WO2001044141A2

WO2001044141A2 - Porous ceramic body

Info

Publication number: WO2001044141A2
Application number: PCT/NL2000/000915
Authority: WO
Inventors: Clayton Ellis Wilson; Walfridus Johannes Augustinus Dhert; Joost Dick De Bruijn
Original assignee: Isotis N.V.
Priority date: 1999-12-16
Filing date: 2000-12-13
Publication date: 2001-06-21
Also published as: WO2001044141A3; AU3242201A

Abstract

The invention relates to a process for preparing a porous ceramic body, which process is based on a negative replica method. The method includes the step of filling a porous organic structure, obtained by rapid prototyping, with an aqueous of ceramic material. The invention further relates to a ceramic body obtainable by said method and to its use as a scaffold for tissue engineering.

Description

Title: Porous ceramic body

The invention relates to a method of preparing a porous ceramic body and to a body obtainable by said method. The invention further relates to the use of said body as a scaffold m tissue engineering. Regeneration of skeletal tissues has been recognized as a new means for reconstruction of skeletal defects arising from abnormal development, trauma, tumors and other conditions requiring surgical intervention. Autologous bone grafting is considered the gold standard of bone transplantation with superior biological outcomes. However, autologous bone stocks are limited and often insufficient, particularly when large skeletal defects are encountered. Allografts are used as alternative materials but are associated with immunologically mediated complications and risks of disease transmission. Additional disadvantages of autograft and allograft materials include their limited potential for molding or shaping to achieve an optimum fit with bone voids.

As surgical techniques and medical knowledge continue to advance, there is an increasing demand for synthetic bone replacement materials, resulting from the limited supply of autograft materials and the health risks associated with the use of allografts. Hydroxyapatite has been investigated for use m the osseous environment for over 20 years, and the biocompatibility of the ceramic and its osteoconductive behavior is well established. Since porous HA is more resorbable and more osteoconductive than dense HA, there is an increasing interest m the development of synthetic porous hydroxyapatite (HA) bone replacement materials for the filling of both load-bearing and non- load-bearing osseous defects. Such technology could have the potential for restoration of vasculaπzation and complete penetration of osseous tissue throughout the repair site.

Variation of the scaffold design as three-dimensional superstructures has been demonstrated as an approach to optimize the functionality of bone regeneration materials so that these materials may be custom designed for specific orthopedic applications m the form of void fillers, implants, or implant coatings. In attempt to develop a skeletal cell and tissue carrier, which could provide optimal spatial conditions for cell migration and maintenance by the arrangement of structural elements such as pores and fibers, the feasibility of using "live" material is under investigation. Such live material could take the form of an open-porous implant system together with living tissue. In other words, this is so-called hard tissue engineering.

The most traditional way of preparing a porous HA ceramic is to use a foaming agent like hydrogen peroxide (H₂0₂) . In detail, an HA slurry is made by mixing HA powder with water and a H₂0₂ solution. Then, samples of the slurry are put m oven, under elevated temperature. H₂0₂ decomposes and 0₂ is released from the bulk material, leaving a porous structure. Until today, th s technique is still widely used m both clinical applications and research areas. However, porous ceramics made by this H₂0₂ method has an intrinsic shortcoming: it possesses only "laminar porosity". In other words, the pores are interconnected mostly m a laminar way, so there is no truly three-dimensional interconnected structure . Slip-casting is another way of synthesizing porous ceramics. The manufacturing route comprises preparing an HA slurry (slip) by mixing HA powder under stirring with water, a deflocculant and binder agents. In this slurry, a kind of foam (sponge) is immersed and pressed. As a result, the slurry will be sucked into the foam. A layer of ceramic will be coated on all the struts of the sponge after removing the extra slurry by squeezing the samples. Then the samples will be dried m microwave oven and finally sintered m a furnace. This method is often referred to as a positive replica method. Slip-casted materials are highly porous; they have a reticulate structure. However, due to the inner flaws m the ceramic, which are left after the sponge is burnt off, the strength of the material can not be increased to meet the requirement of tissue engineering application.

