GB2354518A - Porous ceramic bodies; bone cell growth and drug carriers - Google Patents

Abstract

A porous ceramic body is made of bonded particles and has a defined pore size and true porosity. The pores may be infilled with bone cells or drugs. It is made by a process in which the body is fired at 125{C or 135{C for two hours.

Description

2354518 Agents ref.. P0301 I GB A POROUS CERAMIC BODY COMPOSED OF BONDED

PARTICLES The invention relates to a porous ceramic body composed of bonded particles and having predetermined physical properties.

GB-A-2142929 discloses a porous ceramic body for use, e.g. in bone regeneration and having pores in the size range of I to 600 micrometre, wherein some pores are connected to the exterior of the body via capillary voids.

US-A-5011495 discloses a 'disc' body for use in the promotion of bone growth comprising layers of porous tricalcium phosphate having randomly occurring nonconnected pores the majority of which are in the size range of 70 tO 420 micron.

It is one object of the invention to provide a method of making a porous article having controlled levels of porosity, interconnectivity, pore size, and mechanical properties suitable for use in various applications.

In one aspect the invention provides a porous ceramic body composed of bonded particles, having interconnected pores in the size range of at least 15 micrometre and a true porosity in the range of from about 20% to about 95% and which has been fired at 1250'C for two hours.

2 In another aspect the invention provides a porous ceramic body composed of bonded particles, having interconnected pores in the size range of at least 15 micrometre and a true porosity of from about 20% to about 95% and which has been fired at 1350'C for two hours.

In one preferred embodiment the pores are in the size range of 15 to 50 micrometre for use in encouraging fibrovascular ingrowth.

In another preferred embodiment the pores are in the size range of 50 to 150 micrometre for osteoid formation.

In another preferred embodiment the pores are in the size range greater than 150 micrometre to facilitate ingrowth of mineralised bone.

In yet another preferred embodiment the pores are infilled with bone cells or a drug.

The particles will be chosen according to the intended end use. As will be explained later, for the preferred use hydroxyapatite is present either alone or with other particles. The other particles can include both oxides and non-oxides such as alumina, mullite, silicon carbide, silicon nitride, zirconia, titanium oxide and the like. Preferably the particles have an average particle size less than about 5 micrometres and Preferably 95% of the particles will be less than about 2 micrometres. However, the particles can be much larger, say 100 micrometres or more.

3 It is a feature of the invention that the final articles formed consist essentially of the starting ceramic materials only, so avoiding the need for the removal of residual secondary e.g. inorganic binders. The article can thus consist of ingredients acceptable for medical use, e.g. as bone grafts for orthopaedic, surgical, dental and like uses both for humans and animals. There will always be a need to replace bone lost as a consequence of traumatic or non-traumatic events. Bone substitute materials are available and approved for clinical use. These materials have been successfully used in orthopaedics, dentistry and facial plastic surgery. Among the types of bone graft materials used, particular interest has been shown in the porous types which can provide a scaffold for in growth of connective tissue and bone. Studies have shown that pore sizes less than 10 micrometre prevent ingrowth of cells, pore sizes of 15 to 50 micrometre encourages fibrovascular ingrowth; pore sizes of 50-150 micrometre result in osteoid formation; and pore sizes greater than 150 micrometre facilitate the ingrowth of mineralized bone. Different approaches have been taken to try and mimic the hydroxyapatite frame work within both the cortical and cancellous bone. One material is based on the conversion of a coralline structure to hydroxyapatite material. With this process the selection of the coral with the correct pore structure is imperative before conversion takes place. Two corals were eventually selected exhibiting two different pore structures. These two pore structures are intended to replicate the different structures in cortical and cancellous bone. It is a feature of this invention that synthetic articles made by the method may be used as bone graft materials of high acceptability.

Hydroxyapatite [Ca10(P04), (OH)21 is an ideal candidate starting material. This material belongs to a group of calcium phosphates which are being considered as bone 4 substitute materials. The invention is applicable to hydroxyapatite and any other calcium phosphate (where the Ca/P atomic ratio may vary widely). In addition to this group of materials it may be advantageous to create an interconnected structure in another ceramic material such as alumina or zirconia for mechanical property reasons and either use the material as produced, or coated with a more bioactive material such as hydroxyapatite. It is another feature of this invention that the materials known as "Bioglass" could be converted in highly porous structures using this method.

The true porosity will range from about 20% to about 95%. The article formed is relatively robust after polymerisation and strong enough to be machined after removal of the liquid carrier.

The firing temperature and duration are selected according to the nature of the particles, e.g. alumina generally requires a higher sintering temperature than hydroxyapatite.

