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)

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: Tsimbouri, Dr Monica and Salmeron-Sanchez, Professor Manuel and Dalby, Professor Matthew and Gonzalez Garcia, Dr Cristina and Llopis-Hernandez, Dr Virginia and Yang, Dr Jingli and Cheng, Dr Zhe and Cantini, Dr Marco
• 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 > School of Molecular Biosciences; 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
65373	1	Synergistic microenvironments for non-union bone defects	Matthew Dalby	Medical Research Council (MRC)	MR/L022710/1	RI MOLECULAR CELL & SYSTEMS BIOLOGY
62690	1	HEALINSYNERGY - Material-driven fibronectin fibrillogenesis to engineer synergistic growth factor microenvironments	Manuel Salmeron-Sanchez	European Research Council (ERC)	306990	ENG - BIOMEDICAL ENGINEERING