Material-driven fibronectin assembly for high-efficiency presentation of growth factors

Llopis-Hernández, V., Cantini, M. , González-García, C., Cheng, Z. A., Yang, J., Tsimbouri, P. M., García, A. J., Dalby, M. J. and Salmerón-Sánchez, M. (2016) Material-driven fibronectin assembly for high-efficiency presentation of growth factors. Science Advances, 2(8), e1600188. (doi:10.1126/sciadv.1600188) (PMID:27574702) (PMCID:PMC5001810)

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Abstract

Growth factors (GFs) are powerful signaling molecules with the potential to drive regenerative strategies, including bone repair and vascularization. However, GFs are typically delivered in soluble format at supraphysiological doses because of rapid clearance and limited therapeutic impact. These high doses have serious side effects and are expensive. Although it is well established that GF interactions with extracellular matrix proteins such as fibronectin control GF presentation and activity, a translation-ready approach to unlocking GF potential has not been realized. We demonstrate a simple, robust, and controlled material-based approach to enhance the activity of GFs during tissue healing. The underlying mechanism is based on spontaneous fibrillar organization of fibronectin driven by adsorption onto the polymer poly(ethyl acrylate). Fibrillar fibronectin on this polymer, but not a globular conformation obtained on control polymers, promotes synergistic presentation of integrin-binding sites and bound bone morphogenetic protein 2 (BMP-2), which enhances mesenchymal stem cell osteogenesis in vitro and drives full regeneration of a nonhealing bone defect in vivo at low GF concentrations. This simple and translatable technology could unlock the full regenerative potential of GF therapies while improving safety and cost-effectiveness.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and Dalby, Professor Matthew and Tsimbouri, Dr Penelope and Llopis-Hernandez, Miss Virginia and Yang, Dr Jingli and Cantini, Dr Marco and Cheng, Dr Zhe and Gonzalez Garcia, Dr Cristina
Authors: Llopis-Hernández, V., Cantini, M., González-García, C., Cheng, Z. A., Yang, J., Tsimbouri, P. M., García, A. J., Dalby, M. J., and Salmerón-Sánchez, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Science and Engineering > School of Engineering
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Science Advances
Publisher:American Association for the Advancement of Science
ISSN:2375-2548
ISSN (Online):2375-2548
Published Online:29 August 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Science Advances 2(8):e1600188
Publisher Policy:Reproduced under a Creative Commons License
Data DOI:10.5525/gla.researchdata.311

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
653731Synergistic microenvironments for non-union bone defectsMatthew DalbyMedical Research Council (MRC)MR/L022710/1RI MOLECULAR CELL & SYSTEMS BIOLOGY
626901HEALINSYNERGY - Material-driven fibronectin fibrillogenesis to engineer synergistic growth factor microenvironmentsManuel Salmeron-SanchezEuropean Research Council (ERC)306990ENG - BIOMEDICAL ENGINEERING