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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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.

Original languageEnglish
Article number1800361
JournalAdvanced Science
Volume6
Issue number2
DOIs
Publication statusPublished - Jan 23 2019

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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