Living hard tissue replacement, its preparation, and preparation of integral body

Abstract: A living hard tissue replacement is prepared by superplastic forming a ceramic material which contains CaO, SiO₂, and MgO, is substantially free of calcium phosphate, but capable of forming a calcium phosphate base compound upon contact with phosphorus-containing water. A replacement is also prepared by superplastic forming a sintered composite body comprising a calcium phosphate base ceramic matrix and an inorganic filler dispersed therein. Both the replacements are suitable as artificial dental roots and crowns.

Description: This invention relates to a method for preparing living hard tissue replacements. BACKGROUND OF THE INVENTION A variety of filling and repairing materials have been utilized to restore the function and configuration of a deficient part of a living body. Typical filling and repairing materials for living bodies include artificial bones and analogues such as artificial dental roots and crowns as well as artificial joints. They are generally known as living hard tissue replacements. These living hard tissue replacements are required to be mechanically strong, tough, and stable in living bodies and should have high affinity to living bodies. Another important factor is ease of shaping because a living hard tissue replacement has to be a custom-made part conforming to an individual patient's deficient site. The biological affinity used in this context means how a living hard tissue replacement adapts itself to and merges or assimilates with the surrounding living tissue where the replacement is embedded or implanted. Thus, a material having high biological affinity is scarcely recognized as xenobiotic by the surrounding tissue. Particularly when such material is used as an artificial bone, it can promote osteogenesis from the surrounding bone to eventually form a firm bond between itself and the bone tissue. Among the currently available artificial bone materials, those featuring high mechanical strength and in vivo stability are metals such as titanium and zirconium, alloys containing such metals, and ceramics such as alumina, silicon nitride, and zirconia. The materials having high mechanical strength and in vivo stability, however, have low biological affinity, that is, are unlikely to assimilate with living tissue, resulting in an extended cure time and poor adherence to the living tissue. In addition, they have to be extracted and removed by surgical operations after they have performed their duties. Typical of known materials having high biological affinity are bioglass, apatite (especially hydroxyapatite), tricalcium phosphate, and calcium phosphate crystallized glass. Apatite has the best biological affinity as understood from the fact that bone is essentially composed of apatite if organic components are excluded. These materials having high biological affinity have low mechanical strength and toughness. Since normally a pressure of about 30 kg/cm² and sometimes a maximum pressure of about 300 kg/cm² is applied to the dental root during mastication, artificial dental roots of apatite seem unreliable in durability. We discovered that among ceramic materials which contain CaO and SiO₂ as essential components and optionally MgO, diopside, wollastonite and analogues, upon contact with body fluids, form a calcium phosphate base compound at the contact area so that these materials exhibit improved biological affinity, especially biological activity although they are non-calcium phosphate ceramics. This is the subject matter of our preceding application, Japanese Patent Application No. 142058/1989 filed June 6, 1989 (USSN filed June 6, 1990 or EPA 0401793.9 filed June 6, 1990). These ceramic materials are suitable as living hard tissue replacements since they can compensate for the mechanical strength and toughness calcium phosphate base ceramic materials lack, without detracting from the biological affinity characteristic of calcium phosphate base ceramic materials. In our preceding application, the ceramic materials are sintered at a temperature of 1,100 to 1,550°C into a sintered body. In one preferred embodiment, the sintered body is pulverlized into a powder which is applied and joined to a substrate by spray coating, solvent welding, solution coating, or sputtering. To obtain a living hard tissue replacement having a complex profile, the sintered body has to be machined with difficulty. The preferred embodiment in which the ceramic material is bonded to a substrate has some likelihood that exfoliation can occur at the interface during repetitive use, indicating that the bonding force is less satisfactory. There are additional problems that the coating thickness is less uniform and shaping to a complex configuration is difficult. It was believed in the prior art that ceramics can be shaped only by sintering. However, like metals, attempts have been made to subject ceramics to plastic forming, for example, by forging, extruding and rolling. For the plastic forming of ceramics, it is necessary to heat the material to a temperature higher than its melting point by about 60% or more, and the heating temperature can reach 2,000°C for a certain material. Nevertheless, those ceramic materials having superplasticity show extremely greater ductility, sometimes 10 times greater ductility, under low stresses at a temperature substantially lower, e.g., by 500°C, than the sintering or forging temperature as described in the literature, for example, Journal of the JSTP, 29, 326 (March 1988); Ceramics, 24, 2 (1989); and Tetsu to Hagane (Iron and Steel), 75, 3 (1989). Typical prior art ceramic materials known to show superplastic nature are Y-TZP (yttria-stabilized tetragonal ZrO₂ polycrystals) and ZrO₂-Al₂O₃ systems. To take advantage of plastic deformation, extrusion molding and thin plate molding have been attempted on them. Attempts have also been made to diffusion bond two pieces of the same material by superplastic forming. We have discovered that calcium phosphate base ceramic materials including apatite and tricalcium phosphate show superplastic nature. This is the subject matter of our application, Japanese Patent Application No. 155758/1989 filed June 20, 1989. However, no study has been made on the superplasticity of diopside. We have discovered that a superplastic phenomenon also develops with non-calcium phosphate base ceramic materials such as diopside. SUMMARY OF THE INVENTION For the purpose of improving the generally low mechanical strength and toughness of biologically active ceramic materials, especially living hard tissue replacements of calcium phosphate base ceramic materials, we have selected as candidate a ceramic material