WO2015147741A1

WO2015147741A1 - Monolithic bodies of chemically bonded ceramic (cbc) biomaterial for implantation, preparation and use thereof

Info

Publication number: WO2015147741A1
Application number: PCT/SE2015/050378
Authority: WO
Inventors: Leif Hermansson; Jesper LÖÖF; Emil Abrahamsson
Original assignee: Doxa Aktiebolag (Publ)
Priority date: 2014-03-28
Filing date: 2015-03-30
Publication date: 2015-10-01

Abstract

The present invention generally relates to the use of pre-formed bodies of Chemically Bonded Ceramics (CBCs) biomaterial for implantation purposes wherein the bodies are prepared ex vivo allowing process parameters to be optimized for desired long term properties of the resulting CBC biomaterial. The pre-formed body of CBC material is machined to the desired geometry and the hardened CBC material implant is then implanted using a CBC cementation paste. The invention also relates to a method of preparing pre-formed hardened bodies of CBC biomaterial for implantation purposes, methods of preparing an implant thereof having desired geometry, and a method of implantation of the implant, as well as a kit for use in the method of implantation.

Description

MONOLITHIC BODIES OF CHEMICALLY BONDED CERAMIC (CBC) BIO- MATERIAL FOR IMPLANTATION, PREPARATION AND USE THEREOF

TECHNICAL FIELD

The present invention generally relates to the use of pre-formed bodies of Chemically Bonded Ceramics (CBCs) biomaterial for implantation purposes wherein the bodies are prepared ex vivo allowing process parameters to be optimized for desired long term properties of the resulting CBC biomaterial. The pre-formed body of CBC material is machined to the desired geometry and then implanted using a CBC cementation paste. The invention also relates to a method of preparing pre-formed bodies of CBC biomaterial for implantation purposes, methods of preparing an implant thereof having desired geometry, and a method of implantation of the implant, as well as a kit for use in the method of implantation.

STATE OF THE ART

In the art chemically bonded ceramics as biomaterials are known and have been described in a number of patent applications. A CBC material typically compris- es a ceramic cement binder system and inert particles. An organic binder system may be additionally be included as a complementary binder system to the ceramic cement binder system to provide e.g. cross-linking, which occurs at an earlier stage than the hydration of the ceramic cement binder system. Such materials are especially used in dental and orthopaedic applications. A number of requirements should preferably be fulfilled by such materials. The materials should i.a. be biocompatible. Properties required of the paste from which the biomaterial is formed, especially for dental applications, include good handling ability and a simple applicability in a cavity, moulding ability that permits good shaping ability, a hardening/ solidification of the material that is sufficiently rapid for filling work without detrimental heat generation. After hardening, the resulting biomaterial formed should also provide serviceability directly following therapy, a high hardness and strength, corrosion resistance, adequate bonding between the hardened biomaterial and surrounding biological tissue, radio-opacity, good long-term properties and good aesthetics of the resulting hardened material. With known CBC biomaterial systems the above desired properties cannot be optimized simultaneously. Optimisation of desired long-term properties generally negatively influences the workability and ease of application of the biomaterial, and a balance has to be struck between the desired properties.

For example, while it is known that improved mechanical strength and translucen- cy can be obtained with a higher degree of compaction, a higher degree of compaction is known to negatively influence the workability. E.g. WO 01 /76535 addresses this problem. The solution offered is to compact the powder composition into a raw compact using a reduced pressure. The resulting raw compact is then immersed into hydration liquid, and the wet raw compact is transferred to and inserted into e.g. a cavity in a tooth. An alternative solution is offered by WO 2004/000241. The solution offered is to use a higher degree of compaction and then to granulate the powder into highly compacted granules. An acceptable workability can thus be achieved. A paste can be formed from the granules and hydration liquid, which paste can thereafter be filled in a cavity.

A total system taking into account biological tissues, implant and cementation fixation of the implant of the same basic chemical system in the clinical situation while at the same time allowing for optimizing the desired long-term properties of the resulting biomaterial is still missing.

