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

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

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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.
Original languageEnglish
Article number1800361
Number of pages12
JournalAdvanced Science
Early online date19 Nov 2018
DOIs
Publication statusE-pub ahead of print - 19 Nov 2018

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Keywords

  • biomaterials
  • bone regeneration
  • growth factor delivery
  • stem cell differentiation

Cite this

Cheng, Z. A., Alba-Perez, A., Gonzalez-Garcia, C., Donnelly, H., Llopis-Hernandez, V., Jayawarna, V., ... Salmeron-Sanchez, M. (2018). Nanoscale coatings for ultralow dose BMP-2-driven regeneration of critical-sized bone defects. Advanced Science, [1800361]. https://doi.org/10.1002/advs.201800361