WO2010122354A1

WO2010122354A1 - Hydroxyapatite material and methods of production

Info

Publication number: WO2010122354A1
Application number: PCT/GB2010/050670
Authority: WO
Inventors: Edward Henry Lester
Original assignee: PROMETHEAN PARTICLES Ltd
Current assignee: PROMETHEAN PARTICLES Ltd
Priority date: 2009-04-23
Filing date: 2010-04-23
Publication date: 2010-10-28
Anticipated expiration: 2011-10-23
Also published as: GB0906999D0

Abstract

New sheet, roll and tube morphologies of ceramic hydroxyapatite particles and nanoparticles and methods of synthesising ceramic particles in a continuous hydrothermal reactor. New morphologies of hydroxyapatite have been formed incorporating other substances inside and/or on the surface thereof.

Description

HYDROXYAPATITE MATERIAL AND METHODS OF PRODUCTION

The current invention relates to ceramic materials and methods of producing the same.

Although the following description refers exclusively to hydroxyapatite, it will be appreciated by those skilled in the art that the methods of the current invention can be used to produce other ceramic and bioceramic materials, such as tricalcium phosphates, aluminas and/or the like.

The hydrothermal synthesis of hydroxyapatite nanoparticle rods is known and is disclosed in Chaudhry et al.; Chem. Commun., 2006, 2286-2288. This journal publication discloses the use of a continuous flow hydrothermal process to produce crystalline nanoparticle rods of hydroxyapatite. The process uses a counter current mixing reactor to mix a liquid precursor feed with superheated water feed to produce the hydroxyapatite particles and thus the process is termed 'hydrothermal'. The liquid precursor contains all the reagents that are chemically bonded together to form the hydroxyapatite product. The superheated water feed is different to the liquid precursor feed as the water does not act as a reagent which is chemically incorporated and bonded in the hydroxyapatite product. The superheated water provides an environment for crystallisation of the product and heat to initiate the reaction to form the hydroxyapatite.

Patent publication WO2005077505 describes the use of such a counter current mixing reactor. In particular this reactor is used for the production of metal and metal oxide nanoparticles by hydrothermal synthesis using superheated and/or supercritical water. The aforementioned synthesis of hydroxyapatite particles has the disadvantage that only one solid morphology of particle can be produced.

It is therefore an aim of the present invention to produce new morphologies of hydroxyapatite.

It is a further aim of the present invention to selectively produce different morphologies of hydroxyapatite using hydrothermal synthesis.

It is a yet further aim of the current invention to selectively produce different morphologies of hydroxyapatite using hydrothermal synthesis in a counter current mixing reactor.

It is a yet further aim of the current invention to produce new ceramic materials.

In a first aspect of the invention there is provided hydroxyapatite material in a substantially planar sheet morphology.

In a second aspect of the invention there is provided hydroxyapatite material in a substantially tubular morphology.

In a third aspect of the invention there is provided hydroxyapatite material in a substantially rolled morphology.

In one embodiment the hydroxyapatite material produced is substantially in the form of particles.

In one embodiment the particle morphologies produced by selectively adjusting the reaction parameters are substantially sheets, tubes, rolls and/or rods of hydroxyapatite. Typically the morphologies are crystalline in form.

In one embodiment the particles are substantially nanoparticles. Typically nanoparticles are defined as having at least one dimension less than 100 nm. Further typically nanoparticles are between 1-100 nm in least one dimension

Typically the particles of tube morphology are substantially cylindrical in shape and include at least one aperture formed therein. Further typically the tubular morphology is substantially linear in shape and includes at least one aperture located along, or parallel to, the longitudinal axis of the hydroxyapatite material particles.

It will be appreciated by those skilled in the art that the apertures referred to are formed by the shape of the hydroxyapatite material and are different to pores formed in the same. Porosity in this context refers to the pores created by the crystalline structure of the hydroxyapatite material.