which contains CaO and SiO₂ as essential components and can form a calcium phosphate compound upon contact with a phosphorus-containing aqueous fluid in a living body. Therefore, an object of the present invention is to provide a method for preparing a novel and improved living hard tissue replacement which can be readily formed to the desired shape, surface nature, and dimensions in conformity to an individual patient. The present invention provides a living hard tissue replacement prepared by the superplastic forming of a ceramic material which contains CaO and SiO₂ as essential components, is substantially free from calcium phosphate, but capable of forming a calcium phosphate base compound upon contact with a phosphorus-containing aqueous solution. The invention also provides a method for preparing a living hard tissue replacement comprising the step of superplastic forming the ceramic material defined above. Most often, the ceramic material further contains MgO and the ceramic material belongs to the diopside, wollastonite, akermanite, monticellite, alite, or belite field. The living hard tissue replacement is most often used as an artificial dental root or crown. BRIEF DESCRIPTION OF THE DRAWINGS The above and other objects, features, and advantages of the present invention will be better understood from the following description taken in conjunction with the accompanying drawings, in which: FIGS. 1 to 3 are perspective views illustrating steps of the method for preparing an integrated body as a living hard tissue replacement according to the invention; FIG. 4 is a cross-sectional view of a dental root implanted in an alveolar bone, the root having a crown cemented thereto; and FIG. 5 is a phase diagram of a CaO-MgO-SiO₂ ceramic system. DETAILED DESCRIPTION OF THE INVENTION The invention uses a non-calcium phosphate ceramic material which contains CaO and SiO₂ as essential components and can form a calcium phosphate base compound upon contact with a phosphorus-containing aqueous solution. It has never been reported that ceramic materials prepared according to the present invention containing CaO and SiO₂ as essential components have superplastic nature. The ceramic materials containing CaO and SiO₂ as essential components and substantially free of calcium phosphate preferably contain CaO and SiO₂ in a weight ratio of from 1:4 to 6:1, more preferably from 1:3 to 2:1. Strength and biological affinity become less desirable outside the range. The ceramic materials may further contain MgO in an amount of up to 35% by weight based on the total weight of the material. Inclusion of MgO has the advantages of lower sintering temperatures and improved adhesion to bones. The ceramic materials prepared according to the present invention contain calcium oxide and silicon dioxide as essential components are generally composed of 10 to 90%, especially 7 to 77% by weight of CaO, 10 to 80%, especially 23 to 70% by weight of SiO₂, and 0 to 35% by weight of MgO based on the total weight. The preferred composition is 7 to 65% by weight of CaO, 40 to 70% by weight of SiO₂, and 0 to 35% by weight of MgO. Better results are obtained when the ceramic composition is composed of 7 to 40% by weight of CaO, 45 to 70% by weight of SiO₂, and 8 to 35% by weight of MgO. The ceramic materials used in the present invention are characterized in that upon contact with an aqueous solution containing phosphorus, for instance, spurious and true body fluids, they form calcium phosphate base compounds, typically hydroxyapatite on their surfaces of contact. This characteristic feature ensures that when they are implanted in a living system, an amorphous calcium phosphate base compound with satisfactory biological affinity uniformly and rapidly precipitates on their surfaces of contact with living bones, so promoting the formation of neoblastic bones. In addition, the thus formed junctions with living bones are very firm since the junctions have a graded concentration of composition with crystallographical continuity established between the implants and the living bones. The ceramic materials used herein generally have a composition belonging to the fields of diopside CaO·2SiO₂·MgO, wollastonite CaO·SiO₂, alite 3CaO·SiO₂, belite 2CaO·SiO₂, akermanite 2CaO·2SiO₂·MgO, montecellite CaO·SiO₂·MgO, forsterite, proteoenstatite, tridymite and so on. Among others, preference is given to diopside, wollastonite, alite, belite, akermanite, and monticellite. The most preference is given to ceramic materials predominantly comprising diopside and wollastonite compositions and having relatively low sintering temperatures of 1,200 to 1,350°C because of their high biological affinity. In particular, ceramic materials containing diopside components, especially those having a composition belonging to the diopside field have high flexural strength and biological affinity. FIG. 5 is a phase diagram of a CaO-MgO-SiO₂ system in which the diopside, wollastonite, and other fields are delimited. Preferably, the phases of diopside and wollastonite, particularly that of diopside, occupy at least 40% by volume, especially at least 50% by volume, more especially 70 to 100% by volume of ceramic materials. The quantity of such phases contained in ceramics may be determined by X-ray powder diffraction methods. The ceramic materials used herein are generally prepared by mixing together calcium oxide, silicon oxide, and optionally magnesium oxide in a predetermined proportion, calcining or pre-sintering the mixture, pulverizing the calcined product, and then sintering the powder again. In place of the oxides, use may be made of substances capable of producing such oxides under sintering conditions such as carbonates, bicarbonates, and hydroxides of calcium and magnesium and silicic acid. Such stock materials may be used not only in powder or granular form, but also in slurry or solution form. Instead of the stock materials corresponding to the respective components, use may also be made of preformed diopside CaO·2SiO₂·MgO or compositions belonging to the diopside field after pulverizing them into powder. Alternatively, use may be made of mixtures of diopside with other analogous substances such as wollastonite, forsterite, akermanite, proteoenstatite, tridymite, and belite. Such analogous substances are obtained as by-products during preparation of ceramic materials whose composition belongs to the diopside field if any one of calcium, magnesium and silicon oxide feed stocks is used in excess. It is acceptable to blend additives to the ceramic materials such that there may be present P₂O₅, TiO₂, Al₂O₃, Na₂O, K₂O, and B₂O₃ in a total amount of up to 5% by weight. The ceramic materials are prepared from such stock materials by