title: BMP-2-coated mineral coated microparticles improve bone repair in atrophic non-unions.
abstract: Atrophic non-unions are a major clinical problem. Mineral coated microparticles (MCM) are electrolyte-coated hydroxyapatite particles that have been shown in vitro to bind growth factors electrostatically and enable a tuneable sustained release. Herein, we studied whether MCM can be used in vivo to apply Bone Morphogenetic Protein-2 (BMP-2) to improve bone repair of atrophic non-unions. For this purpose, atrophic non-unions were induced in femurs of CD-1 mice (n = 48). Animals either received BMP-2-coated MCM (MCM + BMP; n = 16), uncoated MCM (MCM; n = 16) or no MCM (NONE; n = 16). Bone healing was evaluated 2 and 10 weeks postoperatively by micro-computed tomographic (µCT), biomechanical, histomorphometric and immunohistochemical analyses. µCT revealed more bone volume with more highly mineralised bone in MCM + BMP femurs. Femurs of MCM + BMP animals showed a significantly higher bending stiffness compared to other groups. Histomorphometry further demonstrated that the callus of MCM + BMP femurs was larger and contained more bone and less fibrous tissue. After 10 weeks, 7 of 8 MCM + BMP femurs presented with complete osseous bridging, whereas NONE femurs exhibited a non-union rate of 100 %. Of interest, immunohistochemistry could not detect macrophages within the callus, indicating a good biocompatibility of MCM. In conclusion, the local application of BMP-2-coated MCM improved bone healing in a challenging murine non-union model and, thus, should be of clinical interest in the treatment of non-unions.
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, Saarland University, Kirrberger Strasse 1, D-66421 Homburg/Saar, Germany.marcel.orth@uks.eu.
authors.forename: M
authors.initials: M
authors.lastname: Orth
authors.forename: N J
authors.initials: NJ
authors.lastname: Kruse
authors.forename: B J
authors.initials: BJ
authors.lastname: Braun
authors.forename: C
authors.initials: C
authors.lastname: Scheuer
authors.forename: J H
authors.initials: JH
authors.lastname: Holstein
authors.forename: A
authors.initials: A
authors.lastname: Khalil
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.forename: W L
authors.initials: WL
authors.lastname: Murphy
authors.forename: T
authors.initials: T
authors.lastname: Pohlemann
authors.forename: M W
authors.initials: MW
authors.lastname: Laschke
authors.forename: M D
authors.initials: MD
authors.lastname: Menger
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D001826:Body Fluids / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002146:Bony Callus / Q000187:drug effects / Q000473:pathology; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017102:Fracture Healing / Q000187:drug effects*; D005599:Fractures, Ununited / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007700:Kinetics; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008903:Minerals / Q000494:pharmacology*; D010027:Osteotomy; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D008903:Minerals