Stem Cell Aligned Growth Induced by CeO2 Nanoparticles in PLGA Scaffolds with Improved Bioactivity for Regenerative Medicine

Hybrid 2D polymeric-ceramic biosupports are fabricated by mixing a nanostructured CeO2 powder with 85:15 poly(D,L-lactic-co-glycolic acid) (PLGA)/dichloromethane solutions at specific concentrations, followed by solvent casting onto pre-patterned molds. The mold patterning allows the orientation of ceramic nanoparticles into parallel lines within the composite scaffold. The ability of the produced films to host and address cell growth is evaluated after 1,3, and 6 days of culturing with murine derived cardiac and mesenchymal stem cells (CSCs and MSCs), and compared with PLGA films without ceramics and loaded with nanostructured TiO2. Aligned cell growth is observed only for scaffolds that incorporate oriented ceramic nanoparticles, attributed to the nanoceramic ability to modulate the roughness pitch, thus improving cell sensitivity towards the host surface features. Better CSC and MSC proliferative activity is observed for CeO2 composites with respect to either TiO2-added or unfilled PLCA films. This evidence may be related to the nanostructured CeO2 antioxidative properties. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[1]  A. R. Boccaccini,et al.  Mechanical properties and bioactivity of porous PLGA/TiO2 nanoparticle-filled composites for tissue engineering scaffolds , 2007 .

[2]  Antonio Nanci,et al.  Surface Nanopatterning to Control Cell Growth , 2008 .

[3]  S. Licoccia,et al.  Sol-Gel Nanosized Semiconducting Titania-Based Powders for Thick-Film Gas Sensors , 2000 .

[4]  Jong-Chul Park,et al.  PLGA scaffold incorporated with hydroxyapatite for cartilage regeneration , 2008 .

[5]  Giovanni Vozzi,et al.  Criticality of the Biological and Physical Stimuli Array Inducing Resident Cardiac Stem Cell Determination , 2008, Stem cells.

[6]  G. Forte,et al.  Interfacing Sca-1pos Mesenchymal Stem Cells with Biocompatible Scaffolds with Different Chemical Composition and Geometry , 2009, Journal of biomedicine & biotechnology.

[7]  Giuliano Martinelli,et al.  Sol-Gel Processed TiO2-Based Nano-Sized Powders for Use in Thick-Film Gas Sensors for Atmospheric Pollutant Monitoring , 2001 .

[8]  S. Seal,et al.  Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides , 2006, Nature nanotechnology.

[9]  Andrea Bodnar,et al.  Human Endothelial Cell Life Extension by Telomerase Expression* , 1999, The Journal of Biological Chemistry.

[10]  Young-Mi Kang,et al.  Nanofiber alignment and direction of mechanical strain affect the ECM production of human ACL fibroblast. , 2005, Biomaterials.

[11]  Antonios G Mikos,et al.  Biomimetic materials for tissue engineering. , 2003, Biomaterials.

[12]  S. Seal,et al.  Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. , 2007, Chemical communications.

[13]  Martin Bastmeyer,et al.  Cell behaviour on micropatterned substrata: limits of extracellular matrix geometry for spreading and adhesion , 2004, Journal of Cell Science.

[14]  Danielle Praaning.  Intelligence in Enzyme Regulation: Promoting Consumer Confidence , 1996, Bio/Technology.

[15]  Xu-Rong Jiang,et al.  Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype , 1999, Nature Genetics.

[16]  D. L. Cochran,et al.  Osteoblast-Mediated Mineral Deposition in Culture is Dependent on Surface Microtopography , 2002, Calcified Tissue International.

[17]  L. Rogers,et al.  Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. , 2007, Cardiovascular research.

[18]  Sudipta Seal,et al.  The role of cerium redox state in the SOD mimetic activity of nanoceria. , 2008, Biomaterials.

[19]  Amit Kumar,et al.  PEGylated nanoceria as radical scavenger with tunable redox chemistry. , 2009, Journal of the American Chemical Society.

[20]  T. Ozaki,et al.  Preparation of ceria–zirconia sub-catalysts for automotive exhaust cleaning , 2000 .

[21]  M. Das,et al.  Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. , 2007, Biomaterials.

[22]  T. Ohsuna,et al.  Ultraviolet Absorption Spectra of CeO2 Nano-Particles , 1999 .

[23]  E. Traversa,et al.  Design of Electroceramics for Solid Oxides Fuel Cell Applications: Playing with Ceria , 2008 .

[24]  I. Kangasniemi,et al.  Bonelike Hydroxyapatite Induction by a Gel‐Derived Titania on a Titanium Substrate , 1994 .

[25]  Avelino Corma,et al.  Hierarchically mesostructured doped CeO2 with potential for solar-cell use , 2004, Nature materials.

[26]  G. Forte,et al.  Thick soft tissue reconstruction on highly perfusive biodegradable scaffolds. , 2010, Macromolecular bioscience.

[27]  T. Xia,et al.  Understanding biophysicochemical interactions at the nano-bio interface. , 2009, Nature materials.

[28]  F. Muller,et al.  Trends in oxidative aging theories. , 2007, Free radical biology & medicine.

[29]  Kae Sato,et al.  The use of electron beam lithographic graft-polymerization on thermoresponsive polymers for regulating the directionality of cell attachment and detachment. , 2009, Biomaterials.

[30]  Hideki Yoshikawa,et al.  Interconnected porous hydroxyapatite ceramics for bone tissue engineering , 2009, Journal of The Royal Society Interface.

[31]  R. Tarnuzzer,et al.  Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. , 2005, Nano letters.

[32]  C J Murphy,et al.  Effects of synthetic micro- and nano-structured surfaces on cell behavior. , 1999, Biomaterials.

[33]  Adriano Piattelli,et al.  Scaffold's surface geometry significantly affects human stem cell bone tissue engineering , 2008, Journal of cellular physiology.

[34]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[35]  Julian H. George,et al.  Exploring and Engineering the Cell Surface Interface , 2005, Science.

[36]  A. Boccaccini,et al.  Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[37]  Christopher J Murphy,et al.  Biological length scale topography enhances cell-substratum adhesion of human corneal epithelial cells , 2004, Journal of Cell Science.

[38]  X. Marchandise,et al.  Evaluation of human recombinant bone morphogenetic protein-2-loaded tricalcium phosphate implants in rabbits' bone defects. , 1999, Bone.

[39]  G. Forte,et al.  Tuning hierarchical architecture of 3D polymeric scaffolds for cardiac tissue engineering , 2008 .

[40]  D. Seabold,et al.  Effects of implant surface microtopography on osteoblast gene expression. , 2005, Clinical oral implants research.

[41]  J Marler,et al.  Transplantation of cells in matrices for tissue regeneration. , 1998, Advanced drug delivery reviews.

[42]  X. Miao,et al.  Porous calcium phosphate ceramics prepared by coating polyurethane foams with calcium phosphate cements , 2004 .

[43]  Piotr Jasinski,et al.  Nanocrystalline undoped ceria oxygen sensor , 2003 .

[44]  Sumona Sarkar,et al.  Development and characterization of a porous micro-patterned scaffold for vascular tissue engineering applications. , 2006, Biomaterials.

[45]  R. Narayan,et al.  Nanoceria as antioxidant: Synthesis and biomedical applications , 2008, JOM.

[46]  Julie Gold,et al.  Quantitative assessment of the response of primary derived human osteoblasts and macrophages to a range of nanotopography surfaces in a single culture model in vitro. , 2003, Biomaterials.