pulverlizing the stock materials into powders and mixing them together in a mixing machine such as a ball mill, vibratory mill, automatic mortar, mixer, juicer, sand mill and whipping unit. The mixture is then dried at 50 to 300°C for 10 minutes to 100 hours and calcined or presintered at 500 to 1,600°C, preferably 800 to 1,600°C for 10 minutes to 200 hours. The calcined product is pulverized and molded into a compact of desired shape by pressing, slip casting, etc., while a binder such as polyvinyl alcohol is added if required. The compact is dried and finally sintered at a temperature of from 800 to 1,700°C, preferably from 900 to 1,600°C. In this procedure, the powders of stock materials should have a particle size corresponding to a BET value of usually at least 0.5 m²/g, preferably at least 1 m²/g, more preferably at least 3 m²/g. The molding pressure ranges from 1 to 3,000 kg/cm². The sintering time usually ranges from 10 minutes to 20 hours. Sintering is usually carried out under atmospheric pressure, but under an increased pressure in the range of from 10 to 3,000 kg/cm² if required. The ceramic materials resulting from sintering preferably have an average grain size of up to 10 µm, more preferably from 0.005 to 1 µm and a relative density of at least about 70%, more preferably at least 90%, most preferably at least 99.5%. Then the ceramic materials develop a superplastic phenomenon at a temperature in the range of from 800 to 1,600°C. It is to be noted that the average grain size may be measured by means of a scanning electron microscope (SEM) by determining an average grain area, and determining the average diameter of a phantom circle having the average grain area. The average diameter is the average grain size. During sintering, concurrent hot pressing (HP) or hot isostatic pressing (HIP) is preferably carried out for densification purposes. The sintering atmosphere may be an inert gas, air, hydrogen or vacuum. The compact may be calcined or pre-sintered at at temperature of 50 to 300°C for about 3 minutes to about 30 hours before it is sintered. Whiskers may be contained in the sintered body for the purpose of increasing mechanical strength insofar as superplasticity is not detrimentally affected. The sintered body may take the form of a porous body having independent and interconnected cells. Since the ceramic materials of the invention have higher strength than the conventional calcium phosphate base materials, such a porous body can be produced so as to have any desired pore diameter and porosity while maintaining high biological affinity. The porous body generally has a pore diameter of 5 to 2,000 µm, preferably 10 to 1,000 µm and a porosity of 10 to 80%, preferably 20 to 70%, more preferably 25 to 60%. The porous body may be prepared according to well-known methods for the manufacture of porous ceramics, by mixing the stock material mixture with a pyrolytic substance or organic fibers, followed by sintering. The thus sintered porous body usually has a compression strength of at least 7 MPa, preferably at least 10 MPa, more preferably at least 15 MPa. The ceramic materials thus obtained may be used either as blocks of the required shape or in the form of granules suitable for filling in bone defects. According to the present invention, the calcium oxide and silicon oxide-containing, non-calcium phosphate ceramic material is processed by superplastic forming. For brevity's sake, the materials are often referred to as sintered ceramic materials hereinafter. The forming temperature ranges from 500°C to a temperature lower than the sintering temperature, preferably lower by 50°C. More illustratively, the temperature ranges from 600 to 1,600°C, often from 600 to 1,300°C, most often from 800 to 1,200°C. The superplastic forming uses a mold with a cavity having the shape and dimensions corresponding to the intended living hard tissue replacement or implant and is performed by subjecting the sintered ceramic material to extrusion shaping or embossing. During the process, both the sintered ceramic material and the mold should be heated to a temperature at which the sintered material exhibits superplasticity. The sintered ceramic material subject to superplastic forming is preferably in the form of thin plates or sheets, granules, and powder particles. Superplastic forming causes thin sheets or granules to fuse together to form a continuous crystalline structure at their interface, resulting in a very firm junction. The compression rate, compression force, and deformation during superplastic forming vary with a particular technique employed. Preferred forming parameters include a compression rate of 0.01 to 50 mm/min., a compression force of 1 to 2,000 MPa, more preferably 1 to 500 MPa, especially 1 to 100 MPa, and a deformation of about 0.1 to about 1.5 in true strain. In the case of embossing, the sintered ceramic material which has been shaped to approximately the desired configuration, for example, the dental crown shape may be used. In this case, only a minimal deformation is to be achieved by superplastic forming or embossing, with the benefit of ease of forming. The superplastic forming may also be carried out by rolling, drawing, tubing, bending, shearing, deep drawing, and other pressing techniques as well as a hot pressing technique using a mold or a hot isostatic pressing (HIP) technique. Further, the superplastic forming may be repeated any times if desired. In general, the thus formed ceramic material has experienced a change in grain size as low as 100% or less. It is sometimes observed that the grains have undergone slippage along the grain boundary, deformation, and orientation. In one preferred embodiment of the present invention, a sintered ceramic material as previously described and a material of the same or different type are joined together by superplastic forming. More particularly, the two materials are placed in pressure contact to provide a diffusion or solid phase bond. Pressure contact may be achieved between a sintered ceramic material and a substrate of a different material by pressing the stacked materials in close contact using a press or punch or by extruding or reverse extruding the sintered ceramic material through a die using a punch formed of the substrate material. Pressure contact may also be accomplished by rolling and drawing combined with extrusion. The superplastic forming may be repeated any times if desired. The superplastic forming joins and shapes the sintered ceramic material and the heterogeneous material together into an integral body having a bond strength as high as 30 to 1,000 MPa, especially 100 to 1,000 MPa although the bond strength depends on the type of the heterogeneous material. The