title: The use of RANKL-coated brushite cement to stimulate bone remodelling.
abstract: Calcium phosphate cements were first proposed as synthetic bone substitutes over two decades ago, however, they are characterised by slow chemical or cellular resorption and a slow osteointegration. In contrast, bone autograft has been shown to stimulate osteoclastogenesis and angiogenesis resulting in active bone remodelling and rapid graft incorporation. Therefore, we aimed to develop a biomaterial able to release a key stimulator of the bone remodelling process, cytokine RANKL. Cylinders of brushite cement, hydroxyapatite cement and sodium alginate were loaded with RANKL either by incorporation into the cement or by coating the material with soluble RANKL. To test the biological activity of these formulations, we assessed their effectiveness in inducing osteoclast formation from RAW 264.7 monocytic cell line. Only brushite and hydroxyapatite cements coated with RANKL allowed for retaining sufficient biological activity to induce osteoclast formation. Most efficient was coating 40 mg cylinder of brushite cement with 800 ng RANKL. We have found that RANKL-coated brushite cement exhibits osteoclastogenic activity for at least 1 month at 37 degrees C. Thus, we developed a formulation of brushite cement with RANKL - a synthetic bone graft that is similar to autografts in its ability to actively induce osteoclastogenesis.
authors.affiliation: Faculty of Dentistry, McGill University, 3640 University Street, Montreal, Quebec, Canada H3A 2B2.
authors.forename: Damien
authors.initials: D
authors.lastname: Le Nihouannen
authors.forename: S Adam
authors.initials: SA
authors.lastname: Hacking
authors.forename: Uwe
authors.initials: U
authors.lastname: Gbureck
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Komarova
authors.forename: Jake E
authors.initials: JE
authors.lastname: Barralet
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001843:Bone Cements / Q000737:chemistry / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects; D002130:Calcium Phosphates / Q000737:chemistry*; D002460:Cell Line; D017886:Durapatite / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D041681:NIH 3T3 Cells; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D053245:RANK Ligand / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000464:Alginates; D001843:Bone Cements; D002130:Calcium Phosphates; D006603:Hexuronic Acids; D053245:RANK Ligand; D020723:Glucuronic Acid; D017886:Durapatite; C494366:calcium phosphate, dibasic, dihydrate