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

61 Citations (Scopus)

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

Fingerprint

Hyaluronic acid
Hydrogel
Hyaluronic Acid
Fibronectins
Hydrogels
Integrins
Bone
Intercellular Signaling Peptides and Proteins
Bone and Bones
Bone Regeneration
Stem cells
Mesenchymal Stromal Cells
Collagen
Osteogenesis
Scaffolds
Adhesives
Rats
Repair
Ligands
Proteins

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

Cite this

Improving the osteogenic potential of BMP-2 with hyaluronic acid hydrogel modified with integrin-specific fibronectin fragment. / Kisiel, Marta; Martino, Mikaël M.; Ventura, Manuela; Hubbell, Jeffrey A.; Hilborn, Jöns; Ossipov, Dmitri A.

In: Biomaterials, Vol. 34, No. 3, 01.01.2013, p. 704-712.

Research output: Contribution to journalArticle

Kisiel, Marta ; Martino, Mikaël M. ; Ventura, Manuela ; Hubbell, Jeffrey A. ; Hilborn, Jöns ; Ossipov, Dmitri A. / Improving the osteogenic potential of BMP-2 with hyaluronic acid hydrogel modified with integrin-specific fibronectin fragment. In: Biomaterials. 2013 ; Vol. 34, No. 3. pp. 704-712.
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