In vivo mechanisms of hydroxyapatite ceramic degradation by osteoclasts: fine structural microscopy

In the present study the in vivo mechanism of calcium-phosphate (CaP) ceramic degradation has been investigated by means of transmission electron microscopy. The results revealed osteoclast-mediated degradation of hydroxyapatite ceramic implanted into sheep bone by simultaneous resorption and phagocytosis. After 6 weeks of implantation, osteoclasts were localized immediately beneath the ceramic surface. They had formed resorption lacunae and exhibited typical ultrastructural features, such as the ruffled border, the clear zone, and the dorsal microvilli. Their resorption capacity also had become evident by alterations of the electron density and the shape of the CaP crystals localized within the acidic microenvironment of the ruffled border. Moreover, the osteoclasts simultaneously were capable of phagocytosing the resorbed CaP crystals. The formation of endophagosomes was performed (1) by the uptake of particles into large intracellular vacuoles, which were generated by deep invagination of the membranes of the osteoclastic ruffled border, and (2) by the encircling of particles due to the development of pseudopodia-like plasmaprotrusions of the ruffled border. The formation of endophagosomes was followed by the in situ fragmentation of the inclusion material, which subsequently was released into the extracellular space and phagocytosed by macrophages.