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Nanoscale Coatings for Ultralow Dose BMP-2-Driven Regeneration of Critical-Sized Bone Defects

Cheng, Zhe A.; Alba-Perez, Andres; Gonzalez-Garcia, Cristina; Donnelly, Hannah; Llopis-Hernandez, Virginia; Jayawarna, Vineetha; Childs, Peter; Shields, David W.; Cantini, Marco; Ruiz-Cantu, Laura; Reid, Andrew; Windmill, James F. C.; Addison, Elena S.; Corr, Sandra; Marshall, William G.; Dalby, Matthew J.; Salmeron-Sanchez, Manuel

Nanoscale Coatings for Ultralow Dose BMP-2-Driven Regeneration of Critical-Sized Bone Defects Thumbnail


Authors

Zhe A. Cheng

Andres Alba-Perez

Cristina Gonzalez-Garcia

Hannah Donnelly

Virginia Llopis-Hernandez

Vineetha Jayawarna

Peter Childs

David W. Shields

Marco Cantini

Andrew Reid

James F. C. Windmill

Elena S. Addison

Sandra Corr

William G. Marshall

Matthew J. Dalby

Manuel Salmeron-Sanchez



Abstract

© 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 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.

Citation

Cheng, Z. A., Alba-Perez, A., Gonzalez-Garcia, C., Donnelly, H., Llopis-Hernandez, V., Jayawarna, V., …Salmeron-Sanchez, M. (2019). Nanoscale Coatings for Ultralow Dose BMP-2-Driven Regeneration of Critical-Sized Bone Defects. Advanced Science, 6(2), Article 1800361. https://doi.org/10.1002/advs.201800361

Journal Article Type Article
Acceptance Date Oct 28, 2018
Online Publication Date Nov 19, 2018
Publication Date Jan 23, 2019
Deposit Date Dec 3, 2018
Publicly Available Date Dec 3, 2018
Journal Advanced Science
Electronic ISSN 2198-3844
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 6
Issue 2
Article Number 1800361
DOI https://doi.org/10.1002/advs.201800361
Keywords Biomaterials; Bone regeneration; Growth factor delivery; Stem cell differentiation
Public URL https://doi.org/10.1002/advs.201800361
Publisher URL https://onlinelibrary.wiley.com/doi/full/10.1002/advs.201800361

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