It is a feature of this invention to provide an article having a highly microporous structure if the sintering procedure is controlled. This microporous, structure can have advantages in certain applications e.g. it may be infilled with certain drugs such as antibiotics or growth factors, to act as a slow release agent at the site of an implant and it appears to encourage the easy attachment of in-growing bone cells compared to a dense microstructure.

The formed article may be in a variety of shapes, e.g. in the form of granules, bars, cylinders or rods, blocks or the like.

In order that the invention may be well understood it will now be described by way of illustration only by reference to the following examples and micrographs. The method is described and claimed in our copending Application No. of even date herewith.

Example I

Hydroxyapatite powder, ammonium acrylate monomer, methylenebisacrylamide, water, the ammonium salt of polyacrylate and the ammonium salt of polymethacrylate were mixed together to form a slurry which was subjected to a high shear mixer in order to remove any agglomerates within the slurry. This was transferred to a glove box within which the oxygen concentration was approx. 0. 1 %. A surfactant TERGITOL TMN 10 was introduced into the slurry and the whole was agitated in a mixer designed to introduce air so that a foam will be formed. The amount by which the ceramic solid is foamed is dependant on the final density required, the solids content of the slurry and the shrinkage which will occur at the later stages of drying and firing. The amount of surfactant added determines the extent of foaming, and this was selected to achieve the required final density. Once the foam density was achieved, ammonium persulphate (initiator) and tetramethylethylenediamine (catalyst) were injected into the foam to cause the acrylate monomer to start to polymerise. The time before the onset of polymerisation was about 1.5 minutes.

The mixture was restirred and allowed to stand. Polymerisation. began after about 1.5 minutes. A photo of the microstructure produced after an idle time of 1.5 minutes is shown in Figure 2. Once polymerised the foam was removed from the mould and 6 allowed to dry at room temperature for 2 days before being forced dried at 600 C in an oven.

At this point the "green" ceramic can easily be machined into the desired shape. The t4green" article was heated in a furnace to remove the organic binder and to cause the ceramic microstructure to densify. The sample was split in two and fired at two different temperatures. Sample I shown in Figure 3 and sample 2 in Figure 4 were fired at 12500 C for 2 hrs and 13500 C for 2 hrs respectively. It can be seen that the degree of microstructural densification can be adjusted with the sintering conditions. Sample I exhibits a highly connected microstructure whereas the microstructural porosity has been removed in sample 2. Live human bone cells were cultured. Both samples I and 2 were immersed in the cultures and Figures 5 and 6 show the results after 36 hrs immersion for sample 1 and 2 respectively. The bone cells can be clearly seen on the surface of the cell walls. From these Figures it appears easier for the bone to grow within the undersintered, microstructure than the fully densified, structure.

Example Il

The method of Example I was repeated except that the rate of addition of the initiator and the catalyst were selected so that the time before onset of polymerisation was 16 minutes instead of 1.5 minutes. A highly porous foarn exhibiting a larger cell size as shown in Figure 7 resulted. It can be seen from the different Figures that the time before the onset of polyrnerisation has had a major influence on the cell structure.

The Figures of the accompanying drawings are microphotographs as follows:

7 Figure I is a general foam; Figure 2 is a foam produced in Example I taken after an idle time of 1.5 minutes; Figure 3 is the polyrnerised foam of Example I fired at 12500C for 2 hours; Figure 4 is the polyrnerised foam of Example I fired at 13500C for 2 hours; Figure 5 is the fired product shown in Figure 3 after being immersed in a bone cell culture for 36 hours; Figure 6 is the fired product shown in Figure 4 after being immersed in a bone cell culture for 36 hours; and Figure 7 is the foam produced in Example II.

8

Claims (6)

1. A porous ceramic body composed of bonded particles, having interconnected pores in the size range of at least 15 micrometre and a true porosity in the range of from about 20% to about 95% and which has been fired at 1250'C for two hours.

2. A porous ceramic body composed of bonded particles, having interconnected pores in the size range of at least 15 micrometre and a true porosity of from about 20% to about 95% and which has been fired at 13500C for two hours.

3. A body according to Claim 1 or 2, wherein the pores are in the size range of 15 to 50 micrometre for use in encouraging fibrovascular ingrowth.

4. A body according to Claim 1 or 2, wherein the pores are in the size range of 50 to 150 micrometre for osteoid formation.

4. A body according to Claim I or 2, wherein the P[ores are in the size range greater than 150 micrometre to facilitate ingrowth of mineralised bone.

5. A body according to any preceding Claim, wherein the pores are infilled with bone cells.

6. A body according to any of Claims I to 6, wherein the pores are infilled with a drug.