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 journalArticle

1 Citation (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 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.
LanguageEnglish
Article number1800361
Number of pages12
JournalAdvanced Science
Early online date19 Nov 2018
DOIs
Publication statusE-pub ahead of print - 19 Nov 2018

Fingerprint

Bone Morphogenetic Protein 2
regeneration
bones
Regeneration
Intercellular Signaling Peptides and Proteins
Bone
proteins
Proteins
coatings
Bone and Bones
Coatings
dosage
Defects
Bone Regeneration
defects
Stem cells
Technology
stem cells
Bone Morphogenetic Protein Receptors
Cell signaling

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
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. / Nanoscale coatings for ultralow dose BMP-2-driven regeneration of critical-sized bone defects. In: Advanced Science. 2018.
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Cheng, ZA, Alba-Perez, A, Gonzalez-Garcia, C, Donnelly, H, Llopis-Hernandez, V, Jayawarna, V, Childs, P, Shields, DW, Cantini, M, Ruiz-Cantu, L, Reid, A, Windmill, JFC, Addison, ES, Corr, S, Marshall, WG, Dalby, MJ & Salmeron-Sanchez, M 2018, 'Nanoscale coatings for ultralow dose BMP-2-driven regeneration of critical-sized bone defects' Advanced Science. https://doi.org/10.1002/advs.201800361

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.

In: Advanced Science, 19.11.2018.

Research output: Contribution to journalArticle

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

PY - 2018/11/19

Y1 - 2018/11/19

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 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.

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 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.

KW - biomaterials

KW - bone regeneration

KW - growth factor delivery

KW - stem cell differentiation

UR - https://onlinelibrary.wiley.com/journal/21983844

U2 - 10.1002/advs.201800361

DO - 10.1002/advs.201800361

M3 - Article

JO - Advanced Science

T2 - Advanced Science

JF - Advanced Science

SN - 2198-3844

M1 - 1800361

ER -

Cheng ZA, Alba-Perez A, Gonzalez-Garcia C, Donnelly H, Llopis-Hernandez V, Jayawarna V et al. Nanoscale coatings for ultralow dose BMP-2-driven regeneration of critical-sized bone defects. Advanced Science. 2018 Nov 19. 1800361. https://doi.org/10.1002/advs.201800361