TY - JOUR
T1 - Nanoscale Coatings for Ultralow Dose BMP-2-Driven Regeneration of Critical-Sized Bone Defects
AU - Cheng, Zhe A.
AU - Alba-Perez, Andres
AU - Gonzalez-Garcia, Cristina
AU - Donnelly, Hannah
AU - Llopis-Hernandez, Virginia
AU - Jayawarna, Vineetha
AU - Childs, Peter
AU - Shields, David W.
AU - Cantini, Marco
AU - Ruiz-Cantu, Laura
AU - Reid, Andrew
AU - Windmill, James F.C.
AU - Addison, Elena S.
AU - Corr, Sandra
AU - Marshall, William G.
AU - Dalby, Matthew J.
AU - Salmeron-Sanchez, Manuel
N1 - Funding Information:
A.Z.C., A.A.-P., and C.G.-G. contributed equally to this work. The authors thank the National EPSRC XPS Users Service (NEXUS) for performing all XPS experiments. This study was supported by the European Research Council (ERC 306990), the UK Regenerative Medicine Platform (MRC grant MR/L022710/1), the UK Engineering and Physical Sciences Research Council (EPSRC EP/P001114/1) and a programme grant from Find A Better Way. µCT work was supported by the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007-2013) (grant agreement No. 615030).
Publisher Copyright:
© 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/1/23
Y1 - 2019/1/23
N2 - 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.
AB - 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.
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U2 - 10.1002/advs.201800361
DO - 10.1002/advs.201800361
M3 - Article
AN - SCOPUS:85056738049
VL - 6
JO - Advanced Science
JF - Advanced Science
SN - 2198-3844
IS - 2
M1 - 1800361
ER -