Toshiki Miyazaki

Review Paper: Behavior of Ceramic Biomaterials Derived from Tricalcium Phosphate in Physiological Condition

Various calcium phosphates are used for bone repair. Although hydroxyapatite (HA) sintered ceramics are widely used due to their osteoconductivity, its bioresorbability is so low that HA remains in the body for a long time after implantation. In contrast, tricalcium phosphate (TCP) ceramics show resorbable characters during bone regeneration, and can be completely substituted for the bone tissue after stimulation of bone formation. Therefore, much attention is paid to TCP ceramics for scaffold materials for supporting bone regeneration. This paper reviews bioresorbable properties of calcium phosphate ceramics derived from β-TCP and α-TCP.

Mechanism of bonelike apatite formation on bioactive tantalum metal in a simulated body fluid

Development of tantalum metal with bone-bonding ability is paid much attention because of its attractive features such as high fracture toughness, high workability and its achievement on clinical usage. Formation of bonelike apatite is an essential prerequisite for artificial materials to make direct bond to living bone. The apatite formation can be assessed in vitro using a simulated body fluid (SBF) that has almost equal compositions of inorganic ions to human blood plasma. The present authors previously showed that the apatite formation on tantalum metal in SBF was remarkably accelerated by treatment with NaOH aqueous solution and subsequent firing at 300 degrees C, while untreated tantalum metal spontaneously forms the apatite after a long soaking period. The purpose of the present study is to clarify the reason why the NaOH and heat treatments accelerate the apatite formation on tantalum metal. X-ray photoelectron spectroscopy was used to analyze changes in surface structure of the tantalum metal at an initial stage after immersion in SBF. Untreated tantalum metal had tantalum oxide passive layer on its surface, while amorphous sodium tantalate was formed on the surface of the tantalum metal by the NaOH and heat treatments. After soaking in SBF, the untreated tantalum metal sluggishly formed small amount of Ta-OH groups by a hydration of the tantalum oxide passive layer on its surface. In contrast, the treated tantalum metal rapidly formed Ta-OH groups by exchange of Na+ ion in the amorphous sodium tantalate on its surface with H3O+ ion in SBF. Both the formed Ta-OH groups combined with Ca2+ ion to form a kind of calcium tantalate, and then with phosphate ion, followed by combination with large amount of Ca2+ ions and phosphate ions to build up apatite layer. The formation rate of Ta-OH groups on the treated tantalum metal predominates the following process including adsorption of Ca2+ ion and phosphate ion on the surface. It is concluded that the acceleration of the apatite nucleation on the tantalum metal in SBF by the NaOH and heat treatments was attributed to the fast formation of Ta-OH group, followed by combination of the Ta-OH groups with Ca2+ and phosphate ions.

Bonding of alkali- and heat-treated tantalum implants to bone.

Alkali- and heat-treated tantalum (Ta) has been shown to bond to bone. The purpose of this study was to investigate the effects of chemical treatments on the bone-bonding ability of tantalum implants in rabbit tibiae. Miyazaki et al. reported in vitro that alkali- and heat-treated tantalum had an apatite forming ability in an acellular simulated body fluid (SBF). In this study, smooth-surfaced rectangular plates (15 x 10 x 2 mm) of pure tantalum and treated tantalum were prepared. The plates were implanted transcortically into the proximal metaphyses of bilateral rabbit tibiae, alkali- and heat-treated plates for one limb and untreated plates for the contralateral limb, which served as a paired control. Bone bonding at the bone/implant interface was evaluated by tensile testing and undecalcified histological examination, at 8 and 16 weeks after implantation. The treated implants showed weak bonding to bone at 8 weeks, and exhibited significantly higher tensile failure loads compared with untreated tantalum implants at 16 weeks. The untreated implants showed almost no bonding, even at 16 weeks. Histological examination by Giemsa surface staining, contact microradiography (CMR), and scanning electron microscopy (SEM) revealed that treated tantalum implants bonded directly to bone tissue. In contrast, the untreated tantalum implants had a intervening fibrous tissue layer between the bone and the plate and did not bond to bone at 8 and 16 weeks. It is clear from these results that alkali and heat treatment induce the bone-bonding ability of tantalum. This new bioactive tantalum should be an effective material for weight-bearing and bone-bonding orthopedic devices.

Apatite deposition on polyamide films containing carboxyl group in a biomimetic solution

The development of organic–inorganic hybrids composed of hydroxyapatite and organic polymers is attractive because of their novelty in being materials that show a bone-bonding ability, i.e. bioactivity, and because they have mechanical properties similar to those of natural bone. The biomimetic process has received much attention for fabricating such a hybrid, where bone-like apatite is deposited under ambient conditions on polymer substrates in a simulated body fluid (SBF) having ion concentrations nearly equal to those of human extracellular fluid or related solutions. It has been shown that the carboxyl group is effective for inducing heterogeneous nucleation of apatite in the body. In the present study, apatite deposition on polyamide films containing various numbers of carboxyl groups was investigated in 1.5 SBF, which had ion concentrations 1.5 times those of a normal SBF. The effect of incorporation of calcium chloride on the formation of apatite was examined. Polyamide films containing ≤33 mol % CaCl2 did not form apatite, even after soaking in 1.5 SBF for 7 days, and even when the polymer film contained 50 mol % carboxyl group. On the other hand, those modified with ≥40 mass % CaCl2 formed apatite on their surfaces in 1.5 SBF. The ability of the modified film to form an apatite layer increased, and the adhesion of the apatite layer bonded to the film improved, with increasing carboxyl group content. It is concluded that novel apatite–polyamide hybrids can be prepared by a biomimetic process.