SUMMARY OF THE INVENTION The present invention is based on the use of a pre-formed body of CBC biomaterial, which is formed into desired geometry, hydrated, and hardened ex vivo, i.e. outside the human or animal body. Thereby optimum long-term properties, notably mechanical strength and translucency can be achieved in the CBC biomaterial. An implant closely matching the geometry of the cavity to be filled is formed from the preformed CBC biomaterial body, e.g. using CAD/CAM, or similar methods. Machining the preformed CBC biomaterial body to the desired geometry is preferably performed on-site (e.g. chairside) where the implantation is to be carried out. The machined implant is then fixed or "glued" to the cavity using a CBC cementation paste.

The inventive implant and the cementation paste can be based on chemical compo- sitions so as to provide a complete biomaterial system with chemistry close to that of surrounding hard tissue (enamel, dentine and cortical bone) .

In a preferred embodiment the inventive ceramic cement binder system of the CBC material and cementation paste is summarized as CaO-Al O3-SiO -P₂Os-H 0 (CASPH).

Preparing the pre-formed body of hardened CBC biomaterial ex vivo allows for a substantial higher degree of freedom of the system and its constituents, e.g. the typically very high pH of the hydrating system does not have to be modified so as to be tolerable in vivo, and the reactivity of the hydrating system does not have to be kept reasonably low in order not to evolve too much heat so as to be tolerable in vivo, and/or in order not to harden too quickly. The pre-formed hardened body of CBC biomaterial can thus be made using optimum pH, temperature, compaction pressure, hydration times, humidity and other conditions for achieving desired properties of the hardened material. By virtue of the present invention, the workability of a paste does not have to be considered when forming the implant material. According to the present invention, any workability limitations will solely apply to the cementation paste. The invention primarily relates to dental applications, where geometry, and a similar chemistry will contribute to avoidance of tension, both mechanically and thermally, as well as to avoidance of post-operative problems.

In one aspect the present invention relates to the use of a pre-formed hardened raw monolithic CBC material body for implantation purposes.

In another aspect the present invention relates to a method of preparation of a raw monolithic hardened body of CBC biomaterial, from which the inventive implant may be formed, comprising the following steps: A providing a CA-, CS or CAS- system CBC powder; B compacting the CBC powder in a confined volume using pressing means into a green body using a pressure of at least 25 MPa; C providing an aqueous hydration liquid; and, D hydrating the green body using the aqueous hydration liquid at a temperature of above normal human body temperature, preferably at a temperature in the interval of 50-90°C, so as to obtain a hardened body of CBC biomaterial.

Machining the preformed CBC biomaterial body to the desired geometry can be made on the green body of dry powder as obtained after pressing of the powder, which machined body is thereafter hydrated to a hardened CBC biomaterial im- plant, or on the pre-formed CBC biomaterial body which is in the process of being hydrated, i.e. on a partly hydrated pre-formed CBC biomaterial body, or on the fully hydrated, and thus hardened, pre-formed CBC biomaterial body.

Accordingly, in yet an aspect the present invention relates to a method of preparing a hardened monolithic CBC biomaterial implant comprising the steps of: AA-D providing a pre-formed hardened raw monolith CBC material body for implantation purposes, obtainable by means of the inventive method; E determining a desired geometry of the desired implant; and, F_c machining the body of hardened monolith CBC to the desired geometry, e.g. using CAD/CAM techniques.