Typically the particles of the roll morphology substantially comprise at least one section of a particle of hydroxyapatite material coiled, or rolled, around an axis. Preferably the at least one section of hydroxyapatite material is a sheet of hydroxyapatite material coiled, or rolled, around an axis to form a substantially cylindrical shape.

In one embodiment the roll morphology includes at least one aperture. Typically the roll morphology is substantially linear in shape and includes at least one aperture located along, or parallel to, the longitudinal axis of the hydroxyapatite material. In one embodiment the roll morphology is similar in shape to the tubular morphology, however in the roll morphology at least one portion of hydroxyapatite material overlaps with another portion of the same material. Typically the overlap occurs as the hydroxyapatite is coiled, or rolled around an axis. Further typically, the sheet forming the roll morphology is coiled, or rolled, 2-3 times around an axis.

Typically the rod particle morphology is a substantially liner rod of hydroxyapatite material with no apertures formed therein.

In one embodiment the rolled and/or tubular morphologies are used to hold and/or wrap other materials.

Typically the one or more further materials include materials such as metals, metal oxides and/or polymers

In a further aspect of the invention there is provided a method of forming ceramic material by hydrothermal synthesis, wherein the method includes the step of mixing at least two precursors in a reactor.

Preferably the ceramic material is ceramic phosphate material which is formed by hydrothermal synthesis, wherein the method includes the step of mixing at least two precursors in a reactor.

In an aspect of the invention there is provided a method of forming hydroxyapatite material by hydrothermal synthesis, wherein the method includes the step of mixing at least two precursors in a reactor.

In one embodiment the hydrothermal synthesis is substantially continuous. In one embodiment one or more of the precursors is a fluid. Preferably one or more of the fluid precursors are aqueous solutions.

In one embodiment the temperature of at least one of the fluid precursors is higher than the temperature of the other precursors when entering the reactor.

In one embodiment the reactor is a counter current mixing reactor. Preferably the counter current mixing reactor is of the type described in patent document WO2005077505, incorporated herein by reference.

Typically the counter current mixing reactor continuously mixes two or more fluids of differing densities and comprises a first inlet and an outlet whereby one or more further inlets are diametrically opposed to the first inlet and are disposed within the outlet.

Further typically the inlets and/or the outlet are arranged in a substantially vertical configuration and the fluid of higher density is cooler than the fluid of lower density. By arranging the inlets and outlets in this way the warmer, lower density fluid is introduced into a cooler, denser fluid creating counter current mixing.

In one embodiment the one or more further inlets comprise a shaped nozzle, for example, a conical funnel.

In one embodiment the reactor is a device capable of mixing two or more fluids of differing densities in which the least dense fluid is introduced into the device in a downwards orientation relative to a upwards flow of denser fluid. In one embodiment at least one fluid precursor contains phosphate ions and at least one other fluid precursor contains calcium ions. Typically the ions are in an aqueous solution.

In a preferred embodiment at least one of the fluid precursors is an aqueous solution of ammonium hydrogen phosphate and/or at least one other fluid precursor is an aqueous solution of calcium nitrate.

In one embodiment the fluid precursors are pumped into the reactor. Typically at least one of the fluid precursors is heated, or preheated, prior to entering the reactor. Preferably the aqueous ammonium hydrogen phosphate precursor is heated by a preheater prior to entering the reactor.

In one embodiment the fluid precursor is an aqueous solution and the solution is heated so that the solute is a component of steam and/or superheated steam and/or the like.

Typically at least one of the fluid precursors is heated and/or supplied to the reactor under pressure, said pressure being above ambient and/or atmospheric pressure (atmospheric pressure is typically defined as substantially 101 kPa). Preferably two or more fluid precursors are supplied to the reactor under pressure.

In one embodiment any one or any combination of the pressure, precursor concentration, temperature, flow rate of fluids and/or fluid precursors, pH, wherein all the aforementioned are reaction parameters, can be varied to modify the size, shape, porosity and/or morphology of the hydroxyapatite material.

