title: Tuning Mesenchymal Stem Cell Response onto Titanium-Niobium-Hafnium Alloy by Recombinant Fibronectin Fragments.
abstract: Since metallic biomaterials used for bone replacement possess low bioactivity, the use of cell adhesive moieties is a common strategy to improve cellular response onto these surfaces. In recent years, the use of recombinant proteins has emerged as an alternative to native proteins and short peptides owing to the fact that they retain the biological potency of native proteins, while improving their stability. In the present study, we investigated the biological effect of two different recombinant fragments of fibronectin, spanning the 8-10th and 12-14th type III repeats, covalently attached to a new TiNbHf alloy using APTES silanization. The fragments were studied separately and mixed at different concentrations and compared to a linear RGD, a cyclic RGD and the full-length fibronectin protein. Cell culture studies using rat mesenchymal stem cells demonstrated that low to medium concentrations (30% and 50%) of type III 8-10th fragment mixed with type III 12-14th fragment stimulated cell spreading and proliferation compared to RGD peptides and the fragments separately. On the other hand, type III 12-14th fragment alone or mixed at low volume percentages ≤50% with type III 8-10th fragment increased alkaline phosphatase levels compared to the other molecules. These results are significant for the understanding of the role of fibronectin recombinant fragments in cell responses and thus to design bioactive coatings for biomedical applications.
authors.affiliation: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB , Diagonal 647, 08028 Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Herranz-Diez
authors.affiliation: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB , Diagonal 647, 08028 Barcelona, Spain.|Centre for Research in NanoEngineering (CRnE)-UPC , c/Pascual i Vila 15, 08028 Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Mas-Moruno
authors.affiliation: Institute for Advanced Study and Center for Integrated Protein Science, Department Chemie, Technische Universität München , Lichtenbergstrasse 4, 85747 Garching, Germany.|Max Planck Institute for Intelligent Systems , Heisenbergstrasse 3, 70569 Stuttgart, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Neubauer
authors.affiliation: Institute for Advanced Study and Center for Integrated Protein Science, Department Chemie, Technische Universität München , Lichtenbergstrasse 4, 85747 Garching, Germany.|Max Planck Institute for Intelligent Systems , Heisenbergstrasse 3, 70569 Stuttgart, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kessler
authors.affiliation: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB , Diagonal 647, 08028 Barcelona, Spain.|Centre for Research in NanoEngineering (CRnE)-UPC , c/Pascual i Vila 15, 08028 Barcelona, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Gil
authors.affiliation: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB , Diagonal 647, 08028 Barcelona, Spain.|Centre for Research in NanoEngineering (CRnE)-UPC , c/Pascual i Vila 15, 08028 Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pegueroles
authors.affiliation: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB , Diagonal 647, 08028 Barcelona, Spain.|Centre for Research in NanoEngineering (CRnE)-UPC , c/Pascual i Vila 15, 08028 Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Manero
authors.affiliation: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB , Diagonal 647, 08028 Barcelona, Spain.|Centre for Research in NanoEngineering (CRnE)-UPC , c/Pascual i Vila 15, 08028 Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Guillem-Marti
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000497:Alloys / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D005353:Fibronectins / Q000494:pharmacology*; D006195:Hafnium / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D009556:Niobium / Q000494:pharmacology; D056951:Photoelectron Spectroscopy; D058525:Quartz Crystal Microbalance Techniques; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology*; D014025:Titanium / Q000494:pharmacology
chemical_list: D000497:Alloys; D005353:Fibronectins; D011994:Recombinant Proteins; C000611998:Titanium-Niobium-Hafnium alloy; D009556:Niobium; D014025:Titanium; D000469:Alkaline Phosphatase; D006195:Hafnium
keywords: cell adhesive peptides; fibronectin; mesenchymal stem cells; recombinant protein; titanium alloy