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

Cheng, Zhe A. and Alba-Perez, Andres and Gonzalez-Garcia, Cristina and Donnelly, Hannah and Llopis-Hernandez, Virginia and Jayawarna, Vineetha and Childs, Peter and Shields, David W. and Cantini, Marco and Ruiz-Cantu, Laura and Reid, Andrew and Windmill, James F. C. and Addison, Elena S. and Corr, Sandra and Marshall, William G. and Dalby, Matthew J. and Salmeron-Sanchez, Manuel (2018) Nanoscale coatings for ultralow dose BMP-2-driven regeneration of critical-sized bone defects. Advanced Science. 1800361. ISSN 2198-3844

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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 report mechanisms to drive stem cell differentiation and bone regeneration in a critical-sized murine defect model with translation to a clinical veterinary setting. 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, for the first time, 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.