In one embodiment one or more surfactants can be added to one or more fluid precursors and/or added as additional precursors to modify the size and/or shape and/or porosity and/or morphology of the hydroxyapatite material.

In an alternative embodiment at least the sheet morphology produced is a substantially amorphous substance containing phosphate. Typically in this alternative embodiment the sheet morphology substantially comprises a non-crystalline amorphous phosphate.

Preferably the pH of at least one or more of the precursors and/or the pH inside the reactor is varied to modify the morphology of the hydroxyapatite material.

In one embodiment control of the pH of the precursors, the pH inside the reactor and/or the pH of the process influences the morphology of the hydroxyapatite material particles produced.

Typically a pH of > 10 allows the tube and/or roll morphology to be formed. Further typically a pH<9 allows the sheet morphology to be formed. Preferably a pH of 7-8 allows the sheet morphology to be formed.

In one embodiment increasing the pH increases the number of rolls, or coils of the roll particle morphology. Typically increasing the pH and/or temperature increases the amount of annealing between the walls of the tube morphology particles. Further typically increasing the pH and/or temperature anneals the wall of the tube morphology particles, essentially closing any apertures formed therein and thus producing rod morphology particles.

In one embodiment the pH of the heated fluid precursor is controlled to allow selection of the morphology of the hydroxyapatite particles. In one embodiment the pH of the fluid precursors is controlled by adjusting the concentration of the solute in the aqueous solution introduced into the reactor.

In one embodiment the pH of the one or more fluids in the reactor is adjusted by varying the flow rate of the fluid precursor containing an ammonium ion into the reactor and/or adjusting the concentration of the ammonium ions in said fluid precursor containing the same.

In one embodiment varying the pressure reaction parameter does not affect the size, shape, porosity and/or morphology of the hydroxyapatite material. The person skilled in the art will recognise that it is advantageous to conduct processes at lower pressures as they are less costly than high pressure processes.

In one embodiment increasing the concentration of one or more fluid precursors in solution increases the aspect ratio of at least the rod particle morphology.

In one embodiment lower concentration increases the aspect ratio of the tubes, rolls and/or rods. It will be appreciated by those skilled in the art that aspect ratio refers to the ratio of the longest dimension to the shortest dimension of an object. For example, the ratio of the length to the width, with respect to the linear tube, roll and rod morphologies of the present invention.

In one embodiment increasing the temperature of at least one of the fluid precursors decreases the aspect ratio of the hydroxyapatite particles. Typically increasing the temperature decreases the aspect ratio of tube, roll and rod morphologies. Further typically operating the reactor at 200 ⁰C yields substantially all tubes and/or rolls and operating at 350 ⁰C gives shorter tubes/rolls in comparison.

It is understood that increasing concentration beyond typical values does not influence morphology to a great extent, however there is evidence that wall thickness and/or the thickness of the sheets can be increased with increasing concentration.

Typically crystalline hydroxyapatite is formed at reactor temperature of approximately 200 ⁰C.

Experiments show that even at relatively low temperatures the reaction kinetics are efficient. This has been demonstrated by recycling or passing the reactor effluent through the reactor again with no new ceramic particles being formed.

In one embodiment the pore size of at least the tube morphology particles is less than 50 nm. Typically this pore size means that the hydroxyapatite material substantially behaves like an open pore system. For example, gas molecules can permeate through these open pores and pass out the other side. At low temperatures and pressures (< 1 bar) gas adsorbs on the inside surface of the HA tube but capillary condensation will only occur at pressures close to 1 bar. Therefore, emptying the pores will require lower pressures, forming a phenomenon called hysteresis. Kelvins equation dictates that pores with a size less than 50nm (generally referred to as mesopores (2-50 nm)) can condense gases at pressures close to ambient giving relatively high adsorption potential and showing a Type 4 isotherm, with hysteresis during adsorption and desorption. Typically the pore size is in the mesoporous range. In an aspect of the invention there is provided a method of producing hydroxyapatite particles by hydrothermal synthesis using at least two precursors in a reactor wherein the method includes the steps of adjusting one or more of the reaction parameters to allow selective formation of one of a number of different possible morphologies of said hydroxyapatite particles.