In yet another aspect the present invention relates to a method of preparing a monolithic CBC biomaterial implant ex vivo wherein the machining step is carried out on merely a compacted body, or on a partly hydrated and hardened body, which method comprises the following steps: A providing a CA-, CS or CAS-system CBC powder; B compacting the powder in a confined volume using pressing means into a green body using a pressure of at least 25 MPa; C providing an aqueous hydration liquid; D hydrating the green body obtained in step B, optionally after machining thereof in step F, using the aqueous hydration liquid at a temperature of above normal human body temperature, preferably at a temperature in the interval of 50- 90°C, so as to obtain a hardened body of CBC biomaterial; E determining a desired geometry of the desired implant; and, F machining to the desired geometry, e.g. using CAD / CAM techniques, either: a) the compacted dry powder green body obtained in step B which machined body is thereafter hydrated in step D; or b) the partly hydrated body in step D which machined partly hydrated body is thereafter fully hydrated in step D. In yet an aspect the present invention relates to a hardened monolithic CBC material implant obtainable by means of the above methods. In another aspect the present invention relates to a method of implanting a monolithic hardened CBC biomaterial implant comprising the steps of: AA F providing a machined monolithic hardened CBC biomaterial implant, obtainable by means of either of the methods set out above; G providing a CA-, CS or CAS-system CBC powder; H providing an aqueous hydration liquid; I mixing the CBC powder and aqueous hydration liquid so as to obtain a cementation paste; J applying the paste obtained in step I to the machined monolithic body; K inserting the machined monolithic body with the paste applied thereupon obtained in step J into the site of implantation; and, L allowing the paste to harden at the site of implantation in vivo for fixation of the implant.

In yet another aspect the present invention relates to a kit for use in the implantation method comprising a preformed hardened raw monolithic CBC material body for implantation purposes; and a specified quantity of CBC powder, and a corresponding quantity of hydration liquid for forming a cementation paste thereof.

In preferred embodiments of the inventive implantation method and kit, the CBC powder and aqueous hydration liquid will be selected so as to form a cementation paste belonging to the CASPH-system. The inventive methods also allows for obtaining a C3AH6 single phase hardened

CBC material, which single phase material is associated with a markedly improved translucency.

Further aspects, advantages and embodiments will be apparent from the following detailed description and appended claims.

DEFINITIONS

"CA-system" is used herein to denote a ceramic cement binder system based on any phases of calcium aluminate (CaO-AbOa). "CS-system" is used herein to denote a ceramic cement binder system based on any phases of calcium silicate (CaO-Si02). "CAS-system" is used herein to denote a ceramic cement binder system containing phases of both calcium aluminate (CaO-AbOa) and calcium silicate (CaO-Si02), which system may be based on either calcium aluminate or calcium silicate.

"CASP-system" is used herein to denote a ceramic cement binder system containing phases of calcium aluminate (CaO-AbOa) and calcium silicate (CaO-Si02), which system may be based on either calcium aluminate or calcium silicate, additionally containing phases of calcium phosphate (CaO^Os) , which system may be summarized as CaO-Al₂0₃-Si0₂-P₂0₅. "CASPH-system" is used herein to denote a CASP-system additionally containing water, which system may be summarized as CaO-Al2O3-SiO₂-P₂Os-H₂0.

"CAH-system" is used herein to denote a CA-system additionally containing water, e.g. a fully hydrated CA-system.

"CBC powder" is used herein to denote the complete powder composition forming the CBC upon hydration thereof, which powder comprises the ceramic cement binder system, optionally inert particles, and optionally any additives. DETAILED DESCRIPTION OF THE INVENTION

The present invention is based on a unique utilization of a nanostructural chemically bonded ceramic system comprising both a pre-hydrated material (the implant) e.g. as an inlay or onlay prepared to the final geometry by CAD/ CAM or similar on- site (e.g. chairside) methods, and a cementation system for fixation of the preformed implant. The implant and the cementation paste may be based on similar chemistry to provide a complete biomaterial system with chemistry close to that of hard tissue (enamel, dentine and cortical bone). Such system is summarized as CaO-A^Oa- S1O2-P2O5-H2O (CASPH) . These findings in the first place relate to dental applications, where geometry, similar chemistry contribute to avoidance of tension mechanically and thermally, as well as avoidance of post-operative problems. The present invention will allow for an improved translucency to be obtained in the CBC material, by virtue of being formed ex vivo. Also, since higher pressure can be used, translucency can be obtained with less complex compositions, as compared to the compositions used for giving high translucency in materials from a paste.

The present invention also allows for the generally preferred calcium aluminate, not just the CaOxAl₂03 phase (CA), but the 3CaOxAl₂03 phase (C3A) to be used, which is otherwise typically considered too reactive to be used in vivo. Also, the reaction of heat associated with the use of C3A may often be limiting to its ap- plicability.

