Surface guidance of stem cell behavior: chemically tailored co-presentation of integrin-binding peptides stimulates osteogenic differentiation in vitro and bone formation in vivo
Autor/a
Fraioli, Roberta
Dashnyam, Khandmaa
Kim, Joong-Hyun
Pérez Antoñanzas, Roman
Kim, Hae-Won
Gil Mur, Francisco Javier
Ginebra Molins, Maria Pau
Manero Planella, José María
Mas Moruno, Carlos
Data de publicació
2016-10-01ISSN
1742-7061
Resum
Surface modification stands out as a versatile technique to create instructive biomaterials that are able to actively direct stem cell fate. Chemical functionalization of titanium has been used in this work to stimulate the differentiation of human mesenchymal stem cells (hMSCs) into the osteoblastic lineage, by covalently anchoring a synthetic double-branched molecule (PTF) to the metal that allows a finely controlled presentation of peptidic motifs. In detail, the effect of the RGD adhesive peptide and its synergy motif PHSRN is studied, comparing a random distribution of the two peptides with the chemically-tailored disposition within the custom made synthetic platform, which mimics the interspacing between the motifs observed in fibronectin. Contact angle measurement and XPS analysis are used to prove the efficiency of functionalization. We demonstrate that, by rationally designing ligands, stem cell response can be efficiently guided towards the osteogenic phenotype: In vitro, PTF-functionalized surfaces support hMSCs adhesion, with higher cell area and formation of focal contacts, expression of the integrin receptor α5β1 and the osteogenic marker Runx2, and deposition a highly mineralized matrix, reaching values of mineralization comparable to fibronectin. Our strategy is also demonstrated to be efficient in promoting new bone growth in vivo in a rat calvarial defect. These results highlight the efficacy of chemical control over the presentation of bioactive peptides; such systems may be used to engineer bioactive surfaces with improved osseointegrative properties, or can be easily tuned to generate multi-functional coatings requiring a tailored disposition of the peptidic motifs.
Tipus de document
Article
Versió del document
Versió acceptada
Llengua
Anglès
Matèries (CDU)
57 - Biologia
Paraules clau
Titani
Pèptids
Materials biomèdics
Cèl·lules mare
Adhesius
Fibronectines
Titanio
Péptidos
Materiales biomédicos
Células madre
Adhesivos
Fibronectinas
Titanium
Peptides
Biomedical materials
Stem cells
Adhesives
Fibronectins
Pàgines
32
Publicat per
Elsevier
Col·lecció
43;
Publicat a
Acta Biomaterialia
Citació
Fraioli, Roberta; Dashnyam, Khandmaa; Kim, Joong-Hyun [et al.]. Surface guidance of stem cell behavior: chemically tailored co-presentation of integrin-binding peptides stimulates osteogenic differentiation in vitro and bone formation in vivo. Acta Biomaterialia, 2016, 43, p. 269-281. Disponible en: <https://www.sciencedirect.com/science/article/abs/pii/S1742706116303841?via%3Dihub>. Fecha de acceso: 10 may. 2020. DOI: 10.1016/j.actbio.2016.07.049
Número de l'acord de la subvenció
info:eu-repo/grantAgreement/MINECO/2PE/MAT2015-67183-R
info:eu-repo/grantAgreement/EC/FP7/321985
Aquest element apareix en la col·lecció o col·leccions següent(s)
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Drets
© 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.