Typically the morphologies produced by adjusting the reaction parameters are sheets, tubes, rolls and/or rods of hydroxyapatite.

Further typically the materials are formed by using at least two precursors and adjusting one or more of the reaction parameters allows one or more of the morphologies to be selectively formed

In an aspect of the invention there is provided a ceramic material.

In one aspect of the invention there is provided a ceramic material obtainable by hydrothermal synthesis.

Typically the ceramic material is formed by hydrothermal synthesis in a counter current flow reactor.

In one embodiment the sheet morphology has improved barrier properties and/or is a more readily 'absorbable' form of calcium for tooth and bone construction, repair and/or reconstruction.

Typically the sheets have a surface area of >20 m²/g

In an aspect of the invention there is provided a method of forming at least one layer of hydroxyapatite material over at least one substance wherein the method includes the steps of forming the hydroxyapatite by hydrothermal synthesis and mixing at least two precursors in a reactor.

Typically the at least one substance is introduced into the reactor with at least one of the precursors. Alternatively the substance is added once the hydroxyapatite material has been formed.

In one embodiment the layer of hydroxyapatite material is formed around the substance by passing the substance through the reactor a second time with the pre-formed hydroxyapatite and/or hydroxyapatite precursors. Alternatively the preformed hydroxyapatite and the substance are mixed in a conventional manner in a conventional vessel such as a test tube and/or the like.

In one embodiment the substance is substantially metallic. Metallic includes compounds and mixtures of compounds including metal, metal ions, metal oxides and/or the like.

In one embodiment the substance is substantially polymeric.

Typically tube or roll morphology hydroxyapatite particles can act as a mould to form rods of metal or other metal compounds such as phosphates, nitrides and sulfides.

In one embodiment a metal rod is formed by locating a metal precursor, such as a metal salt, inside an aperture of a hydroxyapatite tube and/or roll morphology particle. The hydroxyapatite acts as a skin or mould, whereby when the metal precursor is chemically or thermally treated to form a solid rod of metal inside the aperture of the particle. Typically the metal precursor is located inside the tube and/or roll by both the metal precursor and the hydroxyapatite being in the same medium, for example water. Further typically the hydroxyapatite particles containing metal precursors that can then be separated from the medium and the metal containing particles treated to form the metal rods or tubes.

In one embodiment the hydroxyapatite 'skin' can be removed by washing the same with acid and/or the like.

In one embodiment the hydroxyapatite rolls or tubes are filled with magnetic material such as magnetite and/or the like. Typically when such a material is used for bone repair and/or filling and/or the like, the repaired area clearly shows up on MRI scans and X-rays and the like.

In one embodiment the hydroxyapatite rolls or tubes are filled with silver. Typically when such a material is used for bone repair and/or filling and/or the like, the repaired area has antimicrobial properties or conductive properties for electronics.

In one embodiment hydroxyapatite rolls or tubes are filled with fluorescent materials or materials with fluorescent properties. Typically such fluorescent materials include any or any combination of fluorescent ceramics, metals, mixed metals (for example CdSe) or metal oxides, or metal sulfides (for example ZnS)

In one embodiment hydroxyapatite rolls or tubes are filled with europium oxide nanoparticles. Typically when such a material is used for bone repair and/or filling and/or the like, the repaired area has fluorescent properties. In one embodiment composite materials are produced by forming a first rod of a first metal inside the hydroxyapatite 'skin' or mould and then introducing a second metal. Typically the second metal is thermally and/or chemically treated to form a composite rod of both metals inside the hydroxyapatite 'skin' or mould. Further typically the hydroxyapatite skin can be removed by an acid wash to yield a composite metal rod.

Typically such composite metallic materials have applications in electronics where control of the morphologies, structures and shapes are critical to influence conductivities.