Meanwhile, coral HA has gained a wide interest m biomateπal spheres. An example of such a material is Interporeo, which has a high porosity and excellent microporous surface structure. However, it is an expensive material and, more importantly, its mechanical strength is insufficient for tissue engineering applications.

In summary, there are several known methods of preparing porous ceramics. However, there are specific requirements for porous ceramic which are to be used for skeletal regeneration, hard tissue repairing, and even for hard tissue engineering purpose. For bony tissue ingrowth, it is accepted that the pore size should be m the range of 100 to 300 microns, and the pores should be fully interconnected. This specification gives rise to a desire for a more suitable porous ceramic (tissue carrier or 3-D scaffold) .

The present invention provides an improved method for preparing a porous ceramic body. The method leads to a ceramic body having defined and controllable pore or channel size, pore or channel geometry, pore or channel mterconnectivity, net shape and architecture. These and other structural or architectural features may be deliberately designed into the ceramic body using this method. Cavities with the shape of tunnels or channels may advantageously facilitate the flow of culture medium through the ceramic body when it is used as a scaffold m tissue engineering and cells seeded onto it are being cultured. Furthermore, with the addition of designed structural features, the mechanical properties, particularly the compressive strength, of the ceramic body may be superior to those of ceramic bodies prepared by the above discussed, known methods. A process for preparing a porous ceramic body according to the invention is based on a negative replica method. More m detail, the present method comprises the steps of :

1) preparing a porous structure by rapid prototyping using an organic material, which is substantially insoluble m water, and is thermally decomposable into gaseous residues;

2) filling the porous structure with an aqueous slurry of a ceramic material;

3) drying the slurry; and 4) removing the organic material by thermal decomposition. As has been mentioned, the present method has the advantage that a ceramic body is obtained which has a porous structure consisting of interconnected pores. Moreover, a particularly high porosity can be achieved while maintaining superior mechanical properties.

In addition, it has been found that a ceramic body obtainable by the present method possesses a specific surface microstructure on all surfaces, including within the pores or channels. In other words, the surface of the ceramic body, including the surface within the pores, has a certain advantageous rugosity. By virtue of this feature, a good attachment of cells is obtained when cells are seeded onto the body, e . g . m tissue engineering applications. Also, by virtue of this feature the ceramic body may give rise to osteomduction. The above described ceramic materials prepared by a slip- casting method have been found not to have this feature.

Furthermore, the present method involves the use of rapid prototyping to prepare the negative structure for the negative replica method. This has the great advantage that a very accurate method is provided m which any architecture or geometry, regardless of its complexity, may be achieved. Moreover, because the design of the negative structure may be carried out using a computer, a very flexible operating method is provided. New designs can be optimized quickly at relatively low costs. This is particular advantageous m view of the intended application of the porous ceramic body as a scaffold for tissue engineering. Tissue engineering by its very nature, particularly when involving the use of patient specific cell cultures, requires but also provides a custom solution for each patient. The possibilities range from simply altering the overall size of an existing design for proper fit to offering a completely custom implant through integration of 3D medical imaging data { e . g. from CT or MRI scans) in the computer aided design process. As is mentioned above, first a porous structure of an organic material is prepared. It is necessary that the organic material is substantially insoluble in water, so that the integrity of the structure is not affected when it is filled with the (aqueous) slurry of ceramic material. Of course it is further necessary that the organic material is processable in a rapid prototyping protocol, which will be further discussed below. Another important requirement that has to be met by the organic material is that it should be removable by thermal decomposition. It is preferred that the organic material decomposes into volatile and/or gaseous residues upon exposure to temperatures above 200°C or 400°C. Depending on the envisaged application of the ultimate ceramic body, it is desirable that substantially no charred or tar- like residues are formed upon thermal decomposition, respectively remain within the porous structure of the ceramic body after sintering.

