title: Gallium enhances reconstructive properties of a calcium phosphate bone biomaterial.
abstract: Calcium phosphate (CaP)-based biomaterials are commonly used in bone reconstructive surgery to replace the damaged tissue, and can also serve as vectors for local drug delivery. Due to its inhibitory action on osteoclasts, the semi-metallic element gallium (Ga) is used for the systemic treatment of disorders associated with accelerated bone resorption. As it was demonstrated that Ga could be incorporated in the structure of CaP biomaterials, we investigated the biological properties of Ga-loaded CaP biomaterials. Culturing bone cells on Ga-CaP, we observed a decrease in osteoclast number and a downregulation of late osteoclastic markers expression, while Ga-CaP upregulated the expression of osteoblastic marker genes involved in the maturation of bone matrix. We next investigated in vivo bone reconstructive properties of different Ga-loaded biomaterials using a murine bone defect healing model. All implanted biomaterials showed a good osseointegration into the surrounding host tissue, accompanied by a successful bone ingrowth and bone marrow reconstruction, as evidenced by histological analysis. Moreover, quantitative micro-computed tomography analysis of implants revealed that Ga enhanced total defect filling. Lastly, we took advantage for the first time of a particular mode of non-linear microscopy (second harmonic generation) to quantify in vivo bone tissue reconstruction within a CaP bone substitute. By doing so, we showed that Ga exerted a positive impact on mature organized collagen synthesis. As a whole, our data support the hypothesis that Ga represents an attractive additive to CaP biomaterials for bone reconstructive surgery. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Université Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice, France.|GRAFTYS SA, Aix en Provence, France.
authors.forename: Ivana
authors.initials: I
authors.lastname: Strazic Geljic
authors.affiliation: Université Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Melis
authors.affiliation: Université Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice, France.|GRAFTYS SA, Aix en Provence, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Boukhechba
authors.affiliation: Université Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Schaub
authors.affiliation: GRAFTYS SA, Aix en Provence, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Mellier
authors.affiliation: CNRS, CEISAM, UMR6230, Nantes, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Janvier
authors.affiliation: CCMA, Université Côte d'Azur, BP71, Nice, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Laugier
authors.affiliation: CNRS, CEISAM, UMR6230, Nantes, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bouler
authors.affiliation: LIOAD, Université de Nantes, Inserm UMR791, BP84215, Nantes, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Verron
authors.affiliation: Université Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice, France.
authors.forename: Jean-Claude
authors.identifier: 0000-0003-3773-6110
authors.initials: JC
authors.lastname: Scimeca
mesh_terms: D000818:Animals; D001031:Apatites / Q000494:pharmacology; D001672:Biocompatible Materials / Q000494:pharmacology*; D001843:Bone Cements / Q000494:pharmacology; D018786:Bone Substitutes / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D005269:Femur / Q000187:drug effects; D005708:Gallium / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats
chemical_list: D001031:Apatites; D001672:Biocompatible Materials; D001843:Bone Cements; D018786:Bone Substitutes; D002130:Calcium Phosphates; C020243:calcium phosphate; D005708:Gallium
keywords: bone reconstruction; bone repair quantification; calcium phosphate cements; gallium; gallium bone delivery; osteoclast/osteoblast crosstalk; second harmonic generation quantitative analysis