It is appreciated by those skilled in the art that the metallic precursors could be replaced with monomers to form polymer composites and/or metal-polymer composites.

In one embodiment at least one polymer is added to at least one fluid precursor and/or to the hydroxyapatite material once the same is removed from the reactor. Typically the polymer is polyvinylpyrrolidone (PVP). The addition of polymer and/or monomers does not appear to influence the morphology of the particles formed.

Further typically the polymer containing the hydroxyapatite can be used for bone scaffolds and/or the like. This application has the advantage of avoiding the use of complicated foaming processes to give porosity to the hydroxyapatite. Porosity can also be achieved by firing or sintering the hydroxyapatite.

In one embodiment the addition of metal precursors causes metal nanoparticles to form on the inside of the tubes and/or rolls. Typically the metal precursors are metal salts. In one embodiment adding silver salts to preformed hydroxyapatite rolls and/or tubes causes silver nanoparticles to spontaneously form of the surface of the same. Typically the mixture is heated to approximately 100 ⁰C for this to occur.

In one embodiment in order to introduce metal nanoparticles into the inside of the tubes and/or rolls, preformed rolls and/or tubes and preformed nanoparticles are mixed together.

Specific embodiments of the invention will now be described with reference to the following figures, wherein:

Figure 1 is a schematic view of the hydrothermal apparatus in accordance with one aspect of the invention;

Figures 2 a and 2b show TEM (transmission electron microscopy) images of the different morphologies of hydroxyapatite particles in accordance with an aspect of the invention;

Figures 3a and 3b show graphic representations of the new morphologies of hydroxyapatite particles in accordance with aspects of the invention;

Figures 4a- c shows TEM images of the effect of temperature on the morphology of hydroxyapatite in accordance with an embodiment of the invention;

Figure 5a and 5b show images produced by scanning electron microscopy (SEM) of hydroxyapatite synthesised at different temperatures in accordance with one embodiment of the invention; Figure 6 shows a TEM image of tube morphology hydroxyapatite in accordance with one aspect of the invention;

Figures 7a and 7b are graphical representations of using hydroxyapatite roll morphology particles to cover other materials, such as polymeric and/or non solid materials, in accordance with one aspect of the invention;

Figures 8a- c are graphical representations of using hydroxyapatite roll morphology particles to cover other materials in accordance with one aspect of the invention;

Figures 9a and 9c show TEM images of hydroxyapatite rolls containing other materials in accordance with one embodiment of the invention;

Figure 10 shows a schematic detailing the production of composite metallic rods using hydroxyapatite tubes in accordance with one embodiment of the invention; and

Figure 11 shows a schematic for the in-situ and ex-situ methods of forming metal rods in accordance with one embodiment of the invention.

Referring to the figures, there is shown new morphologies of hydroxyapatite particles and nanoparticles, and methods of producing the same. The particle morphologies are sheets, tubes, rolls and rods. The sheets, tubes and rolls are particularly interesting as these morphologies of hydroxyapatite have never been synthesised previously. In addition there is shown methods of using the new morphologies to produce other new materials, such as metallic rods, and their use according to embodiments of the present invention. Turning firstly to figure 1 where there is shown a schematic diagram of the apparatus used to produce the various hydroxyapatite particle morphologies i.e. sheets, tubes, rolls and rods.

It can be seen that the first fluid precursor, aqueous ammonium hydrogen phosphate solution, is pumped using an HPLC (high performance liquid chromatography) pump 2 into a pre-heater 4 before entering the reactor 6. The second fluid precursor, aqueous calcium nitrate solution, is pumped into the reactor 6 using a further HPLC pump 8. The first fluid precursor enters the reactor through a nozzle 10 and the second fluid precursor enters the reactor at the bottom. Because the first fluid precursor is heated it is less dense than the relatively cooler second fluid precursor. The first and second fluid precursors mix in a counter current fashion substantially at and around the end of the nozzle 12. It is also around this point that the synthesis and/or reaction to form the hydroxyapatite material occurs. Typically, once the reaction has occurred the material, water and any remaining precursors flow out of the reactor at the outflow, or exit 14, in the reactor which is located substantially at the top of the same. The flow is then cooled using a cooling unit 16 and the pressure of the fluid reduced to around atmospheric pressure using a back pressure regulator 18. The back pressure regulator includes a collection means for collecting the products from the reaction.

