Biodegradableα-tricalcium phosphate (α-TCP) cement based on the chelate-setting mechanism of inositol phosphate (IP6) was developed. This paper examined the effect of the milling time ofα-TCP powder on the material properties of the cement. In addition, biocompatibility of the result cementin vitrousing osteoblasts andin vivousing rabbit models will be studied as well. Theα-TCP powders were ballmilled using ZrO2beads in pure water for various durations up to 270 minutes, with a single-phaseα-TCP obtained at ballmilling for 120 minutes. The resulting cement was mostly composed ofα-TCP phase, and the compressive strength of the cement was8.5±1.1 MPa, which suggested that the cements set with keeping the crystallite phase of starting cement powder. The cell-culture test indicated that the resulting cements were biocompatible materials.In vivostudies showed that the newly formed bones increased with milling time at a slight distance from the cement specimens and grew mature at 24 weeks, and the surface of the cement was resorbed by tartrate-resistant acid phosphatase-(TRAP-)positive osteoclast-like cells until 24 weeks of implantation. The presentα-TCP cement is promising for application as a novel paste-like artificial bone with biodegradability and osteoconductivity.

The hydroxyapatite (HAp) powder preparation process was optimized to fabricate inositol phosphate-HAp (IP6-HAp) cement with enhanced mechanical properties. Starting HAp powders were synthesized via a wet chemical process. The effect of the powder preparation process on the morphology, crystallinity, median particle size, and specific surface area (SSA) of the cement powders was examined, together with the mechanical properties of the resulting cement specimens. The smallest crystallite and median particle sizes, and the highest SSA were obtained from ball-milling of as-synthesized HAp powder under wet conditions and then freeze-drying. IP6-HAp cement fabricated with this powder had a maximum compressive strength of 23.1 ± 2.1 MPa. In vivo histological studies using rabbit models revealed that the IP6-HAp cements were directly in contact with newly formed and host bones. Thus, the present chelate-setting HAp cement is promising for application as a novel paste-like artificial bone.

Hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ; HAp) is one of inorganic components of bone and teeth, and has an osteoconductivity and execellent biocompatibility. Thus, the HAp has been used as biomaterials for bone graftings. Clinically-used HAp cements are set on the basis of the acid-base reaction of Ca 4 O(PO 4 ) 2 and CaHPO 4 . This mechanism accompany the changes of pH during hardening, leading to inflammation around tissues, together with slow setting time. We have succeeded to develop novel HAp cement, which is created by mixing the HAp powder modified with inositol phosphate (IP6) and water. The present IP6-HAp cement is set based on the chelate-bonding of IP6 without the acid-base reaction. The IP6 is not only biocompatible but also has able to chelate to some metal ions as strongly as EDTA. In the present study, we fabricated four kinds of IP6-HAp cements using commercially-available HAp powders with diferent morphology and specific surface area (SSA): HAp-100 (fine particle), HAp-200 (hexagonal shape), HAp-400 (plate shape), and s-HAp (spherical shape). Among the cement specimens examined, the IP6/HAp-100 cement derived from HAp-100 powder had maximum compressive strength of 10 MPa under following condition: Powder/Liquid (P/L) ratio＝1/0.45[w/w]. The HAp-100 powder was composed of microcrystals with the highest SSA of 62.4 m 2 ･g -1 among the HAp powder used in the present work. On the other hand, the compressive strength of the IP6/HAp-200 cements showed the lowest value of 2 MPa under following condition: P/L ratio＝1/0.35[w/w]. The HAp-200 powder of a starting material was composed of hexagonal-shaped crystals, and had the lowest SSA of 7.0 m 2 ･g -1 . These results indicate that the compressive strength of novel IP6/HAp cements was affected by powder properties, especially, the morphology and SSA of starting HAp powders.

We have developed novel bioresorbable ¢-tricalcium phosphate (¢-TCP) cements on the basis of chelate-setting mechanism of inositol phosphate (IP6). The starting cement powders (IP6/¢-TCP powders) were prepared by surface-modifying ¢-TCP particles with IP6. The cement specimen was fabricated by mixing the IP6/¢-TCP powder in pure water at desired powder/ liquid ratios, and examined the effects of powder properties of the IP6/¢-TCP powder on the mechanical strength (compressive strength) of the cement specimens. We focused on the crystalline phase, particle size, specific surface area (SSA), and crystallite size among powder properties. The crystalline phase of resulting cement specimen was ¢-TCP single phase or mixture of ¢-TCP and calcium-deficient apatite (CDAp). The ¢-TCP cement with compressive strength of 13 MPa was fabricated from the finelyground ¢-TCP powders prepared by ball-milling commercially-available ¢-TCP powder for 4 h using zirconia beads with 10 mm in diameter. Meanwhile, the ¢-TCP/CDAp biphasic cement had maximum compressive strength of about 23 MPa among the examined cement specimens, it was fabricated from the ball-milled commercially-available ¢-TCP powder for 3 h using zirconia beads with 10 mm in diameter, and then for 3 h using zirconia beads with 2 mm in diameter. In order to make the determining factors of the compressive strength clear, we examined the relationship between powder properties (particle size, SSA and crystallite size) and compressive strength. The strength of the IP6/¢-TCP cement was not dependent on the particle size of the IP6/¢-TCP powder; meanwhile, the strength was enhanced with increasing SSA and decreasing crystallite size. Thus, the IP6/¢-TCP powder with higher SSA and smaller crystallite size may be useful in the fabrication of chelate-setting ¢-TCP cement with enhanced mechanical properties.

We have successfully developed novel “chelate-setting apatite cement” using hydroxyapatite (HAp) particles surface-modified with inositol phosphate (IP6) . The HAp particles surface-modified with IP6 were mixed with water (HAp/water ratio = 1.00/0.50[w/w]) to fabricate apatite cements. We have examined the biocompatibility of the apatite cement using the culture system of MC3T3-E1 cells and the rabbit model. The cell-culture test using MC3T3-E1 cells has shown that the apatite cement has noncytotoxicity. This cement has been implanted into tibiae of rabbits. When tissue response was examined histologically up to 24 weeks, new bone formation was observed around the surface of the cement. The present work demonstrates that this apatite cement is useful as a material for artificial bone grafting.

We have developed novel calcium-phosphate cements (CPCs) based on the chelate-setting mechanism of inositol phosphate (IP6) using hydroxyapatite (HAp), β-tricalcium phosphate (β-TCP) and α-TCP as starting materials. These cements (IP6-HAp, IP6-β-TCP and IP6-α-TCP cements) have different bioresorbability due to the chemical composition of starting materials. In the present study, biocompatibility and bioresorbability of the above three cements and commercially available cement (Biopex®-R) was histologically evaluated in vivo using rabbit model for 4, 8, and 24 weeks, in addition to their dissolution in vitro. The dissolution of these cements increased in the order of IP6-HAp, IP6-β-TCP and IP6-α-TCP cements. The newly-formed bones were directly in contact with both the IP6-HAp and Biopex®-R cement specimens. As for the IP6-β-TCP and IP6-α-TCP cements, newly-formed bones were formed time-dependently slightly apart from the cement specimens. Resorption rate for Biopex®-R, IP6-HAp, IP6-β-TCP, and IP6-α-TCP cements after 24 weeks implantation were of 7.2, 5.0, 13.7, and 16.2%, respectively, compared to original cements. The present chelate-setting cements with different bioresorbability are promising candidates for application as the novel CPCs.