Bioactive ceramic-based materials with designed reactivity for bone tissue regeneration

Bioactive ceramics have been used clinically to repair bone defects owing to their biological affinity to living bone; i.e. the capability of direct bonding to living bone, their so-called bioactivity. However, currently available bioactive ceramics do not satisfy every clinical application. Therefore, the development of novel design of bioactive materials is necessary. Bioactive ceramics show osteoconduction by formation of biologically active bone-like apatite through chemical reaction of the ceramic surface with surrounding body fluid. Hence, the control of their chemical reactivity in body fluid is essential to developing novel bioactive materials as well as biodegradable materials. This paper reviews novel bioactive materials designed based on chemical reactivity in body fluid.

Bioactive tantalum metal prepared by NaOH treatment

Untreated tantalum metal formed an apatite on its surface in simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma. However, it took an induction period as long as 4 weeks for apatite formation. The tantalum metal formed the apatite within 1 week when it was previously soaked in a 0.2 or 0.5M NaOH aqueous solution at 60 degrees C for 24 h to form a sodium tantalate hydrogel layer on its surface. The decrease in the induction period of apatite formation was attributed to the catalytic effect of the Ta-OH groups on the surface of the tantalum metal for apatite nucleation and acceleration of the apatite nucleation by an increased ionic activity product of the apatite in the fluid due to the release of Na(+) ions. The NaOH-treated tantalum metal can form apatite in a short period even in the living body and bond to the bone through this apatite layer. This indicates that a highly bioactive tantalum metal can be obtained by a simple chemical treatment.

Induction and Acceleration of Bonelike Apatite Formation on Tantalum Oxide Gel in Simulated Body Fluid

Untreated tantalum metal forms bonelike apatite layer on its surface in a simulated body fluid (SBF) after a long period. The apatite formation on the tantalum metal is significantly accelerated, when the metal was previously subjected to NaOH and heat treatments to form an amorphous sodium tantalate on its surface. The fast formation of the apatite on the NaOH- and heat-treated tantalum metal was explained as follows. The sodium tantalate on the surface of the metal releases the Na+ ion via exchange with H3O+ ion in SBF to form a lot of Ta-OH groups on its surface. Thus formed Ta-OH groups induce the apatite nucleation and the released Na+ ion accelerates the apatite nucleation by increasing ionic activity product of the apatite in SBF due to increase in OH− ion concentration. In the present study, in order to confirm this explanation, apatite formations on sodium tantalate gels with different Na/Ta atomic ratios, which were prepared by a sol-gel method were investigated. It was found that even Na2O-free tantalum oxide gel forms the apatite on its surface in SBF. This proves that the Ta-OH groups abundant on the gel can induce the apatite nucleation. The apatite-forming ability of the gels increased with increasing Na/Ta atomic ratios of the gels. The sodium-containing tantalum oxide gels released the Na+ ion, the amount of which increased with increasing Na/Ta atomic ratios of the gels. The released Na+ ion gave an increase in pH of SBF. These results prove that the apatite nucleation induced by the Ta-OH groups is accelerated with the released Na+ ion by increasing ionic activity product of the apatite in SBF.

Heterogeneous nucleation of hydroxyapatite on protein: structural effect of silk sericin

Acidic proteins play an important role during mineral formation in biological systems, but the mechanism of mineral formation is far from understood. In this paper, we report on the relationship between the structure of a protein and hydroxyapatite deposition under biomimetic conditions. Sericin, a type of silk protein, was adopted as a suitable protein for studying structural effect on hydroxyapatite deposition, since it forms a hydroxyapatite layer on its surface in a metastable calcium phosphate solution, and its structure has been reported. Sericin effectively induced hydroxyapatite nucleation when it has high molecular weight and a β sheet structure. This indicates that the specific structure of a protein can effectively induce heterogeneous nucleation of hydroxyapatite in a biomimetic solution, i.e. a metastable calcium phosphate solution. This finding is useful in understanding biomineralization, as well as for the design of organic polymers that can effectively induce hydroxyapatite nucleation.

Ceramic–metal and ceramic–polymer composites prepared by a biomimetic process

A biomimetic process was developed to prepare apatite–metal and apatite–polymer composites. A variety of metals and organic polymers incorporated surface functional groups such as Si–OH, Ti–OH or Ta–OH to induce formation of a biologically active bonelike apatite by chemical treatment or physical adsorption. Subsequent immersion in a simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma or 1.5 SBF led to the formation of a dense and uniform bonelike apatite layer on the surface. Apatite–metal and apatite–polymer composites prepared in this way are believed to be very useful as artificial bone substitutes.

Bone formation on apatite-coated titanium with incorporated BMP-2/heparin in vivo

OBJECTIVE The objective of this study was to investigate whether the in vivo osteoinductive activity of an implant material is enhanced by covering the surface of apatite with incorporated bone morphogenetic protein 2 (BMP-2) and heparin which maintains the activity of BMP-2. STUDY DESIGN Titanium implants were alkaline treated, heat activated, and soaked in stimulated body fluid with or without BMP-2/heparin to coat the apatite around them. Treated implant bars were then implanted in rat tibiae. After 3 weeks, nondecalcified sections were prepared and the new bone formation around the implants was examined. RESULTS A greater amount of bone formed on the apatite-coated implants containing BMP-2/heparin than on apatite-coated implants containing BMP, with >or=3 microg/mL heparin. Apatite-coated titanium implants with BMP-2/heparin had significantly enhanced new endosteal bone formation, with increases vertically (134%) and horizontally (124%). CONCLUSIONS Bone formation was stimulated around the apatite-covered titanium coated with BMP-2/heparin, which may be useful in improving implant therapy.