title: Ectopic bone formation by microporous calcium phosphate ceramic particles in sheep muscles.
abstract: Calcium phosphate ceramics are widely used in bone reconstructive surgery because of their osteconductive properties. However, these materials generally lack osteoinductive properties required to support bone healing in large defects. In this article, we study the osteoinductive potential of calcium phosphate ceramic particles implanted for 6 months into the dorsal muscles of eight adult female sheep. Microporous biphasic calcium phosphate (MBCP) granules of 1-2 mm composed of hydroxyapatite and beta-tricalcium phosphate (60/40) had macropores of 450 microm, micropores of 0.43 microm, and a specific surface area of 1.8 m(2)/g. After 6 months in the back muscles of sheep, the explants composed of MBCP granules were hard and encapsulated by normal muscle tissue. Ectopic bone formation with Haversian structures was observed in close contact with the MBCP granules in histological sections. Back-scattered electron microscopy and micro-computed tomography indicated that approximately 10% of well-mineralized bone with mature osteocytes had formed between or upon the granules. The ectopic bone showed trabeculae bridging the MBCP granules. Both the number and thickness of the trabeculae formed between the MBCP particles were comparable to those measured in spongious bone. The overall results therefore confirmed the presence of mature bone after intramuscular implantation of MBCP granules. The different hypotheses explaining ectopic bone formation induced by MBCP granules are discussed. Synthetic bone substitutes with osteoinductive properties could be used in bone reconstructive surgery.
authors.affiliation: INSERM EM9903, Osteoarticular and Dental Tissue Engineering, Faculty of Dental Surgery of Nantes, Place Alexis Ricordeau, 44042 Nantes, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Le Nihouannen
authors.forename: Guy
authors.initials: G
authors.lastname: Daculsi
authors.forename: Afchine
authors.initials: A
authors.lastname: Saffarzadeh
authors.forename: Olivier
authors.initials: O
authors.lastname: Gauthier
authors.forename: Séverine
authors.initials: S
authors.lastname: Delplace
authors.forename: Paul
authors.initials: P
authors.lastname: Pilet
authors.forename: Pierre
authors.initials: P
authors.lastname: Layrolle
mesh_terms: D000818:Animals; D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001842:Bone and Bones / Q000033:anatomy & histology / Q000737:chemistry / Q000648:ultrastructure; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D003094:Collagen / Q000032:analysis; D005260:Female; D006882:Hydroxyapatites / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D020007:Implants, Experimental; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000601:surgery / Q000648:ultrastructure; D009999:Ossification, Heterotopic / Q000139:chemically induced*; D010011:Osteocytes / Q000166:cytology; D012756:Sheep; D014057:Tomography, X-Ray Computed
chemical_list: D018786:Bone Substitutes; D002130:Calcium Phosphates; D006882:Hydroxyapatites; C094280:hydroxyapatite-tricalciumphosphate composite; D003094:Collagen