Suitable examples of materials that can be used to form the organic structure will readily be identified by the skilled person, based on the considerations presented above. Depending on the material chosen, an organic solvent may or may not be present. It will be clear that, if an organic solvent is to be used, it should be chosen such that it does not substantially interfere with the characteristics of the organic phase recited above. Without wishing to be exhaustive, the following suitable materials for use in the organic phase can be mentioned waxes, shellac, fatty acids, fats, epoxy resins, polyurethane resins, polyester resins, polyvmyl resins, poly (meth) acrylate resins, elastomers, thermoplastics and combinations thereof. Particular good results have been obtained using the proprietary thermoplastic (ProtoBuild ^m) used m the ModelMaker II 3D modeling system. Other suitable materials for use m the organic phase have been, and will be, developed by rapid prototyping system and material manufacturers and developers . The formulation of these materials is typically proprietary, however, the skilled person will be able to readily identify suitable materials by the material properties and characteristics described above.

The porous structure of the organic material is prepared using rapid prototyping The term rapid prototyping (RP) refers to a class of technologies that can automatically construct physical models from Computer-Aided Design (CAD) data. These 'three dimensional printers' allow designers to quickly create tangible prototypes of their designs, rather than just two dimensional pictures. At least six different rapid prototyping techniques are commercially available, each with unique strengths . Because RP technologies are being increasingly used m non-prototyping applications, the techniques are often collectively referred to as solid free- form fabrication, computer automated manufacturing, or layered manufacturing.

The latter term is particularly descriptive of the manufacturing process used by many of the commercial techniques. A software package 'slices' the CAD model into a number of thin layers, which are then built up one atop another. RP ' s nature allows it to create object with complicated internal features that can be manufactured by other means only with great difficulties, if at all.

Although several rapid prototyping techniques exist, essentially they all employ the same basic five step process. These steps are 1) create a CAD model of the design; 2) convert the CAD model to STL format; 3) slice the STL file into thin cross-sectional layers; 4) construct the model one layer atop another; and 5) clean and finish the model.

First, the object to be built is modeled using a Computer-Aided Design (CAD) software package. In accordance with the invention, use is preferably made of Rhinoceros^®

NURBS Modeling for Windows, which may be run on any suitable type of computer. It is possible to use a pre-existing CAD file or one can create a file expressly for prototyping purposes . The various CAD packages use a number of different algorithms to represent solid objects. To establish consistency, the STL (stereolithography, the first RP technique) format has been adopted as the standard of the rapid prototyping industry. The second step, therefore, is to convert the CAD file into STL format. This format represents a three dimensional surface as an assembly, or mesh, of planar triangles. The file contains the coordinates of the vertices and the direction of the outward normal of each triangle. For rapid prototyping it is important that the meshed surface is completely closed (watertight) . Most software packages that are available for producing STL files contain tools to accomplish this. Because STL files use planar elements, they cannot represent curve surfaces exactly. Increasing the number of triangles improves the approximation, but at the cost of a bigger size file. It will be clear that large, complicated files require more time to pre-process and build. The skilled person can suitably balance accuracy and manageability to produce a useful STL file. The CAD file is designed so that the rapid prototyping process will produce a negative replica of the desired ceramic body. Structural or architectural properties that may be defined during CAD file creation include, but are not limited to, pore or channel size, pore or channel geometry, pore or channel mterconnectivity, porosity, net shape and architecture, as well as variations of these parameters within a design. The requirements for these properties will depend upon the intended application. As an example, and as previously mentioned, for bony tissue ingrowth, it may be desired that pores should be fully interconnected and range m size from 100 to 300 microns. A skilled individual can determine the structural and architectural properties appropriate for a given application. In the third step of the RP process, a pre-processing program prepares the STL file to be built. Several programs are available and most allow the user to adjust the size, location and orientation of the model. Build orientation is important for several reasons. First, properties of rapid prototypes vary from one coordinate direction to another. For example, prototypes may be weaker and less accurate m the vertical directions than m the horizontal plane. In addition, part orientation partially determines the amount of time required to build the model . Placing the shortest dimension m the vertical direction reduces the number of layers, thereby shortening build time.

