced Osteoblast Differentiation by Suppression of Dlx5 Expression* , 2003, Journal of Biological Chemistry.

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

[22]  M. Yoshinari,et al.  The attachment and growth behavior of osteoblast-like cells on microtextured surfaces. , 2003, Biomaterials.

[23]  M. H. Fernandes,et al.  Effects of density of anisotropic microstamped silica thin films on guided bone tissue regeneration--in vitro study. , 2013, Journal of biomedical materials research. Part B, Applied biomaterials.

[24]  D. Gallego-Perez,et al.  Early Spreading and Propagation of Human Bone Marrow Stem Cells on Isotropic and Anisotropic Topographies of Silica Thin Films Produced via Microstamping , 2010, Microscopy and Microanalysis.

[25]  B. Boyan,et al.  Surface microtopography regulates osteointegration: the role of implant surface microtopography in osteointegration. , 2005, The Alpha omegan.

[26]  Ali Khademhosseini,et al.  Engineering microscale topographies to control the cell-substrate interface. , 2012, Biomaterials.

[27]  Christopher J Murphy,et al.  Modulation of osteogenic differentiation in hMSCs cells by submicron topographically-patterned ridges and grooves. , 2012, Biomaterials.

[28]  N. Gadegaard,et al.  Nanoscale surfaces for the long-term maintenance of mesenchymal stem cell phenotype and multipotency. , 2011, Nature materials.

[29]  Shuvo Roy,et al.  Post microtextures accelerate cell proliferation and osteogenesis. , 2010, Acta biomaterialia.

[30]  D. Hamilton,et al.  Microfabricated Discontinuous-Edge Surface Topographies Influence Osteoblast Adhesion, Migration, Cytoskeletal Organization, and Proliferation and Enhance Matrix and Mineral Deposition In Vitro , 2006, Calcified Tissue International.

[31]  S. K. Zaidi,et al.  Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression , 2004, Oncogene.

[32]  J. Planell,et al.  Directional alignment of MG63 cells on polymer surfaces containing point microstructures. , 2007, Small.

[33]  C. Lohmann,et al.  Response of MG63 osteoblast-like cells to titanium and titanium alloy is dependent on surface roughness and composition. , 1998, Biomaterials.

[34]  M. H. Fernandes,et al.  Micropatterned silica thin films with nanohydroxyapatite micro-aggregates for guided tissue regeneration. , 2012, Dental materials : official publication of the Academy of Dental Materials.

[35]  C. Murphy,et al.  Epithelial contact guidance on well-defined micro- and nanostructured substrates , 2003, Journal of Cell Science.

[36]  Takashi Ushida,et al.  The effect of substrate microtopography on focal adhesion maturation and actin organization via the RhoA/ROCK pathway. , 2011, Biomaterials.

[37]  A Curtis,et al.  Topographical control of cells. , 1997, Biomaterials.

[38]  N. Z. Zur Nieden,et al.  In vitro differentiation of embryonic stem cells into mineralized osteoblasts. , 2003, Differentiation; research in biological diversity.

[39]  L. Bonewald,et al.  Implant Surface Characteristics Modulate Differentiation Behavior of Cells in the Osteoblastic Lineage , 1999, Advances in dental research.

[40]  B. Boyan,et al.  Titanium surface roughness alters responsiveness of MG63 osteoblast‐like cells to 1α,25‐(OH)2D3 , 1998 .

[41]  A. F. Recum,et al.  The influence of micro-topography on cellular response and the implications for silicone implants , 1996 .

[42]  J. Planell,et al.  Mesenchymal stem cell differentiation on microstructured poly (methyl methacrylate) substrates. , 2009, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[43]  J. Y. Lim Topographic control of cell response to synthetic materials , 2009 .

[44]  D. Landolt,et al.  Differential regulation of osteoblasts by substrate microstructural features. , 2005, Biomaterials.

[45]  G. Whitesides,et al.  Soft lithography for micro- and nanoscale patterning , 2010, Nature Protocols.

[46]  Manuela T. Raimondi,et al.  Controlling Self-Renewal and Differentiation of Stem Cells via Mechanical Cues , 2012, Journal of biomedicine & biotechnology.

[47]  G. Karsenty,et al.  Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation , 1997, Cell.

[48]  B. Boyan,et al.  Direct and indirect effects of microstructured titanium substrates on the induction of mesenchymal stem cell differentiation towards the osteoblast lineage. , 2010, Biomaterials.

[49]  P. Hersen,et al.  Substrate topography induces a crossover from 2D to 3D behavior in fibroblast migration. , 2009, Biophysical journal.

[50]  Bharat Bhushan,et al.  Contact angle, adhesion and friction properties of micro-and nanopatterned polymers for superhydrophobicity , 2006 .

[51]  Sungho Jin,et al.  Hydrophobic nanopillars initiate mesenchymal stem cell aggregation and osteo-differentiation. , 2011, Acta biomaterialia.

[52]  J. Jansen,et al.  Effect of microgrooved poly-l-lactic (PLA) surfaces on proliferation, cytoskeletal organization, and mineralized matrix formation of rat bone marrow cells. , 2000, Clinical oral implants research.

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

[54]  Y. Ito,et al.  Surface micropatterning to regulate cell functions. , 1999, Biomaterials.

[55]  A. Bruinink,et al.  Evaluation of early stage human bone marrow stromal proliferation, cell migration and osteogenic differentiation on μ-MIM structured stainless steel surfaces , 2013, Journal of Materials Science: Materials in Medicine.

[56]  C. Soles,et al.  Exploring cellular contact guidance using gradient nanogratings. , 2010, Biomacromolecules.

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

[58]  M. H. Fernandes,et al.  Modulation of human dermal microvascular endothelial cell and human gingival fibroblast behavior by micropatterned silica coating surfaces for zirconia dental implant applications , 2014, Science and technology of advanced materials.

[59]  M. Textor,et al.  Surface engineering approaches to micropattern surfaces for cell-based assays. , 2006, Biomaterials.

[60]  Andre Levchenko,et al.  Synergistically enhanced osteogenic differentiation of human mesenchymal stem cells by culture on nanostructured surfaces with induction media. , 2010, Biomacromolecules.

[61]  Todd C. McDevitt,et al.  Materials as stem cell regulators. , 2014, Nature materials.