Figure 2a shows the sheet morphology 20 of the hydroxyapatite material produced from the apparatus described above. Typically the sheet morphology 20 is formed when the pH of the fluids inside the reactor is approximately < 9. Figure 2b shows a tube morphology of hydroxyapatite material. Typically the tube 22 or roll morphologies are formed when the fluids inside, or introduced into, the reactor have a pH greater or substabtially equal to 10. There are several variables that can be easily altered with this process including; precursor type, precursor concentration, pH, flow rates, flow ratios, mixing temperature and the use of additional surfactants. Each variable impacts on product characteristics e.g. decreasing the concentration of the two precursors by a factor of 4 from typical concentrations, increases the aspect ratio of the tubes and/or rolls from approximately 6 to over 20. By increasing the temperature of the superheated ammonium solution from 200 deg C to 300 deg C, at standard precursor concentrations, the aspect ratio is reduced from 6 to approximately 2. The typically flow rates and concentrations of the solutions are 20cc/min of 0.015M (NHJ₂HPO₄ and lOcc/min 0.05M Ca(NO₃)₂. At pH 7 the sheets have a surface area of 22m² /g and an apparent pore volume of 0.28 cc/g whilst tubes (pH of 10) have a surface area of 36m²/g and total pore volume of 0.37 cc/g. By rough estimation a 2D hydroxyapatite sheet with dimensions of 600- 800 nm across would correspond to 2-3 layers around a 50nm pore. The internal pore size of the tube-shape reveals pores of 30-60nm. Since some of the pores are in the mesoporous range (2-50 nm) they should undergo capillary condensation during nitrogen adsorption to give a Type IV isotherm.

Figures 3a and 3b show graphic representations of what a sheet morphology 20 and a roll morphology 24 look like when scaled up. The sheet 20 is relatively flat and planar. The roll 24 looks similar to a sheet that has been rolled, or coiled, around an axis. It is thought that the tubes may be rolled-up sheets and wherein the walls may fuse. The roll is substantially cylindrical in shape and has an aperture 26 that runs along the longitudinal axis of the roll.

Figures 4a- c are TEM images that show the affect of temperature on the shape and morphology of the hydroxyapatite material. It can clearly be seen from these images that increasing the temperature of the reactor decreases the aspect ratio (the ratio of the length compared to the width), of the hydroxyapatite material particles. The morphology of the particles in this example is tubular 24. This effect is further illustrated by the SEM images shown in figures 5a and 5b where length of the tubes formed at 200 ⁰C (figure 5a) are significantly reduced in length by raising the reactor temperature to 350 ⁰C (figure 5b).

The tube morphology 28 is shown quite clearly in figure 6, whereby a tubular particle is shown in cross section. It can be seen that the tube has a linear and substantially cylindrical shape defined by with walls 29 and a central cavity 31 with a diameter of approximately 50-60 ran in diameter.

Figures 7a and 7b and figures 8a-c are graphical representations of one technique of using hydroxyapatite roll morphology particles 30 to cover other materials. Typically the other materials may be polymers 32 and/or metals and/or metal oxides 34. In this embodiment these embodiments the hydroxyapatite particles wrap themselves around the material to be coated or covered. Once coated it can be seen that the materials 32,34 are wrapped in hydroxyapatite and occupy the aperture space which is located along the longitudinal axis of the roll morphology particle. In alternative embodiments the roll is already formed before the other material is located in the aperture space (not shown).

