Improving the osteogenic potential of BMP-2 with hyaluronic acid hydrogel modified with integrin-specific fibronectin fragment

Marta Kisiel, Mikaël M. Martino, Manuela Ventura, Jeffrey A. Hubbell, Jöns Hilborn, Dmitri A. Ossipov

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

While human bone morphogenetic protein-2 (rhBMP-2) is a promising growth factor for bone regeneration, its clinical efficacy has recently shown to be below expectation. In order to improve the clinical translation of rhBMP-2, there exists strong motivation to engineer better delivery systems. Hyaluronic acid (HA) hydrogel is a suitable carrier for the delivery of rhBMP-2, but a major limitation of this scaffold is its low cell adhesive properties. In this study, we have determined whether covalent grafting of an integrin-specific ligands into HA hydrogel could improve cell attachment and further enhance the osteogenic potential of rhBMP-2. A structurally stabilized fibronectin (FN) fragment containing the major integrin-binding domain of full-length FN (FN III9*-10) was engineered, in order to be incorporated into HA hydrogel. Compared to non-functionalized HA hydrogel, HA-FN hydrogel remarkably improved the capacity of the material to support mesenchymal stem cell attachment and spreading. In an ectopic bone formation model in the rat, delivery of rhBMP-2 with HA-FN hydrogel resulted in the formation of twice as much bone with better organization of collagen fibers compared to delivering the growth factor in non-functionalized HA hydrogel. This engineered hydrogel carrier for rhBMP-2 can be relevant in clinical bone repair.

Original languageEnglish (US)
Pages (from-to)704-712
Number of pages9
JournalBiomaterials
Volume34
Issue number3
DOIs
StatePublished - Jan 1 2013

Keywords

  • Bone regeneration
  • Cell adhesion
  • Fibronectin
  • Hyaluronic acid hydrogel
  • Integrins
  • RhBMP-2

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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