The inventive biomaterial system is based on chemically bonded ceramics, wherein the ceramic phase is based on Ca-aluminate and/or Ca-silicate. The present invention is based on findings related to a specific chemical system based on materials produced from the CaO-Al₂O₃-SiO₂-P₂O₅-H₂0 (CASPH). The CASPH is close in chemistry to that of body hard tissues such as enamel, dentine and different bone structures. The complete system comprises 4 aspects which all are essential. These aspects relate to 1) a premade implant, 2) configuration of the implant, 3) in situ preparation of the final geometry in the clinical situation, and 4) cementation of the implant.

The premade implant is prepared outside the body to yield a high strength implant. The formation of the premade implant takes into account the following aspects; a) temperature above body temperature, b) pressing of the original powder to a high density, c) hydration of the material using water based liquid, and d) to achieve an acid resistance material, as well as e) highly bioactive and translucent materials.

The invention generally relates to dental materials and implant materials used in hard tissue. The invention is aimed at producing biomaterials for dental applica- tions with special reference to dental filling materials including underfillings and sealants, and general bone void filling.

A second binder system - a cross-linking organic binder system which provides for initial crosslinking of the freshly mixed paste - can be included in the cementation paste.

The invention is described in more detail below with special reference to development of the selected chemical system, the pre-formed CBC biomaterial body and methods to prepare the final geometry of the implant.

The chemically bonded ceramic system of the pre-formed body.

The ceramic cement binder system of the chemically bonded ceramic system of the invention is based on calcium aluminate (e.g. CA, C3A) and /or calcium sili- cate (e.g. CS) phases, i.e. the ceramic cement binder system is a CA-, CS, or

CAS-system. In a preferred embodiment the ceramic cement binder system of the chemically bonded ceramic system of the invention is based on calcium aluminate (i.e. a CA-system), and the preferred phases are C3A and CA, especially C3A. The mean particle size of any particles present in the original powdered material should be below 10 μπι, and the amounts of the chemically bonded Ca-aluminate phases should correspond to a c/w ratio close to complete conversion, the latter favoring general low porosity in the microstructure, comprising mainly of

nanostructures including nano-porosity. Lower contents of phases from the

system and/ or system are also preferred, especially from the

system to facilitate formation of apatite phases.

Accordingly, in a preferred embodiment the ceramic cement binder system of the pre-formed implant is a CASPH-system, preferably based on calcium aluminate, the preferred phases of which are C3A and CA, especially C3A.

In a preferred embodiment the raw monolithic body of CBC biomaterial, from which the inventive implant is formed, is prepared using a CA-, CS or CAS-system CBC powder comprising the phase C3A. In especially preferred embodiments of the inventive monolithic CBC material the ceramic cement binder system consists of a CA-system, wherein only CA-phases are present, containing at least 90% by weight of the phase C3A. By using the phase C3A as the cement binder system, a single phase, i.e. C3AH6 can be obtained in the resulting hardened material. The use of C3A as the single phase in previous in vivo CBC hardening methods has not been possible, due to the reactivity of the C3A phase powder. A single phase C3AH6 CBC implant material has consequently not been suggested in the prior art. Presence of other CA phases in the cement binder system can be tolerated up to 10 % by weight of the cement binder system in order not to compromise the improved translucency of the resulting hardened material, but should preferably be kept to a minimum.

Compaction of the premade implant

The powder is compacted using any traditional pressing techniques, including general pressing and isostatic pressing. The pressing technique gives the compacted material a high density. The total porosity is favorably below 45 vol-%, preferably in the interval 30-40 % depending on the exact selected composition of the material. The pressure used is at least 25 MPa, e.g. within the interval of 50-350 MPa, pref- erably about 100 to about 300 MPa, typically from 100 MPa to 280 MPa.

Forms and sizes of the pre-formed raw body

Suitable dimensions of individual pre-formed raw bodies are e.g. in the interval of 3-8 mm. A suitable shape is e.g. rods, tablets, or platelets. The preformed bodies can be provided with notches, or portions with otherwise markedly reduced cross- sectional area, so that individual bodies easily can be broken off from a larger body.

