title: Ex Vivo bone formation in bovine trabecular bone cultured in a dynamic 3D bioreactor is enhanced by compressive mechanical strain.
abstract: Our aim was to test cell and trabecular responses to mechanical loading in vitro in a tissue bone explant culture model. We used a new three-dimensional culture model, the ZetOS system, which provides the ability to exert cyclic compression on cancellous bone cylinders (bovine sternum) cultured in forced flow circumfusion chambers, and allows to assess mechanical parameters of the cultivated samples. We evaluated bone cellular parameters through osteocyte viability test, gene and protein expression, and histomorphometric bone formation rate, in nonloaded versus loaded samples. The microarchitecture of bone cores was appraised by in vivo micro-CT imaging. After 3 weeks, the samples receiving daily cyclic compression exhibited increased osteoblast differentiation and activity associated with thicker, more plate-like-shaped trabeculae and higher Young's modulus and ultimate force as compared to unloaded samples. Osteoclast activity was not affected by mechanical strain, although it was responsive to drug treatments (retinoic acid and bisphosphonate) during the first 2 weeks of culture. Thus, in the ZetOS apparatus, we reproduce in vitro the osteogenic effects of mechanical strain known in vivo, making this system a unique and an essential laboratory aid for ex vivo testing of lamellar bone remodeling.
authors.affiliation: INSERM U890, Laboratoire de Biologie du Tissu Osseux, IFR143, IFRESIS, Université Jean Monnet, St. Etienne, F-42023, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: David
authors.forename: Alain
authors.initials: A
authors.lastname: Guignandon
authors.forename: Aline
authors.initials: A
authors.lastname: Martin
authors.forename: Luc
authors.initials: L
authors.lastname: Malaval
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Lafage-Proust
authors.forename: Aline
authors.initials: A
authors.lastname: Rattner
authors.forename: Val
authors.initials: V
authors.lastname: Mann
authors.forename: Brendon
authors.initials: B
authors.lastname: Noble
authors.forename: David B
authors.initials: DB
authors.lastname: Jones
authors.forename: Laurence
authors.initials: L
authors.lastname: Vico
mesh_terms: D000818:Animals; D019149:Bioreactors; D016723:Bone Remodeling; D001842:Bone and Bones / Q000166:cytology*; D002417:Cattle; D002454:Cell Differentiation; D019245:Compressive Strength; D010006:Osteoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology*; D010012:Osteogenesis; D013314:Stress, Mechanical; D013997:Time Factors; D046509:Tissue Culture Techniques