WO2006091097A2

WO2006091097A2 - Two-dimensional and three-dimensional structures with a pattern identical to that of e.g. cancellous bone

Info

Publication number: WO2006091097A2
Application number: PCT/NL2006/050010
Authority: WO
Inventors: Shihong Li
Original assignee: Cam Implants B.V.
Priority date: 2005-01-14
Filing date: 2006-01-13
Publication date: 2006-08-31
Also published as: WO2006091097A3

Abstract

The present invention relates to two- and three-dimensional biocompatible, preferably porous, structures that are suitable for biomedical applications, especially as a component of prostheses. More particularly, the invention concerns a two- or three- dimensional structure that may be constituted from one or more metal sheets or foils, said structure carrying a pattern identical to that of a natural tissue such as cancellous bone. The invention also provides a method for producing a biocompatible as described above, which process comprises replicating an image of the natural tissue on a substrate which may consist of a metal sheet or foil.

Description

Two-dimensional and three-dimensional structures with a pattern identical to that of e.g. cancellous bone

I

Technical field

The present invention relates to a process for producing two- and three-dimensional biocompatible, preferably porous, structures that are suitable for biomedical applications, particularly as a component of prostheses.

Background

In its most general form the invention relates to new basic two-dimensional (2D) structures useful for constructing three-dimensional (3D) structures therefrom, using laminating techniques known per se. The uniqueness of said structures resides in their displaying a pattern identical to that of natural organs and particularly cancellous bone.

The present invention provides further a new process for producing said structures, which process may comprise digital slicing of an object, digital data processing, replicating the digital slices on a substrate and if desired assembling the replicated slices to obtain 3D structures useful as components of prostheses.

Prior art.

To the best of our knowledge no prior art exists pertaining to said unique structures or to the above process for producing such structures, which involves a transfer of technologies known per se, to the production of components of prostheses.

Background art.

The background art pertains to several aspects of the present invention which will be further described below. These aspects will cover the types of materials used for producing structures for biomedical applications, the nature of surfaces/coatings, the production of porous metallic objects for biomedical applications, laminating techniques, photochemical machining (PCM) and photo chemical etching (PCE). The invention will now be discussed further and will be put in the general context of the background art.

The structures according to the invention are preferably constituted from a sheet or foil, preferably from a metal carrying a pattern identical to that of a natural organ such as cancellous bone, said structure being a 2D or a 3D construct constituted from said 2D structures.

The metal is preferably selected from Ti, Ta, Ti6A14V or alloys herefrom although other metals appropriate for medical use could be applied.

The 2D or 3D structures obtained or obtainable according to the process described below can be applied in the production of mass produced or customized components for prostheses.

The process according to the invention for producing a biocompatible, preferably porous structure, preferably made from metal, advantageously comprises: i) Selecting a 3D solid object or a virtual 3D object generated by Computer Aided

Design Software; ii) Digitally slicing said 3D object to obtain digital slices iii) Subjecting said digital slices to digital data processing by editing, engineering and/or other manipulation to achieve expansion, optimisation and/or redesign to comply with predefined biomechanical and/or surgical requirements; iv) Replicating the digital slices on a substrate which may consist of a metal sheet or foil using photo printing techniques such as photochemical etching or photochemical machining; v) If necessary, assembling two or more of the replicated slices to produce a 3D structure, preferably by employing powder metallurgy technique or direct diffusion bonding. In a preferred process according to the invention in step i the selected object is cancellous bone.

In a preferred embodiment of the present invention surface geometrical features of a natural organ, preferably cancellous bone, are incorporated in the digital file (slice). A few words on the metal recommended for use:

Titanium and Tantalum are two most frequently used metals for biomedical implants. Their most general properties are listed in Table 1

Table 1 General properties of Ti and Ta

Pure titanium, pure tantalum and titanium alloys which are considered the best biocompatible metallic implant materials are applied as temporary or permanent implants and prostheses in traumatology, orthopedics and dental surgery. From macroscopic geometric viewpoint, they can be categorized into three groups (1) dense implants; (2) macroporous implants; (3) porous surface layer (coating) on dense implants. Most implants or devices are made in dense form, for example, the hip stem for hip joint replacement. The reports of using bulk macroporous implants alone made of Ti or Ti alloy are limited. On the contrary, many patents and publications are related with the use of a porous coating on dense substrates, e.g. a hip stem or acetabular cup.

