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Acta Biomater. 2017 Jun;55:481-492. doi: 10.1016/j.actbio.2017.04.013. Epub 2017 Apr 19.

Synergistic effects of BMP-2, BMP-6 or BMP-7 with human plasma fibronectin onto hydroxyapatite coatings: A comparative study.

Author information

1
Institut de Science des Matériaux de Mulhouse (IS2M), University of Strasbourg, University of Haute-Alsace, CNRS UMR7361, Mulhouse, France.
2
Equipe de Recherche sur les Relations Matrice Extracellulaire-Cellules, ERRMECe (EA1391), Institut des Matériaux, I-MAT (FD4122), University of Cergy-Pontoise, Cergy-Pontoise, France.
3
Proteomics Platform, Institut de Biologie Paris Seine, University Pierre et Marie Curie, Paris, France.
4
Lasers Department, National Institute for Lasers, Plasma and Radiation Physics, Magurele, Ilfov, Romania.
5
Lasers Department, National Institute for Lasers, Plasma and Radiation Physics, Magurele, Ilfov, Romania; Faculty of Physics, University of Bucharest, Magurele, Ilfov, Romania.
6
Interaction of Cells and Environment (ICE) UPSP 2016 A104, VetAgro Sup, University of Lyon, Marcy l'Etoile, France.
7
NUCEL/NETCEM-Cell and Molecular Therapy Center, Department of Internal Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil.
8
NUCEL/NETCEM-Cell and Molecular Therapy Center, Department of Internal Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil; Chemistry Institute, Department of Biochemistry, University of São Paulo, São Paulo, Brazil.
9
Institut de Science des Matériaux de Mulhouse (IS2M), University of Strasbourg, University of Haute-Alsace, CNRS UMR7361, Mulhouse, France. Electronic address: karine.anselme@uha.fr.

Abstract

Design of new osteoinductive biomaterials to reproduce an optimized physiological environment capable of recruiting stem cells and instructing their fate towards the osteoblastic lineage has become a priority in orthopaedic surgery. This work aims at evaluating the bioactivity of BMP combined with human plasma fibronectin (FN/BMP) delivered in solution or coated onto titanium-hydroxyapatite (TiHA) surfaces. Herein, we focus on the comparison of in vitro osteogenic efficacy in mouse C2C12 pre-osteoblasts of three BMP members, namely: BMP-2, BMP-6 and BMP-7. In parallel, we evaluated the molecular binding strength between each BMP with FN using the Surface Plasmon Resonance (SPR) technology. The affinity of BMPs for FN was found totally different and dependent on BMP type. Indeed, the combination of FN with BMP-2 on TiHA surfaces potentiates the burst of gene-mediated osteogenic induction, while it prolongs the osteogenic activity of BMP-6 and surprisingly annihilates the BMP-7 one. These results correlate with FN/BMP affinity for TiHA, since BMP-6>BMP-2>BMP-7. In addition, by analyzing the osteogenic activity in the peri-implant environment, we showed that osteoinductive paracrine effects were significantly decreased upon (FN/BMP-6), as opposed to (FN/BMP-2) coatings. Altogether, our results support the use of FN/BMP-6 to develop a biomimetic microenvironment capable to induce osteogenic activity under physiological conditions, with minimum paracrine signalization.

STATEMENT OF SIGNIFICANCE:

The originality of our paper relies on the first direct comparison of the in vitro osteogenic potential of three osteogenic BMPs (BMP-2, -6 and -7) combined with native human plasma fibronectin delivered in solution or coated by laser transfer onto titanium hydroxyapatite surfaces. We confirm that BMP association with fibronectin enhances the osteogenic activity of BMP-2, -6 and -7, but with essential discrepancies, depending on the BMP member, and in agreement with the affinity of BMPs for fibronectin. Moreover, we bring elements to explain the origin of the BMP-2 medical life-threatening side-effects by analyzing in vitro paracrine effects. Finally, this work supports the alternative use of FN/BMP-6 to induce osteogenic activity under physiological conditions, with minimum side effects.

KEYWORDS:

BMPs; Functional coatings; Human plasma fibronectin; In vitro; Osteogenesis

PMID:
28434979
DOI:
10.1016/j.actbio.2017.04.013
[Indexed for MEDLINE]

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