Heparin-dopamine functionalized graphene foam for sustained release of bone morphogenetic protein-2

J Tissue Eng Regen Med. 2018 Jun;12(6):1519-1529. doi: 10.1002/term.2681. Epub 2018 May 18.

Abstract

The recently developed three-dimensional (3D) graphene foam (GrF) is intriguing for potential bone tissue engineering applications because it provides stem cells with a 3D porous substrate for osteogenic differentiation. However, the nature of graphene's structure lacks functional groups, thus making it difficult for further modification such as immobilization or conjugation of growth factors, which are normally required to promote tissue regeneration. To explore the potential of GrF functionalization and sustained release of therapeutic proteins, we fabricated a modified 3D GrF scaffold with bio-inspired heparin-dopamine (Hepa-Dopa) molecules using a highly scalable chemical vapour deposition method. Our data indicated that Hepa-Dopa modification resulted in significantly higher bone morphogenetic protein-2 (BMP2) binding ability and longer release capacity compared with the untreated scaffolds. Importantly, the heparin-functionalized 3D GrF significantly improved the exogenous BMP2-induced osteogenic differentiation. Therefore, our study, for the first time, indicated that the 3D GrF can be biomimetically functionalized with Hepa-Dopa and be used for sustained release of BMP2, thereby inducing osteogenic differentiation and suggesting promising potential as a new multifunctional carrier for therapeutic proteins and stem cells in bone tissue engineering.

Keywords: bone morphogenetic protein-2 (BMP2); bone tissue engineering; drug delivery; graphene foam; heparin; osteogenic differentiation.

Publication types

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

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Delayed-Action Preparations / pharmacology
  • Dopamine / chemistry*
  • Graphite / chemistry*
  • Heparin / chemistry*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Osteogenesis / drug effects
  • Tissue Scaffolds / chemistry

Substances

  • Bone Morphogenetic Protein 2
  • Delayed-Action Preparations
  • Graphite
  • Heparin
  • Alkaline Phosphatase
  • Dopamine