Hydration temperature.

The premade implant is hydrated outside the body allowing hydration temperatures above body temperature. The preferred hydration temperature is in the interval 50- 90°C.

The hydration liquid

The bulk of the liquid used is water. For the pre-made implant pure water is pre- ferred. The nanostructure.

The inventive requirements of the microstructure of Ca-aluminate and/ or Ca- silicate based biomaterials allow the total biomaterial to be on the nanoscale level after hydration. This refers both to the premade biomaterial and the cementation paste by:

a) The general nanostructure developed in the CASP-system;

b) A nanoparticle/ crystal size of hydrates in the interval 15-40 nm;

c) A nanoporosity size of 1-4 nm;

d) Original particle size of the reacting chemically bonded ceramics of < 10 μαι.

The use of a premade implant using a compaction pressure of at least 25 MPa will guarantee that the nanostructure also will:

a) be free of large pores from handling aspects

b) exhibit a low content of nanopores, preferably below 10 vol-%, most preferably below 7 %.

The inert filler particles in the premade implant

A complementary inert filler material in the premade implant is preferably used to enable complete hydration of the ceramic cement binder system. A preferred inert filler is a glass with a refractive index close to that of the hydrated phases, i.e. a refractive index in the interval 1.58- 1.67. The content of the inert filler system is preferably in the range 20-50 w/o of the ceramic cement binder system to provide conditions for complete hydration thereof.

The cementation paste

The cementation cement or paste is preferably based on the system CaO-AbOa- S1O₂-P₂O5-H₂O (CASPH). The ceramic cement binder system of the cementation paste will thereby exhibit a chemistry close to both the chemistry of the premade implant, e.g. the CAH system, and the chemistry of hard tissue, which is mainly a Ca-phosphate system. For optimum rheological and handling aspects a glass iono- mer system may be added. The CBC powder used for preparing the cementation paste is preferably based upon mono-phase CA. A suitable amount of the glass ion omer when used is for example about 15 % by weight of the CBC powder. The clinical and the in-situ preparation

The premade implant is given its final geometry using in the clinical present CAD/ CAM equipment or similar equipment on-site (e.g. chairside) or at general dental laboratory CAD / CAM equipment or similar equipment. The final cementation (the paste) is prepared in minutes just before treatment and the bond between the final implant and the tissue is established in minutes after treatment.

Machining the preformed CBC biomaterial body to the desired geometry can be made on the green body of dry powder as obtained after pressing of the powder, which body after machining thereof is hydrated to a hardened CBC biomaterial implant, or on the pre-formed CBC biomaterial body which is in the process of being hydrated, i.e. on a partly hydrated pre-formed CBC biomaterial body, or on the fully hydrated, and thus hardened, pre-formed CBC biomaterial body. Machining the green body of dry powder, or the partly hydrated pre-formed body will allow for greater ease of machining.

The present invention is preferably used as inlays, tooth fillings including underfill- ings, and fissure sealings. Other application fields according to the present inven- tion are within orthopedics, and as a carrier for drug delivery.

EXAMPLES

Description of raw materials and preparation

1. The calcium aluminate (C3A = 3(CaO)(Al203)) used was synthesised and treated according to the description below.

2. Deionised water.

3. Inert glass of the composition Si02-BaO-B203-Al203 in wt% 50-30- 10- 10 average particle size 0.4 μπι, d(99) <= 3 μπι.

4. LiCl as an accelerator for the cement paste hydration was used as a pre-prepared standard solution, p. a. quality.

EXAMPLE 1 Preparation of the powder and pressed rods /tablets The calcium aluminate used for this material was synthesized using high purity AI2O3 and CaC03. The appropriate amounts of the raw materials are weighed in to a suitable container (1:3 molar ratio). The powders are intimately mixed by tumbling in excess isopropanol. Thereafter, the isopropanol is removed, such as by evapora- tion of the solvent using an evaporator combining vacuum and heat and finally heating in oven. The next step is filling high purity AI₂O3 crucibles with the powder mix and heat treating it at 1340°C for 4h. After heat treatment the material is crushed using a high energy crusher, in this case a roller crusher with alumina rollers. After crushing the calcium aluminate is milled using an air jet mill (Ho- sokawa Alpine) to the specified particle size distribution with a d(99)v of < 10μπι and an average particle size of 4 μηι.