The pre-processing software slices the STL model into a number of layers of a thickness which can suitably be controlled, depending on the desired accuracy. Typically, the thickness of the layers will be between 0.01 and 0.7 mm. The program may generate an auxiliary structure to support the model during the build. Supports are useful for delicate features such as overhangs, internal cavities and thm-walled sections .

The fourth step of the RP process is the actual construction of the part. Using one of several techniques, RP machines build one layer at a time from polymers, paper, or other materials. Most machines are fairly autonomous, needing little human intervention. The techniques that can be use are primarily stereolithography, laminated object manufacturing, selective laser sintering, fused deposition modeling, solid ground curing, and mk et printing. These techniques are known per se, and m principle any of them may be used m the context of the invention. Preferably, however, use is made of mk et printing, e . g. as implemented m the ModelMaker systems which are commercially available from Sanders Prototype Inc., Wilton, New Hampshire, USA and is described m more detail m US patent 5,740,051, the contents of which are incorporated herein by reference. This machine uses two mkjets. One dispenses low-melt thermoplastic to make the model, while the other prints wax to form supports. After each layer, a cutting tool mills the top surface to uniform height. This yields extremely good accuracy. The process is repeated layer by layer until the entire 3-D model is constructed. The thermoplastic build material and wax support material that m accordance with the invention are preferably used by this system are proprietary formulations.

The final step of the rapid prototyping protocol is post -processing . This involves removing the prototype from the machine and detaching any supports. Some photosensitive materials need to be fully cured before use. Prototypes may also require minor cleaning and surface treatment. In accordance with the invention, this final step preferably comprises the removal of the support material as described by the manufacturer and a light rinse m water to remove loose debris .

In accordance with the invention, the porous organic structure is filled with a ceramic slurry. The ceramic material of which the slurry s prepared can m principle be any material of which it is desired to prepare a porous body of. In other words, the choice for a particular ceramic material will depend on the objective application of the final product . In view of the envisaged application of the porous body as a scaffold m tissue engineering, m accordance with the invention it is preferred that the ceramic material is a calcium phosphate. Highly preferred calcium phosphates may be chosen from the group of octacalcium phosphate, apatites, such as hydroxyapatite and carbonate apatite, whitlockites, α-tπcalcium phosphate, β- tπcalcium phosphate, sodium calcium phosphate, and combinations thereof.

Under certain circumstances it may be desired to incorporate an additive m the aqueous slurry. Examples of such additives are binders, surfactants, pH controlling agents, deflocculants, and the like. As binder, a water soluble polymer such as a cellulose derivative (e.g. carboxymethylcellulose (CMC) ) may be used, preferably m an amount of between 0.05 and 0.5 wt.%, based on the weight of the slurry. A pH controlling agent may suitably be employed to control the solubility of the ceramic material. It will be clear that it is to be avoided that (a significant amount of) the ceramic material dissolves m the aqueous phase. The skilled person will be able to determine whether there is a need for the use of a certain additive, based on his general knowledge .

The concentration of the ceramic material m the slurry will depend on the solubility of the chosen ceramic material m water. Generally, said concentration will be chosen between 50 and 80 wt.%, preferably between 55 and 75 wt.%, based on the weight of the slurry. The slurry may be prepared by admixing water and the ceramic material under stirring until a homogeneous slurry is obtained.

In case it is desired to prepare a ceramic body having a particularly high porosity, a foaming agent may conveniently be included m the ceramic slurry. The foaming agent may be present m the organic phase m amounts of up to 10 wt.%. A preferred example of a foaming agent is a combination of sodium bicarbonate and citric acid, which agents may suitably be employed m a weight ratio of between 1 : 2 and 1:5.

In another embodiment, combustible particulate matter, such as pine tree branches or rigid polymeric fibers, are incorporated m the slurry of ceramic material . This matter is meant to decompose when the organic phase is removed by thermal decomposition. As a result, a ceramic body is obtained which has additional discrete cavities m its structure which have the shape and size of the particulate matter that has been removed.

