Phosphate graphene as an intrinsically osteoinductive scaffold for stem cell-driven bone regeneration

Proc Natl Acad Sci U S A. 2019 Mar 12;116(11):4855-4860. doi: 10.1073/pnas.1815434116. Epub 2019 Feb 22.

Abstract

Synthetic, resorbable scaffolds for bone regeneration have potential to transform the clinical standard of care. Here, we demonstrate that functional graphenic materials (FGMs) could serve as an osteoinductive scaffold: recruiting native cells to the site of injury and promoting differentiation into bone cells. By invoking a Lewis acid-catalyzed Arbuzov reaction, we are able to functionalize graphene oxide (GO) to produce phosphate graphenes (PGs) with unprecedented control of functional group density, mechanical properties, and counterion identity. In aqueous environments, PGs release inducerons, including Ca2+ and PO43- Calcium phosphate graphene (CaPG) intrinsically induces osteogenesis in vitro and in the presence of bone marrow stromal cells (BMSCs), can induce ectopic bone formation in vivo. Additionally, an FGM can be made by noncovalently loading GO with the growth factor recombinant human bone morphogenetic protein 2 (rhBMP-2), producing a scaffold that induces ectopic bone formation with or without BMSCs. The FGMs reported here are intrinsically inductive scaffolds with significant potential to revolutionize the regeneration of bone.

Keywords: biomimetic; bone; graphene; stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / pharmacology
  • Bone Regeneration / drug effects*
  • Cell Adhesion / drug effects
  • Cell Differentiation / drug effects
  • Graphite / chemical synthesis
  • Graphite / chemistry
  • Graphite / pharmacology*
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mice
  • NIH 3T3 Cells
  • Osseointegration / drug effects*
  • Osteogenesis / drug effects
  • Phosphates / chemical synthesis
  • Phosphates / chemistry
  • Phosphates / pharmacology*
  • RAW 264.7 Cells
  • Recombinant Proteins / pharmacology
  • Tissue Scaffolds / chemistry*
  • Transforming Growth Factor beta / pharmacology

Substances

  • Bone Morphogenetic Protein 2
  • Phosphates
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Graphite