material of different type to be joined is not particularly limited. It may be selected from various ceramic materials, various metals, various glasses, composites thereof, and other suitable materials. The material to be joined may or may not exhibit plastic deformation during pressure joining. Also, it may or may not exhibit superplastic deformation. If the material to be joined has superplastic nature, then it is possible to join three or more materials together at the same time. Most often, the material to be joined has high mechanical strength and functions as a substrate or support. In the preferred embodiment wherein the sintered ceramic material covers a substrate of different material, two materials are held in close contact at a predetermined temperature and pressure by hot isostatic pressing (HIP), thereby achieving a diffusion or solid phase bond therebetween. The sintered ceramic material as the cover layer undergoes superplastic deformation during the HIP process. For the HIP process, the temperature generally ranges from 500°C to lower than the sintering temperature, usually from 500°C to 1,600°C. The compression force generally ranges from 1 to 2,000 MPa, usually from 1 to 500 MPa. The heating/pressing time may vary over a wide range of from about 6 seconds to 25 hours. The deformation ranges from about 0.1 to about 1.5 in true strain. Referring to FIGS. 1 to 3, an assembly of a substrate and a cover is shown in perspective views to illustrate the method for preparing an integral body using the HIP process. The elements involved in this method are a substrate 11, a cover 12 formed of superplastic ceramic material, a surrounding/pressurizing medium 23 in the form of ceramic powder, and an enclosure 24 in the form of a glass envelope for enclosing the foregoing three elements in a stationary manner. The substrate 11 is preferably formed of a material which can withstand repetitive stresses and has a flexural strength of 200 MPa or higher, sometimes as high as 1500 MPa and a high melting point of 700°C or higher. Also preferably, the substrate material undergoes little deformation, say, a deformation of less than 10%, during superplastic HIP joining. Preferred examples of the substrate material include metals and ceramics, which should be safe to living bodies in the case of living hard tissue replacements. The substrate-forming metals include elemental metals such as Ti, W, Mo, Au, and Pt and alloys such as Ni-Cr, Ni-Ti, Fe-Cr-Al, Ti-Zr, Fe-Ni-Cr, Ti-Al-V, Co-Cr, Co-Cr-Mo, Ti-Mo, and stainless steel. The metal substrate is preferably pretreated on their surface. For example, the substrate surface is roughened by blasting with #20 to #400 steel shots or etching. Similar results are obtained when a metal of the same type as the substrate is sprayed to the substrate surface by plasma or gas spraying techniques. The rough surface of the substrate resulting from any of the foregoing treatments may be further treated with a corrosive inorganic or organic acid much as hydrochloric acid, sulfuric acid, nitric acid and oxalic acid by coating or immersion and then heat treated at a temperature of 300 to 1,000°C for one to two hours, forming an oxide on the rough surface of the metal substrate. Surface roughening optionally followed by oxide formation has the advantage that a closer contact and hence, a higher bonding force is established between the substrate and the cover because the substrate and the cover are microscopically interdigitated at their interface during joining by HIP The ceramics useful as the substrate 11 include high strength ceramics such as zirconia, SiC, SiN, BN, and Al₂O₃. The cover 12 is of a superplastic ceramic material which is selected from biologically active ceramic materials including calcium oxide and silicon oxide-containing, non-calcium phosphate ceramic materials and calcium phosphate/filler composite materials as previously described. More particularly, the cover 12 is formed from a sintered ceramic material having a predetermined grain size. The configuration and dimensions of the cover 12 may be determined in accordance with the configuration and dimensions of the substrate 11. The sintered ceramic material of which the cover 12 is made may have a grain size one to ten times the desired grain size in the final product. It is desired that the difference in thermal expansion coefficient between the substrate 11 and the cover 12 be within 50%, preferably within 40%, more preferably within 10%. The ceramic powder used as the surrounding/pressurizing medium 23 includes zirconia, alumina, BN, SiC, SiN, WC, and partially stabilized zirconia although high temperature ceramics which do not melt at the superplastic forming temperature involved in the HIP process, especially at 700°C or higher temperatures are preferred. A proper choice should be made of the particle size of the ceramic powder 23 since the cover 12 joined to the substrate by superplastic forming can have a surface roughness corresponding to the selected particle size of the surrounding powder. Therefore, the ceramic powder may have a particle size of about 10 to about 500 µm. The ceramic powder layer 23 is generally about 0.5 mm to about 50 mm thick. The glass envelope 24 may be formed of silica glass, boron oxide glass, silicate glass, borosilicate glass, germanate glass, phosphate glass or the like. It is generally about 100 µm to about 5,000 µm thick. These elements are assembled as follows. First, a suitable support material is shaped and finished to form a substrate or support 11 of predetermined configuration and dimensions depending on the intended use. Separately a ceramic material is sintered to form a hollow cylindrical cover or sleeve 12. The cover or sleeve 12 generally has a wall thickness of up to 10 mm, preferably 10 µm to 3 mm. Then the substrate 11 is fitted and received in the cover 12 as shown in FIG. 1. Preferably the substrate 11 is snugly fitted in the cover 12 with the gap therebetween being as small as 0.3 mm or less. The substrate 11 has substantially the same configuration as the final product. More particularly, the substrate 11 may be provided with grooves, recesses, ridges, or rims on its surface if desired. In the illustrated example, the substrate 11 is a cylinder formed with a circumferential groove at an axial intermediate. The configured substrate 11 may be prepared by sintering, casting, and/or machining. Also, the cover 12 has substantially the same outer configuration as the final product. However, the cover 12 may take a simple configuration having a smooth outer surface while necessary surface irregularities can be omitted at this point. This leads to efficient manufacture because only the substrate 11 need precise