Youji Miyamoto

Non-decay type fast-setting calcium phosphate cement: composite with sodium alginate.

Non-decay type fast-setting calcium phosphate cement (nd-FSCPC) was prepared by introducing sodium alginate (0-2.0 wt%) into the liquid phase of FSCPC. nd-FSCPC was stable even when the cement paste was immersed in distilled water immediately after mixing, whereas conventional FSCPC (c-FSCPC) decayed completely within 1 min upon immersion. The setting time of the cement, approximately 5 min, was not dependent on the presence of sodium alginate. In contrast, the introduction of sodium alginate into conventional CPC, i.e. CPC without neutral phosphate in the liquid phase, resulted in no setting when the amount of sodium alginate introduced was more than 1 wt%. Powder X-ray diffraction analysis revealed no significant difference for the conversion of cement to apatite for any concentrations of sodium alginate studied (0-2.0 wt%). The mechanical strength of the cement increased rapidly with the addition of sodium alginate up to 0.8 wt% when the cement paste was immersed and kept in distilled water at 37 degrees C, whereas further addition of sodium alginate decreased the mechanical strength. The results obtained in this investigation, taken together with sodium alginates known excellent biocompatibility and absorption behaviour, indicate that the use of sodium alginate composite FSCPC as nd-FSCPC should be of value in orthodontics and oral and maxillofacial surgery where the cement is exposed to blood.

In vivo setting behaviour of fast-setting calcium phosphate cement

The in vivo setting behaviour of fast-setting calcium phosphate cement (FSCPC) between femoral muscles of the rat was investigated to evaluate the possible value of FSCPC for medical and dental application. Conventional CPC (c-CPC) and FSCPC were implanted between femoral muscles, and various aspects of the setting behaviour such as setting time, mechanical strength and conversion ratio of cement into hydroxyapatite (HAP: Ca10(PO4)6(OH)2) were measured by the Vicat needle method, diametral tensile strength (DTS) measurement, and quantitative powder X-ray diffraction (XRD) analysis, respectively. The setting time of FSCPC in vivo was 5-7 min, in contrast to 48 min for c-CPC. As a result of its fast setting, set specimens of FSCPC showed higher mechanical strength from the initial stage than c-CPC. Higher DTS values were observed in FSCPC than c-CPC implanted after 24 h. Powder XRD analysis revealed faster conversion of FSCPC than c-CPC into HAP, which was responsible both for the faster setting and higher mechanical strength from the initial stage. We concluded, therefore, that FSCPC may be used for a wide range of clinical applications, i.e. fields where fast setting is required such as orthopaedic, plastic and reconstructive, and oral and maxillofacial surgery.

Histological and compositional evaluations of three types of calcium phosphate cements when implanted in subcutaneous tissue immediately after mixing

To evaluate the soft tissue response of calcium phosphate cement (CPC), consisting of an equimolar mixture of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) under conditions close to those encountered in actual surgical procedures, we implanted three types of CPC [conventional CPC (c-CPC), fast-setting CPC (FSCPC), and antiwashout type FSCPC (aw-FSCPC; formerly called nondecay type FSCPC or nd-FSCPC)] subcutaneously in the abdomens of rats immediately (1 min) after mixing. At 1 week after surgery, histological examination and compositional analysis were performed using light microscopy and powder X-ray diffraction (XRD), respectively. The implanted c-CPC was crumbled completely, whereas FSCPC and aw-FSCPC retained their shape. Large vesicles containing copious inflammatory effusion were subcutaneously formed around the c-CPC. Histologically, many foreign-body giant cells were collected around the c-CPC, and moderate inflammatory cell infiltration was observed at 1 week after surgery. In contrast, the FSCPC and aw-FSCPC were covered with a thin layer of granulation tissue that included few giant cells and presented slight inflammatory cell infiltration, and no effusion was observed. The XRD analysis of the c-CPC revealed the presence of some unreacted DCPA even 1 week after implantation, whereas almost no DCPA was found in the FSCPC or aw-FSCPC. In conclusion, it was found that CPC does not always show excellent tissue response. When c-CPC is implanted subcutaneously in rats immediately after mixing, it fails to set and causes a severe inflammatory response. Therefore, the type of CPC should be chosen according to the clinical particulars. CPC should be used in a manner that assures its setting reaction. We recommend the use of FSCPC and aw-FSCPC for surgical applications, such as orthopedics, plastic and reconstructive surgery, and oral and maxillofacial surgery, where the cement might otherwise crumble due to the pressure before setting.