The final powder formulation is obtained in the following way: All powder components are weighed in with high accuracy according to the composition in Table 1.

Table 1: Composition of the final powder formulation for the implant.

The components are weighed into a glass beaker, and the beaker is thereafter placed in a dry mixer and the components are mixed for 3 hours. The next step after mixing is sieving through a 125 μπι sieve in order to homogenise the powder and remove large agglomerates. After sieving, the powder is transferred to a suitable container, which is then sealed and stored dry. The powder is pressed into tablets (diameter 5 mm and length 5 mm.). EXAMPLE 2

Preparation of the liquid

The LiCl is first dried at 150°C for at least 2 hours in order to remove physically bound water. The LiCl is weighed into a PE bottle so that the final composition after addition of the water will be 20 mM of LiCl. To the liquid Ca3(P0₄)2 is added in an amount of 2 % by weight. The liquid is now ready for use as a hydration liquid for forming, together with the CBC powder, a cementation paste for gluing the pre- hydrated implant to tooth/ tissue.

Preparation of the cementation paste

The CBC powder used is based on the mono-phase CaO AI2O3 (CA) and comprises 15% by weight of a glass ionomer. The powder is mixed by hand with a sufficient amount of the above liquid to form a paste.

EXAMPLE 3

Description of tests and results obtained

The powder was pressed into rods using two methods, viz. uniaxial pressing, and cold isostatic pressing, respectively. The uniaxial pressing was performed at a pressure of 100 MPa, and 140 MPa, respectively. The cold isostatic pressing was performed at 280 MPa.

The rods were hydrated in deionised water in a closed chamber at 60 °C for 4 hours. The humidity in the chamber was close to 100 %.

The premade hydrated implant according to the test conditions above were evaluated chemically, mechanically and biologically according to the table below. Each test comprised 12 samples. The tests were conducted using standard ISO testing, which comprises the following sections: Cytotoxicity (ISO10993-5), Sensitization

(ISO10993- 10), Irritation /Intracutaneous reactivity (ISO10993-10), Systemic toxicity (ISO 10993- 11), Sub-acute, sub-chronic and chronic toxicity (ISO10993-1 1), Genotoxicity (ISO 10993-3), Implantation (ISO 10993-6), Carcinogenicity (ISO10993- 3) and Hemocompatibility (ISO 10993-4). Material at ComThermal Hydrated Biocompa- Bio- Trans- pressure pression expansion Phase tibility activity lucency strength X 106/oC %

100 MPa 250 +- 12 8.8 +- 0.2 C3AH6 OK OK 17+- 2

140 MPa 280 +- 10 9.1 +- 0.1 C3AH6 OK OK 24 +-3

280 MPa 330 +- 12 9.2 +-0.2 C3AH6 OK OK 33 +-3 (isostatic)

The corrosion resistance test - using a water jet impinging technique - was conducted according to EN 29917: 1994/ISO 9917: 1991, where removal of material is expressed as a height reduction using 0.1 M lactic acid as solution of pH 2.7. The duration time of the test is 24 h. The test starts after 24 h of hydration. The test probe accuracy was 0.01 mm. Values below 0.05 mm per 24 h solution impinging are judged as acid resistant. No reduction was found.

Claims

1. A method of preparing ex vivo a monolithic hardened raw body of CBC bio- material for implantation purposes comprising the following steps:

A providing a CA-, CS or CAS-system CBC powder;

B compacting the CBC powder in a confined volume using pressing means into a green body using a pressure of at least 25 MPa;

C providing an aqueous hydration liquid; and

D hydrating the green body using the aqueous hydration liquid so as to obtain a hardened body of CBC biomaterial, characterized in that the hydration and hardening in step D is carried out ex vivo at a temperature of above normal human body temperature, preferably at a temperature in the interval of 50-90°C.