shaping and the cover 12 can have a simple configuration. The simple configuration allows the cover to be formed to a uniform wall thickness, resulting in the final coating with a uniform thickness. Instead of prefabricating a cover of a sintered ceramic material, it is also contemplated herein to apply a sintered ceramic material to a substrate and subject the coated substrate to superplastic forming. The sintered ceramic material can be applied to the substrate by any well-known coating methods including spray coating, welding, solution coating, and sputtering. The spray coating often relies on a plasma or gas and uses a coating material having a particle size of #50 to #500. A material with a particle size of less than #50 does not smoothly flow during spray coating whereas particles of larger than #500 are difficult to deposit. The welding method is by mixing together the ceramic material and glass both serving as coating materials in the presence of water to form a paste, coating and sintering the paste to the substrate. The sintering temperature is higher than the softening temperature of glass, usually 400 to 1,000°C. The glass used may be selected from silica, borate, silicate, borosilicate and phosphate glasses, with the borosilicate glass being preferred because of appropriate welding temperature. The amount of glass blended is 5 to 80% by weight, preferably 15 to 60% by weight based on the total weight of the coating material. With less than 5% by weight of glass, the coating material would not firmly adhere to the substrate. More than 80% by weight of glass adversely affects biological affinity. In the case of solution coating, the coating material is dissolved to saturation in a medium such as hydrochloric acid, sulfuric acid, and nitric acid. The solution is applied to the substrate by coating or dipping and then heated to a temperature of at least 300°C in an inert gas. Heating temperatures of lower than 300°C are too low to provide a bond whereas temperatures of higher than 1,000°C would deteriorate certain substrate materials, imposing limitation on the substrate material. Sputtering is carried out by mounting a target of coating material in a sputtering device, effecting presputtering for a certain time, usually for 5 to 60 minutes, then heating the substrate to a temperature of about 20 to 500°C, and effecting substantial sputtering. The sputtering times depends on the desired film thickness. After sputtering, the coated substrate is often post treated at 100 to 1,300°C. Next, the assembly of substrate 11 fitted in cover 12 in the former embodiment or the coated substrate 11 in the latter embodiment is covered with ceramic powder 23 and enclosed in the glass envelope 24 as shown in FIG. 2. The envelope is then loaded in a conventional HIP apparatus which applies heat and pressure to the envelope, creating a strong junction between substrate 11 and cover 12. There results an integral or composite body 1 in which a coat 15 is closely bonded to the substrate 11 as shown in FIG. 3. At the end of HIP forming, the glass envelope 24 is broken and the integral body 1 is taken out. During the HIP process, the substrate 11 is little deformed and the coat 15 of uniform thickness closely conforms to the outer contour of substrate 11. The isostatic pressing minimizes the chance of poor bond. The coat 15 on the formed composite body 1 generally has a thickness of from about 1 µm to about 10 mm, preferably from 1 µm to 5 mm, more preferably from 10 µm to 3 mm. The coat 15 does not peel away even when it is relatively thick as several millimeters. The coat 15 can be finished to a mirror or rough surface through a proper choice of the particle size of the surrounding ceramic powder 23. For increased surface area and biological activity, the coat should have a rough surface having a surface roughness Rmax of about 10 to about 500 µm. The superplastic junction using an HIP process has been described. In the practice of the invention, a hot pressing (HP) process may also be used to establish a junction insofar as the substrate 11 having substantially the same configuration as the final composite body 1 can be combined with a cover 12 of a simple configuration capable of fitting over the substrate. The HP process involves the steps of engaging the substrate 11 with the cover 12 in place, embedding the assembly in the ceramic powder 23 in a press mold, and forcing a punch thereto. The press mold is preferably formed of the same or similar material as the ceramic powder. Then a bond is established to a degree substantially equal to the HIP process. The superplastic forming of a sintered ceramic material, which may be either a calcium oxide and silicon oxide-containing, non-calcium phosphate ceramic material results in a single body or a integrated body depending on whether or not the ceramic material is combined with a substrate, both the single and integrated bodies serving as living hard tissue replacements. The living hard tissue replacements may be utilized as parts at least partially embedded in a living body, for example, artificial dental parts such as dental roots and crowns, artificial bones (including general bones, skull, ossiculum auditus, jaw bone, cartilagines ansi, etc.), bone replacements, artificial joints, fracture fixtures, artificial valves, and artificial blood vessels as well as medical equipment, for example, hypodermic implanting equipment such as dialysis shunts, living body embedding equipment such as pacemakers, and other living body indwelling equipment. Now, the application of the integrally formed body of the invention to an artificial dental root and crown as a typical living hard tissue replacement is described. The artificial dental root and crown are preferably of the construction in which a sintered ceramic material is joined to the surface of a substrate by superplastic forming. FIG. 4 shows an artificial dental root and crown according to one preferred embodiment of the invention. An artificial dental root 3 to which a crown 4 is secured through a damping member 5 by cement layers 6 and 7 is implanted in an alveolar bone 71. The dental root 3 includes a root substrate 31 and a coat layer 35 bonded to the substrate surface. The root 3 on the outer surface is formed with a plurality of tabs or threads 33. The tabs 33 have an anchoring function and a function of defining gaps between the root 3 and the alveolar bone 71. The root 3 does not directly integrate with the surrounding alveolar bone 71, but a neoblastic bone which will form around the root. The provision of tabs 33 promotes the growth of a new bone, ensuring a firm bond between the root 3 and the alveolar bone 71. The shape of tabs 33 is not critical, and they may