The need for developing such porous surface on implants can be explained as follows: taking the hip stem for example, during implantation, the hip stem can be fixed in position with cement (e.g. PMMA) or without any cement, namely cementless hip prosthesis, which enables the prosthetic components to be fixed directly in the osseous bed. A mechanically stable anchorage must be achieved in the prosthesis/bone interlace during the first post-operative weeks to ensure the permanent osseointegration of the implant. The secondary fixation of the prosthesis results through the in- and ongrowth of the new bone on the surface of the implant.

Two kinds of surfaces can be distinguished: bone ingrowth and bone ongrowth surfaces. Bone ingrowth surfaces are characterized by an open porous structure, through which the bone can grow into the structure. This type of surface is also known as "porous coating". Studies have shown that a pore size of 100-400 μm and a porosity volume of 30-50% were best. A bone ongrowth surface is macro- micro-structured by means of suitable process, so that the bone can grow onto the surface. These surfaces are rough, with arithmetical average roughness (Ra) being usually between 4 and 15 μm.

The current invention is based on the following existing techniques: (1) precision machining of metal sheets, including Photo Chemical Etching and Electroforming. (2) lamination technique, that is building 3D structure from 2D sheet or layer; (3) Powder Metallurgy (P/M), this is the technology and art of producing metal powders and of the use of metal powders for the production of massive materials and shaped objects.

Background techniques relevant to the current invention can be put into the following groups:

(1) producing porous metallic objects, especially Ti and Ta, using different geometric strategies: (1) 0D^3D; (2) 1D^3D; (3) 2D^3D (4) 1D^2D^3D; (5) 2D+0D^3D.

(2) photochemical etching of metal sheet into cross-sectional pattern of cancellous bone

(3) digital data processing of cancellous bone, for example, expansion of small volume of bone from micro-CT scan into a clinically relevant dimension, re-engineering of the digital structure of e.g. cancellous bone in dependency of the local biomechanical load situation, the determination of the fractal dimension of natural bone, and the incorporation of such fractal dimension into the engineered digital structure of e.g. cancellous bone. (4) sheet metallurgy of Ti and Ta Background techniques for producing porous metallic objects, especially from Ti and Ta, using different geometric strategies

From the viewpoint of Euclidean geometry, to make 3D porous metal structure, one can start from OD (powder), ID (fiber), 2D(mesh or porous 2D sheet), 3D (solid block and later drilling holes in it), or combination of the above.

With regard to processing technique, to produce a component from metal, conventional processing routes can be followed such as forging, casting and powder metallurgy (P/M). The first two routes are rather difficult for producing a porous structure, so P/M is the preferred choice left. For this reason it is common to start from OD powder, but in that case different pore-generating methods are applied

Strategy 1: OD ^ 3D

Reticulated polyurethane foam is a popular template to start with for producing pores, especially for higher porosity, e.g. higher than 90%. Firstly titanium powder is made into a suspension with low viscosity, namely slurry, then different routes can be used: a positive replication [Ref.l, 2], Ti slurry is coated on the PU foam, drying and sintering is performed to obtain porous Ti foam; few people used negative-negative replication [Ref. 3], or investment casting; and one company [Ref 4] uses electrolytic deposition. Another common P/M technique for making porous Ti is to mix Ti powder with a pore- maker, normally a compound which can be removed under heating, like urea, sodium bicarbonate, PMMA beads etc. [Ref 3,5]

If the organic pore-maker has also the function of foaming, then another group of P/M methods is found to produce porous Ti. [Ref.6]

There exists another variation of the method of Ti powder plus organic pore-maker, wherein an extrusion technique is used to control the final porous structure in a more desirable way [Ref 7]: rods consisting of a shell (Ti powder + binder) and a core (organic filler) are co-extruded, chopped, and re-packed or re-extruded again. Finally all the organic components are removed through pyro lysis and the constructs are sintered.

