Vancomycin (VCM), a methiciline-cefem resistant Staphylococcus aureus (MRSA)-specific antibiotic, was incorporated in a self-setting tetracalcium phosphate (TTCP)-dicalcium phosphate dihydrate (DCPD) apatite cement that hardened isothermally into a hydroxyapatite (HAP) phase with crystallinity similar to that of host bone. Effective release of VCM into PBS lasted for 2 weeks from cements containing 1% VCM and for longer than 9 weeks from cements containing 5% VCM. The rate of release of VCM differed between cements with different crystallinities as well as between the two dissolution media, PBS and simulated body fluid. Mean concentration of VCM in the bone marrow tissue released from cements containing 5% VCM was 20 times the minimum inhibitory concentration 3 weeks after implantation in bone. Direct contact with new bone was observed with the cements containing 1% VCM. Slow delivery of VCM from a self-setting TTCP-DCPD apatite cement with low crystallinity could be used to treat MRSA osteomyelitis.
Tetracalcium phosphate-dicalcium phosphate dihydrate self-setting apatite cement mixed with low-crystallized seed hydroxyapatite is similar to the host bone in degree of crystallinity. The bonding strength of this cement with hydroxyapatite-coated titanium rods was twice that with noncoated titanium and four times that with stainless steel. Histologically, TTCP-DCPD apatite cement incorporated into the tibia of rabbits were degraded, absorbed, and replaced by the normal body trabeculae rapidly. The mechanical strength of the cement disk intercalated into a gap made in the rabbit tibiae increased to 73% of that of the normal tibia at 10 weeks concurrently with the decrease in bone mineral density of the disk toward that of the normal tibia, in which bony replacement of the disk was observed also histologically. These bioactive and biodegradative characters of this cement are due to the similarity of its degree of crystallinity to that of the host bone, and could expand its clinical applications.
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