be circumferential rings, screw threads or discrete protuberances on the outer surface of the root 3. The tabs 33 are generally 100 µm to 3 mm in radial height. The configuration and dimensions of substrate 31 are not critical. The substrate may be configured to the shape and dimensions corresponding to the intended artificial dental root as previously described. It is preferably formed with tabs corresponding to the tabs 33. It is preferably formed from a safe material having high mechanical strength and toughness as previously described, inter alia, titanium, titanium alloy, zirconia, and monocrystalline alumina (sapphire). The coat layer 35 on the root substrate 31 is formed from a sintered ceramic material and joined to the substrate 31 by superplastic forming. The coat layer 35 is initially a hollow cylinder having one closed end and one open end formed from a sintered ceramic material and adapted to fit over the substrate 31. The cover cylinder is preferably about 10 µm to about 10 mm thick. The superplastic forming causes the cover cylinder of ceramic material to deform in conformity with the outer contour of substrate 11 and to bond to the substrate 11 without leaving a gap. The coat layer 35 of uniform thickness is joined to the substrate 11 in this way. The coat layer 35 preferably has a thickness of 1 µm to 5 mm, more preferably from 10 µm to 2 mm. The coat layer 35 should be present at least on those surface areas of the artificial dental root 3 which come in contact with a living body, for example, the alveolar bone 71, gingival epithelium 72, and subepithelial connective tissue 73 in FIG. 4. The artificial dental root 3 of the above-mentioned construction is not particularly limited in shape. A choice may be made of circular, oval, and rectangular column and blade shapes. It is preferred to provide tabs 33 as previously described. In general, the artificial dental root 3 has a maximum diameter of 2 to 20 mm and a height of 3 to 50 mm. It may be configured to any desired dimensions in accordance with various standards or to special dimensions if necessary. Although the artificial dental root 3 shown in FIG. 4 is a one-piece member, the invention is also applicable to two-piece dental roots having a post core and multiple-piece dental roots having three or more components. These roots should have a coat layer of ceramic material on at least the surface to be in contact with a living body. The dental crown 4 includes a coronal substrate 41 and a coat layer 45 bonded to the substrate surface. The coat layer 45 is formed of sintered ceramic material and joined to the coronal substrate 41 by superplastic forming. An initial cover which is fitted over the substrate and eventually converted into the coat layer 45 may have any appropriate thickness depending on the desired configuration and thickness of the coat layer. The configuration and dimensions of coronal substrate 41 are not critical. The coronal substrate 41 may be configured to a columnar or pyramid shape having a recess at its bottom for receiving the root or a combination of such shapes. The top side of the coronal substrate 41 may be flat, but preferably configured to a complex shape conforming to the intended crown. More particularly, the crown configuration largely differs between incisive and molar teeth. Thus, the use of a coronal substrate 41 configured to a shape conforming to a particular incisive or molar tooth leads to ease of forming because the sintered ceramic material requires minimal deformation. The material of which the coronal substrate 41 is formed may be selected from the same materials as previously mentioned for the root substrate. In order that the crown 4 have an aesthetic appearance similar to a natural tooth, biological affinity, and no detrimental influence to the gingival epithelium 72, the coat layer 45 should preferably surround the entire outer surface of the coronal substrate 41. The coat layer 45 generally has a thickness of about 1 µm to about 5 mm. The crown 4 illustrated in FIG. 4 is a single component crown although the present structure is applicable to the outer crown component of a two-component crown. The artificial dental crown 4 is secured to the artificial dental root 3 through the damping members 5 by cement layers 6 and 7 as shown in FIG. 4. The damping members 5 are effective for damping shocks applied to the root during mastication and gnash. Cementing of the crown to the root through the damping members allows the crown to fluctuate like a natural tooth. The damping members 5 are often formed of synthetic rubber to a thickness of about 0.01 to about 4 mm. The cement layers 6 and 7 may be of a conventional dental cement. The artificial dental root according to the invention is not only useful as an implant embedded in an alveolar bone when combined with the artificial crown as shown in FIG. 4, but also as an intradental implant by inserting the artificial root into a natural tooth. The artificial dental root combined with the artificial dental crown according to the invention is also useful in full and partial denture sets, and free-standing tooth replacements. The artificial dental root and crown according to the invention may be independently used in practice. That is, the artificial dental crown and root to be combined with the artificial dental root and crown according to the invention, respectively, need not have a coat layer of sintered ceramic material. The artificial dental root and crown according to the invention are effective even when they are combined with conventional artificial dental crown and root. EXAMPLE Examples of the present invention are given below by way of illustration and not by way of limitation. Example 1 Diopside having an average particle size of 1.0 µm was subjected to unidirectional pressing under a pressure of 300 kg/cm², and then to cold isostatic pressing (CIP) under a pressure of 2,000 kg/cm². It was then calcined for two hours at 1,000°C in air and then HIP sintered for two hours at 1,150°C and 2,000 kg/cm² in argon gas, obtaining a cylindrical sintered body. This cylindrical sintered body had a diameter of 4 mm, a height of 8 mm, a relative density of 99.9%, and an average grain size of 1.1 µm. The relative density was determined by measuring the density of a sintered sample by the Archimedian method. The sintered sample was pulverlized into powder having a surface area of 5 m²/g which was measured for true density. Relative density was calculated from the apparent and true densities. The average grain size was determined by means of a scanning electron microscope by determining an average grain area and determining the average diameter of a phantom circle having the average grain area. The sintered