Osteoinductive Properties of Micro Macroporous Biphasic Calcium Phosphate Bioceramics

Abstract. We have developed 17 years ago, with the collaboration of Lynch, Nery, and Legeros in USA, a bioactive concept based on biphasic calcium phosphate ceramics (BCP). The concept is determined by an optimum balance of the more stable phase of HA and more soluble TCP. The material is soluble and gradually dissolves in the body, seeding new bone formation as it releases calcium and phosphate ions into the biological medium. The bioactive concept based on the dissolution/transformation processes of HA and TCP with a specific microstructure (micropore) and macrostructure (mesopores and macropores) represents a dynamic process, including physico-chemical processes, crystal/proteins interactions, cells and tissue colonization, bone remodelling, finally contributing to ingrowth at the expense of the MBCP. The microstructure of such material is achieved with low temperature sintering conditions preserving the microstructure. The material has shown osteoconductive properties largely reported in the literature, but its osteionductive properties have not been explored and documented for such bioceramics (Triosite O Zimmer). This paper presents retrospectives series of animal data (rats, rabbits, dogs, cats) demonstrating that promotion of the mineralization into micropores occurred simultaneously with osteoid and bone ingrowth into mesopores and macropores in non bony sites. Introduction Synthetic calcium phosphate bioceramics are attracting more interest in bone reconstruction due to their unlimited availability, excellent biocompatibilty, osteo-conductivity and even more recently reported osteo-inductivity. Macroporous biphasic calcium phosphate MBCP, a mixture of hydroxyapatite (HA) and beta tricalcium phosphate ( b-TCP) was developed 20 years ago by Lynch, Nery, Legeros and Daculsi [1]. MBCP bioceramics have been largely used as bone substitutes and represent the largest bibliography on this concept of bioceramics. However, data on its potential osteoinductive properties have not been reported to date. The mechanism of osteoinduction by biomaterials is not understood and the amount of induced bone might be too limited for the reconstruction of large skeletal defects. It has been shown recently that some calcium phosphate bioceramics and coatings on metal implants can induce ectopic bone formation after implantation in muscles of different animals.[2-10] These biomaterials have demonstrated the ability to induce bone intramuscularly within their porosity in 6-12 weeks without the addition of osteogenic cells or growth factors prior to implantation. Implanted in critical size osseous defects, these osteoinductive biomaterials have demonstrated superior bone healing capacities than conventional bioceramics and coatings. Previous investigations from our group and others laboratories have shown that the implants should exhibit two features to induce ectopic bone: (i) a calcium phosphate surface with micropores and (ii) a macroporous structure.