Ultrastructural characterization of tissue response to sintered carbonate apatite in rabbit bone

Our previous in vivo and in vitro studies revealed excellent tissue biocompatibility and osteoconductivity of porous sintered carbonate apatite (CA). The present study focused on the ultrastructural details of cells involved in the degradation of CA and new bone formation. Electron microscopy indicated that multinucleated giant cells (MNGCs) were actively involved in CA resorption. MNGCs extended their irregular cytoplasmic protrusions deeply into the interstitial spaces between CA particles. Endophagosomes were formed by encircling partially dissolved or intact CA crystals via the development of pseudopodia-like cytoplasmic protrusions, the configuration of which was somewhat different from that of the typical ruffled border of bone-resorbing osteoclasts. Subsequently, most CA particles in MNGCs were irregular in shape, suggesting that acidic degradation of CA occurred mainly intracellularly. Mononuclear cells, such as macrophage-like and/or fibroblast-like cells, also took up and degraded some CA. Growth of very thin needle-like crystals was observed in close association with CA. Osteoblasts directly faced the CA and secreted osteoid matrix. At the CA-bone interface, an electron-dense and homogeneous thin layer free of collagen fibers was sometimes observed, suggesting an involvement in CA-bone bonding.