title: Mimicking bone extracellular matrix: integrin-binding peptidomimetics enhance osteoblast-like cells adhesion, proliferation, and differentiation on titanium.
abstract: Interaction between the surface of implants and biological tissues is a key aspect of biomaterials research. Apart from fulfilling the non-toxicity and structural requirements, synthetic materials are asked to direct cell response, offering engineered cues that provide specific instructions to cells. This work explores the functionalization of titanium with integrin-binding peptidomimetics as a novel and powerful strategy to improve the adhesion, proliferation and differentiation of osteoblast-like cells to implant materials. Such biomimetic strategy aims at targeting integrins αvβ3 and α5β1, which are highly expressed on osteoblasts and are essential for many fundamental functions in bone tissue development. The successful grafting of the bioactive molecules on titanium is proven by contact angle measurements, X-ray photoelectron spectroscopy and fluorescent labeling. Early attachment and spreading of cells are statistically enhanced by both peptidomimetics compared to unmodified titanium, reaching values of cell adhesion comparable to those obtained with full-length extracellular matrix proteins. Moreover, an increase in alkaline phosphatase activity, and statistically higher cell proliferation and mineralization are observed on surfaces coated with the peptidomimetics. This study shows an unprecedented biological activity for low-molecular-weight ligands on titanium, and gives striking evidence of the potential of these molecules to foster bone regeneration on implant materials.
authors: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Campus Río Ebro, Edificio I+D Bloque 5, 1ª planta, C/Poeta Mariano Esquillor s/n, 50018 Zaragoza, Spain; Centre for Research in NanoEngineering (CRNE) - UPC, C/Pascual i Vila 15, 08028 Barcelona, Spain.
authors: Roberta
authors: R
authors: Fraioli
authors: Institute for Advanced Study and Center for Integrated Protein Science, Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
authors: Florian
authors: F
authors: Rechenmacher
authors: Institute for Advanced Study and Center for Integrated Protein Science, Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany.
authors: Stefanie
authors: S
authors: Neubauer
authors: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Campus Río Ebro, Edificio I+D Bloque 5, 1ª planta, C/Poeta Mariano Esquillor s/n, 50018 Zaragoza, Spain.
authors: José M
authors: JM
authors: Manero
authors: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Campus Río Ebro, Edificio I+D Bloque 5, 1ª planta, C/Poeta Mariano Esquillor s/n, 50018 Zaragoza, Spain.
authors: Javier
authors: J
authors: Gil
authors: Institute for Advanced Study and Center for Integrated Protein Science, Department Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany; Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Horst
authors: H
authors: Kessler
authors: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Campus Río Ebro, Edificio I+D Bloque 5, 1ª planta, C/Poeta Mariano Esquillor s/n, 50018 Zaragoza, Spain; Centre for Research in NanoEngineering (CRNE) - UPC, C/Pascual i Vila 15, 08028 Barcelona, Spain. Electronic address: carles.mas.moruno@upc.edu.
authors: Carlos
authors: C
authors: Mas-Moruno
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology*; D015921:Dental Implants; D016326:Extracellular Matrix Proteins / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D019030:Receptors, Vitronectin / Q000235:genetics / Q000378:metabolism*; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D020099:Coated Materials, Biocompatible; D015921:Dental Implants; D016326:Extracellular Matrix Proteins; D039302:Integrin alphaVbeta3; D057786:Peptidomimetics; D019030:Receptors, Vitronectin; C094340:integrin alphavbeta1; D014025:Titanium; D000469:Alkaline Phosphatase
keywords: Functionalization; Integrins; Osteointegration; Peptidomimetics; Titanium