body had a flexural strength of 300 MPa and a fracture toughness of 3.5 MPam 1/2 . It is to be noted that flexural strength was determined by cutting out ten test specimens of 3 x 4 x 40 mm, mirror polishing them, and measuring by the three point bending test with a span of 36 mm and a cross head speed of 0.5 mm/min. Fracture toughness (KiC) was measured according to ASTM E399-83. The sintered body was subjected to forming in an inert gas atmosphere using an artificial dental root-shaped mold of molybdenum base alloy (TZM). The forming conditions included a holding temperature of 1,050°C, a compression rate of 1.0 mm/min., a compression force of 50 MPa, and a deformation of 0.5 in true strain. The forming resulted in an artificial dental root of diopside. It was observed at the end of forming that the average grain size was 1.0 µm and the grains had been distorted and oriented. Example 2 Diopside was subjected to unidirectional pressing under a pressure of 300 kg/cm², and then to cold isostatic pressing (CIP) under a pressure of 2,000 kg/cm². It was then calcined for two hours at 1,000°C in air and then HIP sintered for two hours at 1,150°C and 200 MPa in argon gas, obtaining a hollow cylindrical sintered body. It had a wall thickness of 1 mm, an inner diameter of 5.1 mm, and a height of 8 mm. It had an average grain size of 1.2 µm, a coefficient of thermal expansion of 12x10⁻⁶, a flexural strength of 300 MPa, and a fracture toughness (KiC) of 3.5 MPam 1/2 . A solid columnar piece of titanium (having a coefficient of thermal expansion of 8.4x10⁻¹²) serving as a root substrate was fitted in the hollow sintered cylinder as shown in FIG. 1. The titanium piece had a diameter of 5 mm, a height of 10 mm and a circumferential recess of 1 mm deep on the outer surface (see FIG. 1). The assembly was covered with BN ceramic powder having a high melting point (which does not melt at 700°C or higher) and an average particle size of 15 µm, and further enclosed in a silica glass envelope as shown in FIG. 2. Superplastic forming was effected by an HIP process under the conditions: a temperature of 1,100°C, a pressure of 30 MPa, and a time of 30 minutes. At the end of HIP forming, the glass envelope was broken and the BN powder was brushed off. There was obtained an artificial dental root having a diopside coat layer of 1 mm thick joined to the root substrate surface. The bond strength between the substrate and the coat layer was 100 MPa, as represented by the peel strength which was measured by withdrawing the root substrate from the joined root substrate-coat assembly secured in a jig. The coat layer had a surface roughness Rmax of 12 µm. The entire root had as high flexural strength and fracture toughness (KiC) as the Ti substrate. A biological affinity test was performed on the dental root sample of this Example. The dental roots were implanted in holes of 3 x 4 x 6 mm formed in the jaw bone of male adult rabbits weighing 2.5 to 2.8 kg. Polished, but non-decalsified specimens were prepared after the lapse of six weeks from the operation. An SEM photomicrograph was taken on the interface between the root and the newly grown bone. It was found that a biologically active interfacial film formed between the diopside implant and the bone and that the newly grown bone completely adhered to the root (implant) and penetrated and filled into pores therein, proving that the root had high biological affinity. A high resolution image was taken under a TEM on the interface between the artificial dental root and the matrix bone after 24 weeks. The sequence of bone cells was identical on both the root and matrix bone sides, with little or no distinct boundary observed therebetween. For comparison purposes, a junction was created by superplastic forming according to the same procedure as above except that the cover material was changed from diopside to hydroxyapatite (HAP) and the HIP superplastic forming temperature was 1,000°C. Although the HAP coat could be joined to the Ti substrate, the HAP coat which was less stress resistant was broken by the application of repetitive stresses. Example 3 The same substrate-coat assembly as in Example 2 was placed in a mold of SiC ceramic. The space between the assembly and the mold was charged with SiC ceramic powder having an average particle size of 15 µm. Superplastic forming was effected by a hot pressing (HP) process. The HP conditions included a temperature of 1,100°C, a pressure of 20 MPa, and a time of 20 minutes. At the end of HP forming, the assembly, that is, artificial dental root was taken out of the SiC ceramic mold. The dental root of this example was equivalent to that of Example 2 with respect to bond strength, flexural strength and biological affinity. Example 4 Stock materials of CaO, SiO₂, and MgO were mixed to provide compositions corresponding to the diopside, akermanite, wollastonite, alite, or belite fields as shown in Table 1. With a binder added, the compositions were press molded and then sintered at 1,200 to 1,360°C for two hours. The sintered ceramic materials had a grain size in the range of from 0.7 to 1.5 µm and a relative density of 99.5% or higher. Table 1 also reports the content (in % by volume) of the ceramic composition in the sintered body as measured by an X-ray powder diffraction method. The sintered materials were subjected to HIP super-plastic forming at a forming temperature of 1,100 to 1,170°C as described in Example 2. The resulting articles showed satisfactory bond strength, flexural strength and biological affinity and were thus suitable as dental roots. Example 5 A cylindrical substrate of titanium having a diameter of 5 mm and a height of 10 mm was blasted with 100-mesh steel shots. Titanium particles of 150 to 250 mesh were applied to the blasted surface of the titanium substrate by plasma spraying at a voltage of 60 V and a current of 500 A in an atmosphere of argon/hydrogen (5:1). The substrate was further coated with a dispersion of diopside powder of 60 to 100 mesh in water and dried. The diopside coated substrate was covered with BN ceramic powder, enclosed in a silica glass envelope, and subjected to superplastic forming by an HIP process. The HIP forming conditions included a temperature of 1,000°C, a pressure of 20 MPa, and a time of 30 minutes. At the end of HIP forming, the glass envelope was broken and the BN powder was brushed off. There was obtained an artificial dental root having a diopside coat layer joined to the root substrate. The dental root of this example was equivalent to those of Examples 2 to 4 with respect to bond strength, flexural strength and biological affinity. Example 6 Artificial dental crowns were fabricated. Hollow cylindrical sintered covers were