The filling of the porous organic structure with the ceramic slurry is preferably carried out by pulling the slurry through the porous structure by creating a vacuum using for instance a syringe. In order to facilitate this step, the porous organic structure may preferably be wrapped m a suitable material such as parafilm and mounted on Y₂ of an mime tubing filter. The syringe need only provide sufficient vacuum to enable the filling on the organic structure. It is also possible to push the slurry through the mold, again by using a syringe. It can be envisaged that virtually any vacuum or pressure source, including commercial vacuum and injection molding machines, may be used for this purpose .

When filled, the structure and tubing filter are preferably removed as a single piece. Subsequently, a drying step is carried out m order to dry the ceramic material. Preferably the drying is carried out for a duration of at least 5 hours at atmospheric conditions. If a more thorough drying is desired, the structure may be placed a low temperature oven at 50°C for this purpose.

The dried structure is subsequently placed m a furnace m order to thermally decompose, and remove, the organic material. Suitable conditions will depend on the nature of the organic material. Typically, thermal decomposition will be achieved at a temperature between 200 and 800°C. In order to ensure that the organic material substantially completely disappears, the heating may be prolonged for a duration of up to 24 or even 36 hours. After the thermal decomposition step, a porous ceramic body is obtained which may find application m itself. For many applications, however, it is preferred that the ceramic body is sintered. Sintering may be performed at a temperature between 800 and 1400°C, preferably between 1000 and 1300°C.

The thus obtained ceramic body has superior mechanical properties. In particular, it has a very high strength The compressive strength will preferably be at least 10 MPa Furthermore, the ceramic body has the structural and architectural properties as designed m the CAD file.

The above properties make the ceramic body highly suitable for use as a scaffold m tissue engineering. In this regard, the term tissue engineering is intended to refer to any process wherein cells are seeded onto the scaffold material and cultured there, either in vi tro or m vivo, to form tissue of a desired type. For the formation of tissue, cells of various types may be used ranging from stem cells to all sorts of differentiated cells. Due to its mechanical properties, the present porous ceramic body is particularly useful for tissue engineering bone tissue or for repair of defects at non-load bearing sites, but also at load bearing sites.

As mentioned above, the surface of a ceramic body according to the invention further has highly advantageous properties beneficial to cells with which it comes into contact. As the negative replica of the ceramic body is prepared using rapid prototyping, it is m fact built up of discernible layers. It has been found that at the interfaces of these layers, a certain roughness is produced. As the ceramic body is a replica of the body prepared m the rapid prototyping, it will possess the same, albeit the positive of the negative, type of roughness. This roughness has been found to be very beneficial to cells, m particular to the proliferation of cells. Accordingly, if the ceramic body is used as a scaffold for tissue engineering bone, the cells that are seeded onto the scaffold in vi tro or the cells that come into contact with or m the vicinity of the rough surface of the scaffold in vivo show a higher proliferation rate than the same cells would show when the surface would be smooth.

The roughness encompasses at least two elements. First, there are agglomerates or protuberances extending from the underlying surface ranging m size from 3 to 70 μm. Between and around these protuberances are gaps typically ranging size from 0.5 to 60 μm. Incorporated m the protuberances, and to a lesser degree m the entire surface m general, is a certain micro-porosity (holes and/or channels) presenting surface openings ranging m size from 0.1 to 10 μm. It will be understood that this roughness may be controlled by varying the thickness of the different layers that is applied m the rapid prototyping.

It has furthermore been found that the present ceramic body may be crushed to form a granulate of a desired porous structure. The granulate so obtained may find application for example oral surgery and plastic surgery of the face, as well as spine surgery and orthopedics. Preferably, the mean diameter of the particles of the granulate are between 2 and 3.5 mm.

The invention will now be elucidated by the following, non-restrictive example.

EXAMPLE A ceramic (hydroxyapatite) scaffold was desired for use m a critical size segmental defect of the goat femur. The design specifications were as follows. Overall shape and dimensions: Hollow cylinder Inner (hole) diameter: 10.0 mm

Outer diameter: 20.0 mm

Length: 25.0 mm

Internal porosity and features:

Completely interconnected network of orthogonal channels with a 600 μm square cross-sections. Porosity: 50%

Channel Cross-section: 600 μm square

The Rhinoceros NURBS Modeling for Windows software was used to design a negative replica mold (organic phase) according to the above specifications. A shrinkage of 20% for the ceramic material during drying and sintering, described later, was accounted for in the computer aided design process. The design specifications for the negative replica mold were as follows.

