title: A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: part I.
abstract: The study presented here investigated hydroxyapatite biomaterials implanted in soft-tissue sites in adult sheep to determine whether these materials are osteoinductive and whether the rate of osteoinduction can be increased by manipulating the composition and porosity of the implants. For the study, 16.8-mm x 5-mm discs were prepared from mixtures of hydroxyapatite and beta-tricalcium phosphate. Five mixtures of hydroxyapatite-ceramic and hydroxyapatite-cement paste forms were studied: 100 percent hydroxyapatite-ceramic (Interpore), 60 percent hydroxyapatite-ceramic, 100 percent hydroxyapatite-cement paste, 60 percent hydroxyapatite-cement paste, and 20 percent hydroxyapatite-cement paste. Biomaterials were implanted in subcutaneous and intramuscular soft-tissue pockets in 10 adult sheep. Cranial bone grafts of equal dimension were implanted as controls. One year after implantation, the volume of all biomaterials and bone grafts was determined from a computed tomographic scan, and porosity and bone formation were determined using backscatter electron microscopy. Cranial bone and the 20 percent hydroxyapatite-cement paste implants demonstrated significant volume reduction in all sites after 1 year (p < 0.001). No significant difference in volume of the remaining four biomaterials was found. There was no significant change in pore size in the ceramic implants (range, 200 to 300 micro) and in the cement-paste implants containing 60 percent hydroxyapatite or more (range, 3 to 5 nm). Pore size in the cement-paste implants containing 20 percent hydroxyapatite increased significantly with resorption of the tricalcium-phosphate component, reaching a maximum of 200 to 300 micro in the periphery, where the greatest tricalcium-phosphate resorption had occurred. Both ceramic biomaterials demonstrated lamellar bone deposition within well-formed haversian systems through the entire depth of the implants, ranging from a mean of 6.6 percent to 11.7 percent. There was minimal bone formation in the cement-paste implants containing 60 percent hydroxyapatite or more. In contrast, cement-paste implants containing 20 percent hydroxyapatite demonstrated up to 10 percent bone replacement, which was greatest in the periphery of the implants where the greatest tricalcium-phosphate resorption had occurred. This study confirms the occurrence of true osteoinduction within hydroxyapatite-derived biomaterials, when examined using backscatter techniques. In this study, the rate of osteoinduction was greatest when a porous architecture was maintained, which was best achieved in ceramic rather than cement-paste forms of hydroxyapatite. Porosity and resultant bone formation in cement-paste implants can be improved by combining hydroxyapatite with a rapidly resorbing component, such as tricalcium phosphate.
authors.affiliation: Department of Plastic Surgery, Medical College of Wisconsin, Milwaukee, 53226, USA. akgosain@mcw.edu
authors.forename: Arun K
authors.initials: AK
authors.lastname: Gosain
authors.forename: Liansheng
authors.initials: L
authors.lastname: Song
authors.forename: Paul
authors.initials: P
authors.lastname: Riordan
authors.forename: Marco T
authors.initials: MT
authors.lastname: Amarante
authors.forename: Paul G
authors.initials: PG
authors.lastname: Nagy
authors.forename: Charles R
authors.initials: CR
authors.lastname: Wilson
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Toth
authors.forename: John L
authors.initials: JL
authors.lastname: Ricci
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D016025:Bone Transplantation; D002130:Calcium Phosphates; D002516:Ceramics; D003238:Connective Tissue / Q000601:surgery; D017886:Durapatite / Q000737:chemistry; D004577:Electron Probe Microanalysis; D005260:Female; D007091:Image Processing, Computer-Assisted; D017348:Microscopy, Electron, Scanning Transmission; D018482:Muscle, Skeletal / Q000601:surgery; D010012:Osteogenesis; D016062:Porosity; D019736:Prostheses and Implants; D012756:Sheep; D014057:Tomography, X-Ray Computed
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; C485817:beta-tricalcium phosphate; D017886:Durapatite; C018392:tricalcium phosphate