Nanoscale coatings for ultralow dose BMP‐2‐driven regeneration of critical‐sized bone defects

Cheng, Z. A. et al. (2019) Nanoscale coatings for ultralow dose BMP‐2‐driven regeneration of critical‐sized bone defects. Advanced Science, 6(2), 1800361. (doi:10.1002/advs.201800361) (PMID:30693176) (PMCID:PMC6343071)

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Abstract

While new biomaterials for regenerative therapies are being reported in the literature, clinical translation is slow. Some existing regenerative approaches rely on high doses of growth factors, such as bone morphogenetic protein‐2 (BMP‐2) in bone regeneration, which can cause serious side effects. An ultralow‐dose growth factor technology is described yielding high bioactivity based on a simple polymer, poly(ethyl acrylate) (PEA), and mechanisms to drive stem cell differentiation and bone regeneration in a critical‐sized murine defect model with translation to a clinical veterinary setting are reported. This material‐based technology triggers spontaneous fibronectin organization and stimulates growth factor signalling, enabling synergistic integrin and BMP‐2 receptor activation in mesenchymal stem cells. To translate this technology, plasma‐polymerized PEA is used on 2D and 3D substrates to enhance cell signalling in vitro, showing the complete healing of a critical‐sized bone injury in mice in vivo. Efficacy is demonstrated in a Münsterländer dog with a nonhealing humerus fracture, establishing the clinical translation of advanced ultralow‐dose growth factor treatment.

Item Type:Articles
Additional Information:μCT work was supported by the European Research Council (ERC) under the European Union's Seventh Framework Programme (FP7/2007-2013) (grant agreement No. [615030]).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and Jayawarna, Dr Vineetha and Childs, Dr Peter and Dalby, Professor Matthew and Marshall, Mr William and DONNELLY, HANNAH and Llopis-Hernandez, Dr Virginia and Corr, Sandra and Addison, Miss Elena and Cantini, Dr Marco and Cheng, Dr Zhe and Shields, Mr David and Alba Perez, Dr Andres and Gonzalez Garcia, Dr Cristina
Authors: Cheng, Z. A., Alba-Perez, A., Gonzalez-Garcia, C., Donnelly, H., Llopis-Hernandez, V., Jayawarna, V., Childs, P., Shields, D. W., Cantini, M., Ruiz-Cantu, L., Reid, A., Windmill, J. F.C., Addison, E. S., Corr, S., Marshall, W. G., Dalby, M. J., and Salmeron-Sanchez, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Advanced Science
Publisher:Wiley
ISSN:2198-3844
ISSN (Online):2198-3844
Published Online:19 November 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Advanced Science 6(2):1800361
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
626901HEALINSYNERGY - Material-driven fibronectin fibrillogenesis to engineer synergisticgrowth factor microenvironmentsManuel Salmeron-SanchezEuropean Research Council (ERC)306990ENG - BIOMEDICAL ENGINEERING
653731Synergistic microenvironments for non-union bone defectsMatthew DalbyMedical Research Council (MRC)MR/L022710/1RI MOLECULAR CELL & SYSTEMS BIOLOGY
722061Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - BIOMEDICAL ENGINEERING