Figures 9a and 9b show TEM images of nanoparticles occupying the aperture in a tube morphology particle of hydroxyapatite. Figure 9a shows a single particle of silver 36 located inside the tube 38 substantially towards an end thereof. Hydroxyapatite material is thermally stable in comparison to metal and metal oxide nanoparticles and therefore the tube can act as a mould to form metallic rods, if the temperature is increased sufficiently to melt the metal inside and the same is then allowed to cool. The TEM in figure 9a shows the result of such a procedure, wherein the silver nanoparticles inside the tube have melted and then solidified inside the tube.

Figure 9b shows an alternative embodiment wherein an EuO₂ rod was pre-made and then flowed through the reactor with the hydroxyapatite precursors. The EuO₂ rod was wrapped inside a hydroxyapatite tube as the tube was formed. In further alternative embodiments rods of silver have been pre-made and flowed through the reactor with hydroxyapatite precursors to produce silver rods wrapped in hydroxyapatite tubes or rolls.

Figure 10 shows a schematic of an advancement of this technique whereby a metal composite rod is formed using copper and silver. Firstly, a copper rod 42 is formed inside a hydroxyapatite tube 44 by the aforementioned thermal technique of heating and cooling. Subsequently, silver 46 is added to the mixture and a copper rod capped at either end with silver is formed inside a hydroxyapatite tube 44, by once again heating and cooling. The tube 44 can be removed by washing the material with acid. The resulting composite rod can have a number of uses in the electronics industry and the like.

The formation of the rods can be formed in-situ, where for example a metal salt is added to one of the fluid precursor feeds before the hydroxyapatite is formed. Alternatively, the rods can be formed ex-situ wherein the hydroxyapatite tubes and/or rolls are first formed and then the metal subsequently added. These routes are detailed in figure 11. In addition to metals, polymer can be added in a similar fashion either ex-situ or in-situ. For example polymer rods can be made or the whole hydroxyapatite particle can be encapsulated in polymer. By encapsulating the particles in polymer the same can be prepared for use as scaffolds for tissue and/or bone and/or tooth growth.

Claims

1. Hydroxyapatite material wherein the morphology of the hydroxyapatite is in a substantially planar or tubular or rolled morphology.

2. Hydroxyapatite material according to claim 1 wherein the material is substantially in the form of particles at least a portion of which is crystalline.

3. Hydroxyapatite material according to claim 2 wherein the particles are nanoparticles.

4. Hydroxyapatite material according to any of claims 1-3 wherein the tubular and/or rolled morphologies are used to hold and/or wrap one or more further materials.

5. Hydroxyapatite material according to claim 4 wherein the one or more further materials are metals, metal oxides and/or polymers.

6. A method of forming ceramic materials by hydrothermal synthesis in a continuous counter current mixing reactor.

7. A method according to claim 6 wherein the materials are rods of hydroxyapatite.

8. A method of forming hydroxyapatite materials of the type of any of claims 1-5.

9. A method according to claim 8 wherein the materials are formed by hydrothermal synthesis.

10. A method according to claim 9 wherein the materials are formed by using at least two precursors and adjusting one or more reaction parameters allows one or more of the morphologies of to be selectively formed.

11. A method according to claim 10 wherein the precursors are fluids and at least one fluid precursor contains phosphate ions and at least one other fluid precursor contains calcium ions.

12. A method according to claim 11 wherein at least one of the fluid precursors is an aqueous solution of ammonium hydrogen phosphate and/or at least one other fluid precursor is an aqueous solution of calcium nitrate.

13. A method according to any of claims 10-12 wherein one or more surfactants can be added to one or more fluid precursors and/or added as additional precursors.

14. A method according to any one of claims 6-11 wherein one or more polymers are added to at least one precursor and/or the formed material.

15. A method according to claim 14 wherein the polymer is polyvinylpyrrolidone (PVP).

16. A method of forming at least one layer of hydroxyapatite material over at least one substance wherein the method includes the steps of forming the hydroxyapatite by hydrothermal synthesis and mixing at least two precursors in a reactor.