Non-decay type fast-setting calcium phosphate cement: Hydroxyapatite putty containing an increased amount of sodium alginate

A hydroxyapatite [(HAP) Ca10(PO4)6(OH)2] putty that behaves like a putty or self-curing resin was made by increasing the amount of sodium alginate in non-decay type fast-setting calcium phosphate cement (nd-FSCPC). nd-FSCPC became viscous as the sodium alginate concentration was increased. The best handling properties were obtained when nd-FSCPC contained 8% sodium alginate in its liquid phase. When a 2-kg glass plate was placed on the paste, HAP putty spread to form an area three times that of FSCPC paste. Thus, HAP putty is expected to be easier to use than FSCPC in the filling of bone defects. HAP putty did not decay; in fact, it set within approximately 20 min when immersed in distilled water immediately after mixing. The wet diametral tensile strength value of HAP putty was approximately 12 MPa after 24 h, the same as that for nd-FSCPC containing 0.5% sodium alginate in its liquid phase, or FSCPC that is free from sodium alginate. The elements constituting set HAP putty were examined using powder X-ray diffraction and found to be predominantly apatitic minerals after 24 h. Since the handling properties of a putty or self-curing resin-like cement are very useful in certain surgical procedures, HAP putty made by increasing the sodium alginate concentration in nd-FSCPC is potentially a valuable new biomaterial for use in plastic and reconstructive surgery, as well as oral and maxillofacial surgery.

Basic properties of calcium phosphate cement containing atelocollagen in its liquid or powder phases

The basic properties of calcium phosphate cement (CPC) containing atelocollagen, the main component of the organic substrate in bone, were studied in an initial evaluation for the fabrication of modified CPC. The setting time of conventional CPC (c-CPC) was prolonged to over 100 min when c-CPC contained 1% or more atelocollagen. The diametral tensile strength (DTS) of c-CPC decreased linearly with the collagen content, descending to below the detection limit when the c-CPC contained 3% or more atelocollagen. Therefore, use of c-CPC as the base cement seems inappropriate for the fabrication of atelocollagen-containing CPC. In contrast, the cement set at 9-34 min when fast-setting CPC (FSCPC) was used as the base cement and contained 1-5% atelocollagen, respectively. Although addition of atelocollagen resulted in the decrease of DTS of the set mass, the DTS was approximately the same, 6-8 MPa, at contents of atelocollagen between 1% and 5%. When atelocollagen was added to FSCPC, the handling property was improved significantly. The paste also became more adhesive with increase in atelocollagen content. These properties are desirable for its use in surgical procedures since, for example, bony defects can be filled easily and without a space interposed between the bone and cement paste. Although there are some disadvantages for the addition of atelocollagen to CPC, it can be accepted as long as FSCPC was used as the base cement. We conclude that further evaluations of the effects of atelocollagen, such as biocompatibility, bone synthesis, and bone replacement behaviour should be done, using FSCPC as the base cement.

Fracture mechanisms of retrieved titanium screw thread in dental implant

Titanium and its alloy are increasingly attracting attention for use as biomaterials. However, delayed fracture of titanium dental implants has been reported, and factors affecting the acceleration of corrosion and fatigue have to be determined. The fractured surface of a retrieved titanium screw and metallurgical structures of a dental implant system were analyzed. The outer surface of the retrieved screw had a structure different from that of the as-received screw. It was confirmed that a shear crack initiated at the root of the thread and propagated into the inner section of the screw. Gas chromatography revealed that the retrieved screw had absorbed a higher amount of hydrogen than the as-received sample. The grain structure of a titanium screw, immersed in a solution known to induce hydrogen absorption, showed features similar to those of the retrieved screw. It was concluded that titanium in a biological environment absorbs hydrogen and this may be the reason for delayed fracture of a titanium implant.

Effects of added antibiotics on the basic properties of anti-washout-type fast-setting calcium phosphate cement.

The effect of added antibiotics on the basic properties of anti-washout-type fast-setting calcium phosphate cement (aw-FSCPC) was investigated in a preliminary evaluation of aw-FSCPC containing drugs. Flomoxef sodium was employed as the antibiotic and was incorporated into the powder-phase aw-FSCPC at up to 10%. The setting time, consistency, wet diametral tensile strength (DTS) value, and porosity were measured for aw-FSCPC containing various amounts of flomoxef sodium. X-ray diffraction (XRD) analysis was also conducted for the identification of products. To evaluate the drug-release profile, set aw-FSCPC was immersed in saline and the released flomoxef sodium was determined at regular intervals. The spread area of the cement paste as an index of consistency of the cement increased progressively with the addition of flomoxef sodium, and it doubled when the aw-FSCPC contained 8% flomoxef sodium. In contrast, the wet DTS value decreased with increase in flomoxef sodium content. Bulk density measurement and scanning electron microscopic observation revealed that the set mass was more porous with the amount of flomoxef sodium contained in the aw-FSCPC. The XRD analysis revealed that formation of hydroxyapatite (HAP) from aw-FSCPC was reduced even after 24 h, when the aw-FSCPC contained flomoxef sodium at > or = 6%. Therefore, the decrease of wet DTS value was thought to be partly the result of the increased porosity and inhibition of HAP formation in aw-FSCPC containing large amounts of flomoxef sodium. The flomoxef sodium release from aw-FSCPC showed the typical profile observed in a skeleton-type drug delivery system (DDS). The rate of drug release from aw-FSCPC can be controlled by changing the concentration of sodium alginate. Although flomoxef sodium addition has certain disadvantageous effects on the basic properties of aw-FSCPC, we conclude that aw-FSCPC is a good candidate for potential use as a DDS carrier that may be useful in surgical operations.