prepared as in Examples 2, 4, and 5. The covers were fitted over coronal substrates of titanium. The assembly was subjected to HIP superplastic forming under the same conditions as used for the dental roots. The resulting dental crowns showed excellent properties equivalent to those of the dental roots. There has been described a living hard tissue replacement or implant fabricated by the superplastic forming of a ceramic material containing CaO and SiO₂. The superplastic forming ensures ease of shaping to a complex profile, eliminating a need for profile finishing by machining. There is no chance that flaws which would induce cracks during repetitive use be introduced into the replacement. The outer surface of the replacement as formed has a desirable irregular complex profile which cannot be reproduced by machining. The ceramic material, typically diopside can be joined to a heterogeneous material by an HIP process. There is obtained a living hard tissue replacement having a diopside layer firmly bonded to a substrate of heterogeneous material. A joint can be established at relatively low temperatures. The method for superplastic joining a ceramic coating to a substrate often uses hot isostatic pressing (HIP) for taking its advantage of even application of pressure to the object and thus produces an integrated article which leaves no gaps at the substrate-coating interface, exhibits an increased bonding force, and experiences no or little interfacial delamination during repetitive use. Since no exfoliation occurs with an increasing thickness of a coat layer of sintered ceramic material or sintered composite material, the coat layer can have any desired thickness. The coat layer may be either as thin as about 1 µm or as thick as about 10 mm. The coat layer thickness may be selected over the wide range depending on the intended use. In addition, the coat layer can be applied to a uniform thickness without a substantial variation and to a complex configuration with ease. The variation in quality among products is minimized. The replacements can be controlled to any desired surface roughness through a choice of the particle size of ceramic powder to be filled around the ceramic material or coating/substrate assembly during HIP or HP forming. An integrated body can be prepared from a substrate and a cover by shaping only the substrate to a precise configuration, fitting the ceramic cover of a roughly conforming shape over the substrate, and subjecting the assembly to superplastic forming. Steps of shaping, bonding, and surface treatment can be concurrently performed by a single forming step, with the benefits of eliminated need for machining and increased efficiency of working and manufacture. A plurality of integrated bodies can be produced at the same time so that a cost reduction is expectable from potential mass production. It is also possible to apply an HIP or HP process to a substrate coated with a superplastic ceramic material in powder form. This embodiment achieves a further cost reduction by omitting a step of pre-forming a cover by sintering. The living hard tissue replacements of the invention have extremely high mechanical strength and toughness as compared with those composed solely of calcium phosphate base ceramic materials. In summary, the present invention enables economical production of living hard tissue replacements featuring improved mechanical strength, biological affinity, and formability and well suited as artificial dental roots and crowns.

Claims: A method for preparing a living hard tissue replacement comprising the step of superplastic forming a ceramic material which contains CaO and SiO₂ as essential components, is substantially free from calcium phosphate, but capable of forming a calcium phosphate base compound upon contact with a phosphorus-containing aqueous solution. The method of claim 1 wherein said ceramic material further contains MgO in addition of the essential components CaO and SiO₂. The method of claim 2 wherein said ceramic material contains 10 to 90% by weight of CaO, 10 to 80% by weight of SiO₂, and 0 to 35% by weight of MgO. The method of claim 3 wherein said ceramic material has a composition belonging to any one of the diopside, wollastonite, akermanite, monticellite, alite, and belite fields. The method of claim 4 wherein said ceramic material contains at least 40% by volume of a diopside or wollastonite composition. A method for preparing an integral body comprising the step of: joining a ceramic material which contains CaO and SiO₂ as essential components, is substantially free from calcium phosphate, but capable of forming a calcium phosphate base compound upon contact with a phosphorus-containing aqueous solution to a material of different type by superplastic forming. The method of claim 6 wherein the step of superplastic forming of said ceramic material and said different type material for joining includes hot isostatic pressing. The method of claim 7 which further includes shaping said material of different type into a substrate and joining a cover of said ceramic material to the substrate. The method of claim 8 wherein said shaping step includes shaping the substrate to substantially the same shape as the living hard tissue replacement, and said joining step includes applying a cover of the ceramic material to said substrate and effecting hot isostatic pressing on the covered substrate through ceramic powder. The method of claim 6 which further includes shaping said material of different type into a substrate having substantially the same shape as the living hard tissue replacement, covering said substrate with the ceramic material, and effecting hot pressing, thereby joining said ceramic material to the substrate. The method of claim 10 wherein said substrate covered with said ceramic material is hot pressed through ceramic powder. The method of any one of claims 6 to 11 wherein said ceramic material further contains MgO in addition of the essential components CaO and SiO₂. The method of claim 12 wherein said ceramic material contains 10 to 90% by weight of CaO, 10 to 80% by weight of SiO₂, and 0 to 35% by weight of MgO. The method of claim 13 wherein said ceramic material has a composition belonging to any one of the diopside, wollastonite, akermanite, monticellite, alite, and belite fields. The method of claim 14 wherein said ceramic material contains at least 40% by volume of a diopside or wollastonite composition.

Inventors: NONAMI TOHRU, YASUI NOBUO, NONAMI, TOHRU, YASUI, NOBUO, NONAMI, TOHRU, C/O TDK CORPORATION, YASUI, NOBUO, C/O TDK CORPORATION
Applicants: TDK CORP, TDK CORPORATION
Application year: 1990
Main classification: A61L27
IPC codes: A61L27, C04B37, C04B35, A61F2, A61C8, A61K6