title: Bone induction at physiological doses of BMP through localization by clay nanoparticle gels.
abstract: Bone Morphogenic Protein 2 (BMP2) can induce ectopic bone. This ability, which first motivated the widespread application of BMP2 in fracture healing and spinal arthrodesis has, more recently, been indicated as one of several serious adverse effects associated with the supra-physiological doses of BMP2 relied upon for clinical efficacy. Key to harnessing BMPs and other agents safely and effectively will be the ability to localize activity at a target site at substantially reduced doses. Clay (Laponite) nanoparticles can self assemble into gels under physiological conditions and bind growth factors for enhanced and localized efficacy. Here we show the ability to localize and enhance the activity of BMP2 to achieve ectopic bone formation at doses within the sub-microgram per ml range of concentrations sufficient to induce differentiation of responsive cell populations in vitro and at approximately 3000 fold lower than those employed in clinical practice.
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK.
authors.forename: D M R
authors.initials: DM
authors.lastname: Gibbs
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK.
authors.forename: C R M
authors.initials: CR
authors.lastname: Black
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK.
authors.forename: G
authors.initials: G
authors.lastname: Hulsart-Billstrom
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK.
authors.forename: P
authors.initials: P
authors.lastname: Shi
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK.
authors.forename: E
authors.initials: E
authors.lastname: Scarpa
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK. Electronic address: Richard.Oreffo@soton.ac.uk.
authors.forename: R O C
authors.initials: RO
authors.lastname: Oreffo
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK. Electronic address: jid@soton.ac.uk.
authors.forename: J I
authors.initials: JI
authors.lastname: Dawson
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation; D002460:Cell Line; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005782:Gels; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010012:Osteogenesis / Q000187:drug effects*; D017640:Silicates / Q000737:chemistry*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D005782:Gels; D017640:Silicates; C524813:laponite
keywords: Bone induction; Bone morphogenic protein; Clay gels; Drug delivery; Hydrogels; Smectites