Overall shape and dimensions: Hollow cylinder

Inner (hole) diameter: 12.5 mm Outer diameter: 25.0 mm Length: 31.25 mm

Internal porosity and features: Completely interconnected network of orthogonal struts with a 750 μm square cross-sections. Porosity: 50% Strut Cross-section: 600 μm square

Essentially the struts were arrange in a "log pile" manner with each layer of struts (logs) perpendicular to the two adjacent layers. Within each layer the struts were spaced 750 μm apart, the same distance as the thickness of the struts, yielding the 50% overall porosity. Alternating layers were aligned.

Additional features, which had no effect on the final ceramic scaffold, were designed into the mold. The exterior circumference of the hollow cylindrical molds were enclosed and the central hole was filled. The two surfaces perpendicular to the cylinder axes were left open. This aided in the directional filling of the mold. To facilitate more efficient manufacture by a rapid prototyping processes, described m detail later, the mold was designed to be one fifth of the overall required length. This reduced the overall print time but required that five sub-molds be stack together to form a single complete mold. To allow the stack of five sub-molds to be aligned a rectangular through-and- through channel was designed along the axis of the cylindrical molds.

The Rhinoceros NURBS Modeling for Windows software was used for computer aided design of the sub-molds according to the above specif cations. This software package was also used to convert the CAD file to the STL file format required for rapid prototyping and to edit the STL mesh as needed to create a closed (watertight) model. A computer rendered image of one sub-mold section is showing m Figure 1. The STL file of a single sub-mold was sent via the internet to a rapid prototyping service bureau for per- processing and printing. The ModelWorks software (Sanders Prototype, Inc.) was used to pre-process the STL model for printing using the ModelMaker II 3D printing system (Sanders Prototype, Inc.). Using ModelWorks, five copies of the STL sub-mold model were arranged and oriented in the print envelope. The STL models were sliced in 53 μm thick slice/print layers. The slice/print layer thickness may be varied from as little as 13 μm to as much as 150 μm using the ModelWorks software and ModelMaker II printer. Thinner slice/print layers produce better resolution but require longer to print than thicker slice/print layer. A slice/print layer of 53 μm thick chosen as a compromise between resolution and print time. The software automatically determined the placement of thermoplastic build (ProtoBuild) and wax support (ProtoSupport ) materials. The sub-mold models were then printed. When printing was complete the printed models were removed from the machine. The wax support material was removed using and special solvent (BioAct). The remaining build material defined the negative replica sub- molds and they were designed. The cleaned sud-molds were sent via regular post to our facility.

Upon observation of the sub-molds received from the service bureau, surface perpendicular to the print plane revealed the print layers while surfaces parallel to the print plane did not. The dimensional accuracy of the sub- molds was very good, within 2% of the design dimensions. Loose debris was removed from the sub-molds by rinsing lightly in water. Figure 2 shows the top and bottom surface of one of the sub-molds as received from the service bureau.

The sub-molds were prepared for filling with hydroxyapatite slurry by first stacking and aligning the five sub molds to form a single complete mold. Alignment was facilitated by placing a tight fitting rectangular piece of cardboard into the rectangular alignment hole of the sub- molds. The five sub-molds were pressed together by hand and then circumferentially wrapped with several layers of parafilm. The ends of the assembled mold were left unobstructed. One end of the mold was placed against the filter side of one half of an ime tubing filter. An additional wrap of parafilm held the filter to the mold and formed and air tight seal. The other side of the tubing filter attached to a 60 ml disposable syringe. HA powder, purchased commercially and calcined at

