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

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., 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., & 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://nottingham-repository.worktribe.com/output/1356085
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1002/advs.201800361
• Contract Date: Dec 3, 2018