Tissue response to fast-setting calcium phosphate cement in bone

Fast-setting calcium phosphate cement (FSCPC) is a promising new bioactive cement with a significantly short setting time (approximately 5-6 min) compared to conventional calcium phosphate cement (c-CPC) (30-60 min) at physiologic temperatures. As a result of its ability to set quickly, it is applicable in surgical procedures where fast setting is required. In this study, FSCPC was implanted in rat tibiae to evaluate tissue response and biocompatibility. FSCPC was converted to hydroxyapatite (HAP) in bone faster than c-CPC in the first 6 h. By 24 h, significant amounts of both FSCPC and c-CPC had been converted to HAP. The conversion of FSCPC into HAP further proceeded gradually, reaching 100% within 8 weeks. Infrared spectroscopic analysis disclosed the deposition of B-type carbonate apatite, which is a biological apatite contained in human dentin or bone, on the surface of the FSCPC. Histologically, FSCPC showed a tissue response similar to that of c-CPC. A slight inflammatory reaction was observed in the soft tissue apposed to both cements in the early period, and new bone was formed along the surface of the FSCPC at the adjacent bone. However, no resorption of either cement by osteoclasts or macrophages was observed within 8 weeks. We conclude that FSCPC is superior to c-CPC in clinical applications in oral and maxillofacial, orthopedic, plastic, and reconstructive surgery, since it shows a faster setting time and higher mechanical strength in the early period that are required in these surgical procedures, as well as osteoconductivity and excellent biocompatibility similar to that of c-CPC.

Fabrication of Zn containing apatite cement and its initial evaluation using human osteoblastic cells.

Recently, the effects of Zn2+ on osteogenesis stimulation have become major topics in the research fields of bone formation and organism essential elements. Based on the fundamental finding of Zn2+ with respect to osteogenesis stimulation, Ito et al. have prepared Zn doped beta-tricalcium phosphate (ZnTCP) and have reported that ZnTCP enhances the proliferation of MC3T3-E1 cells. In this investigation, we studied the effects of ZnTCP added to apatite cement (AC) with respect to its setting reaction and proliferation of human osteoblastic cells as an initial evaluation for the feasibility of AC containing ZnTCP. Compositional analysis using powder X-ray diffractometer revealed that ZnTCP shows no reactivity with the setting reaction of AC. As a result, the mechanical strength of set AC decreased increasing amounts of added ZnTCP as if ZnTCP acts as a pore in AC. The setting time of AC was not affected by addition of ZnTCP up to 10%. When AC containing ZnTCP was immersed in alpha-MEM containing 10% bovine serum, Zn2+ was released from AC. Larger amounts of Zn2+ were released from AC containing larger amounts of ZnTCP. When human osteoblastic cells were incubated on the surface of AC discs, proliferation of human osteoblastic cells was significantly increased on the surface of AC that contained 5% ZnTCP when compared with that containing no ZnTCP. In contrast, proliferation of human osteoblastic cells decreased on the surface of AC that contained 10% ZnTCP when compared with that free from ZnTCP; indicating cytotoxicity. We concluded therefore, that addition of ZnTCP to AC is useful to enhance the osteoconductivity of AC when release of Zn2+ can be carefully regulated.

Initial histological evaluation of anti-washout type fast-setting calcium phosphate cement following subcutaneous implantation

Anti-washout-type fast-setting calcium phosphate cement using chitosan (aw-FSCPC(chi)), conventional CPC (c-CPC), CPC mixed with citric acid (CPC(citric)) and CPC mixed with polyacrylic acid (CPC(acrylic)) were implanted subcutaneously in rats immediately after mixing to shed some light on the understanding of the appearance of excellent tissue response to CPC. CPC(citric) and CPC(acrylic) set quickly, similar to aw-FSCPC(chi), but the former two stopped their transformation to apatitic minerals. The c-CPC, which required a long setting time, was found to be crumbled, but the other CPCs maintained the shape at implantation. The aw-FSCPC(chi) and CPC(citric) showed no inflammatory response whereas c-CPC and CPC(acrylic) showed an inflammatory response one week after implantation. A component of the aw-FSCPC(chi) and c-CPC was an apatitic mineral whereas CPC(citric) and CPC(acrylic) showed no transformation to apatite. We concluded that the non-crumbling property plays a more dominant role in the appearance of excellent tissue response to CPC than the transformation to apatite. Also, a non-crumbling property is not a sufficient condition, but a necessary condition for the appearance of the excellent tissue response to CPC.