1000°C, was used to prepare an aqueous slurry by admixing the ingredients listed m Table 1 m the specified amounts. Stirring was continued until a homogeneous slurry was obtained. The mold was filled with slurry by placing the open end of the mold to the slurry and pulling out the plunger of the syringe to create vacuum. The vacuum pulled slurry trough the mold. The vacuum was maintained until the mold was completely filled as verified by slurry entering the syringe. Table 1: Composition of HA slurry

The filled mold/filter assembly was removed from the syringe and allowed to air dry at room temperature for 24 hours. The filter and excess dried HA were removed from the filled mold. The filled mold was dried for an additional 4 hours an air atmosphere oven at 50°C. The thermoplastic mold material was burned out at 400°C and the ceramic final sintered at 1250°C according to the heating profile shown in Figure 3. The resulting ceramic scaffold is shown m Figure 4. Figure 4A shows the end of a hydroxyapatite cylinder which was produced by stacking five of the molds shown in figures 1 and 2. Figure 4B shows a side view of this cylinder. Scanning electron microscopy of scaffolds produce by this method show several interesting features. Impressions of the layer mold morphology were present m the sintered ceramic scaffold. Approximately 50% of the surface contained HA agglomerates ranging 5 to 20 μm size, particularly at the junction of print layers. The remainder of the surface was relatively smooth with some microporosity (<3 μm) . Grains were typically 2 to 4 μm and tightly packed. These surface microstructures have been shown to be advantageous for the attachment and proliferation of some cell types. Figures 5A and B show the advantageous surface microstructure of the cylinder shown m figures 4A and B.

The shrinkage of the resulting sintered scaffold was as expected, between 20 and 22%. FT-IR analyses showed that scaffolds produced by this method were pure HA.

Claims

1. Process for preparing a porous ceramic body comprising the steps of:

2) filling the porous structure with an aqueous slurry of a ceramic material;

3) drying the slurry; and

4) removing the organic material by thermal decomposition. 2. Process according to claim 1, wherein the organic material is chosen from the group of waxes, shellac, fatty acids, fats, epoxy resins, polyurethane resins, polyester resms, polyvmyl resms, poly (meth) acrylate resms, elastomers, thermoplastics, and combinations thereof. 3. Process according to any of the preceding claims, wherein the rapid prototyping involves mkjet printing.

4. Process according to any of the preceding claims, wherein the ceramic material is a calcium phosphate.

5. Process according to claim 4, wherein the calcium phosphate is chosen from the group of octacalcium phosphate, apatites, such as hydroxyapatite and carbonate apatite, whitlockites, α-tπcalcium phosphate, β-tπcalcium phosphate, sodium calcium phosphate, and combinations thereof.

6. Process according to any of the preceding claims, wherein the slurry comprises between 50 and 80 wt.% of ceramic material, based on the weight of the slurry.

7. Process according to any of the preceding claims, wherein the slurry is dried for at least 5 hours under atmospheric conditions.

8. Process according to any of the preceding claims, wherein the organic material is removed at a temperature of between 200 and 800°C.

9. Porous ceramic body obtainable by a process according to any of the preceding claims .

10. Porous ceramic body according to claim 9, having designed structural and architectural properties such as pore or channel size, porosity, mterconnectivity of pores or channels and a compressive strength of at least 10 MPa .

11. Use of a porous ceramic body according to claims 9 or 10 as a scaffold m tissue engineering.

12. Process according to any of the claims 1-8, wherein the porous ceramic body is sintered at a temperature of between 800 and 1400°C.

13. Porous ceramic body obtainable by a process according to claim 12.

14. Porous ceramic body according to claim 13 having designed structural and architectural properties such as pore or channel size, porosity, mterconnectivity of pores or channels and a compressive strength of at least 10 MPa.

15. Porous ceramic body according to claim 13 or 14 having a specific rough surface beneficial to cell proliferation.

16. Use of a porous ceramic body according to claims 13- 15 as a scaffold tissue engineering.

17. Process for preparing a porous ceramic granulate comprising crushing a porous ceramic body according to claims 9, 10, 11, 13, 14 or 15.

18. Porous ceramic granulate obtainable by a process according to claim 17 having a mean particle diameter of between 2 and 3.5 mm.