2. The method of claim 1 , wherein the CBC powder is a CAS-system CBC powder additionally containing phases of calcium phosphate, i.e. a CASP-system.

3. The method of claim 1 or 2, wherein the CBC powder is a CA-system CBC powder.

4. The method of any one of the previous claims, wherein the CBC powder is a CA- or CAS-system CBC powder and the predominant Ca-aluminate phase is C3A.

5. A method of preparing a monolithic CBC biomaterial implant ex vivo comprising the following steps:

A providing a CA-, CS or CAS-system CBC powder;

B compacting the powder in a confined volume using pressing means into a green body using a pressure of at least 25 MPa;

C providing an aqueous hydration liquid;

D hydrating the green body obtained in step B using the aqueous hydration liquid, so as to obtain a hardened body of CBC biomaterial,

characterized in that the hydration and hardening in step D is carried out ex vivo at a temperature of above normal human body temperature, preferably at a temperature in the interval of 50-90°C, optionally after machining the green body in step F set forth below, ; and in further comprising the additional steps of

E determining a desired geometry of the desired implant;

F machining to the desired geometry, e.g. using CAD /CAM or other chairside techniques, either: a) the compacted dry powder green body obtained in step

B which machined body is thereafter hydrated in step D; or b) the partly hy- drated body in step D which machined partly hydrated body is thereafter fully hydrated in step D; or, c) the fully hydrated body obtained in step D.

6. The method of claim 5, wherein the CBC powder is a CAS-system CBC powder additionally containing phases of calcium phosphate, i.e. a CASP-system.

7. The method of claim 5 or 6, wherein the CBC powder is a CA- system CBC powder.

8. The method of any one of claims 5-7, wherein the CBC powder is a CA- or CAS-system CBC powder and the predominant Ca-aluminate phase is C3A.

9. A method of preparing a hardened monolithic CBC biomaterial implant com- prising the steps of:

A_{A D} providing a pre-formed hardened raw monolithic CBC material body for implantation purposes, obtainable by means of the method of any one of claims 1 -4;

E determining a desired geometry of the desired implant; and,

Fc machining the body of hardened monolithic CBC material to the desired geometry, e.g. using CAD/CAM or other chairside techniques.

10. A machined hardened monolithic CBC biomaterial implant, preferably a machined hardened monolithic CBC C3AH6 single phase biomaterial implant obtaina- ble by means of the method of any one of claims 5-9.

1 1. A method of implanting a hardened monolithic CBC biomaterial implant comprising the steps of:

A_{A F} providing a machined hardened monolithic CBC biomaterial implant, obtain- able by means of the method of any one of claims 5-9; G providing a CA-, CS or CAS-system CBC powder;

H providing an aqueous hydration liquid;

I mixing the CBC powder and aqueous hydration liquid so as to obtain a cementation paste;

J applying the paste obtained in step I to the machined monolithic body;

K inserting the machined monolithic body with the paste applied thereupon obtained in step J into the site of implantation; and

L allowing the paste to harden at the site of implantation in vivo for fixation of the implant.

12. A kit for use in the implantation method of claim 1 1 , comprising a preformed hardened raw monolithic CBC material body, preferably a preformed hardened raw monolithic CBC C3AH6 single phase material body for implantation purposes obtainable by means of the method of any one claims 1-4; and a specified quantity of CA-, CS or CAS-system CBC powder, and a corresponding quantity of aqueous hydration liquid for forming a cementation paste thereof.

13. The kit of claim 12, wherein the composition of the cementation paste formed from the CBC powder and aqueous hydration liquid corresponds to the composition of the preformed hardened raw monolithic CBC biomaterial body.

14. The kit of claim 12 or 13, wherein the CBC powder is a CAS- or CASP-system CBC powder, and wherein the aqueous hydration liquid optionally contains phosphate, which powder and liquid will form a CASPH-system paste upon mixing thereof.

15. The kit of any one of claims 12- 14 in the form of a capsule mixing system containing the CBC powder and the aqueous hydration liquid in separate capsules.

16. Use of a preformed hardened raw monolithic CBC biomaterial body for implantation purposes.