The pores in porous Ti can be made from organic pore-maker, as listed above, or made from gas alone [Ref 8] (termed also as foaming): argon air is entrapped in a pack of Ti powder under high pressure, and then the releasing argon generates the pores when the constructs are heated at certain temperature where Ti undergoing a superplastic state.

Porous Ti can also be made in a rather simple way: Ti beads (solid or hollow) are packed and sintered [Ref 9], the pores are automatically generated from the interstitial space among the beads, due to its simplicity, this technique was widely used to produce the porous coating on hip stems and on acetabular cups.

Porous Ti can be made from another mature technique: vacuum plasma spraying coating. After a layer of Ti coating is made in such way, porous Ti is obtained by simply cut off from the substrate. [Ref 10]

Also belong to this 0D->3D strategy, several methods of making porous metal from powders by using Rapid Prototyping methods have been developed. Porous titanium was manufacturing by a modified Fused Deposition Modelling method [Ref.11], filaments of titanium powder (containing binder) are deposited onto a platform whose X-Y movement was controlled by computer, after one layer, the platform was lowered along Z direction. Such steps are repeated until a 3D model is formed. The finish steps include debinding and sintering in a high- vacuum furnace.

No prior art related with the rapid prototyping of porous tantalum has been found.

The disadvantages of this technique are:

The starting material is titanium powder, therefore, binder and later debinding process are inevitable. All the organic binders have detrimental effect on the mechanical of Ti parts. Each layer has to be processed separately, the mass production is a challenge.

Another disadvantage of such technique is the lack of accuracy in Z direction. Another recently developed 3D rapid prototype technique of producing 3D porous structure is called Direct Laser Forming: layer information of the original 3D model are obtained, in the production unit, the structure of the respective layer is selectively melted into a powder bed of Ti by a scanning laser beam. After the short exposure to the laser spot, the molten zones quickly solidify. In the next step, the production platform is lowered one layer thickness, a new powder layer is spread and scanned. This process is repeated until a 3D analogue of the original model is obtained. [Ref 12].

Those P/M techniques described above are all initiated from titanium powder, therefore they all face a common technical challenge: to prevent the formation of so-called "alpha-case". In other words, to prevent the reaction between Ti powder and such elements as C, N, and O from air and from any organic components involved in the process, especially O which has a high affinity to Ti. The reason is that such "alpha- case" layer is detrimental to the overall mechanical performance and even raise a problem for regulatory party. The organic components involved, e.g. pore-maker or foaming agent or PU foam, should be either limited to very small quantity, e.g. less than 2 wt.% of total constructs, or can be removed completely below 200 °C.

Porous Ta from strategy of OD ->3D: To our knowledge the only porous tantalum was developed by Implex Corp.,

Hedrocel® [Ref.13]. The porous material is comprised of approximately 99% tantalum and 1% vitreous carbon, by weight. The product is fabricated via a chemical vapor infiltration (CVI) process in which pure tantalum metal is precipitated onto a reticulated vitreous carbon (RVC) skeleton resulting in encasement of the RVC within the tantalum. This material is comprised of 75-85% void space (pore volume) and is characterized by continuous interconnecting pores, or cells, each of which possess the shape of a dodecahedron. The cell size is controlled by the manufacturing process and is nominally 550 mm. The thickness of the struts that define the cells dictates the percentage of void and the strength and stiffness of the bulk material. The tantalum struts are joined together at intersection points, or nodes, with typically three struts intersecting at each node. Strategy 2: ID ^■* 3D

The effort to make 3D porous metal from ID (fiber) has also been made, however the resulting pores are not well defined [Ref 14].

Strategy 3: 2D -> 3D

EP0621018 describes a prosthesis for the replacement of hard tissues of human bones and joints, comprising a porous laminate component of biocompatible sheets with a thickness of less than 150 microns having a plurality of through holes of a diameter ranging from 100- 400 micrometer communicating with each other in the direction of the thickness. The 2D porous sheets are produced by laser cutting.

No prior art was found using 2D metal sheet which has the 2D pattern of cancellous bone.

Strategy 4: ID ^■* 2D ^■* 3D

The most popular method of building 3D porous structure from 2D mesh have been used widely, even in the form of commercial products. For example, the fiber mesh from Zimmer USA and mesh structure from Sulzer Orthopedics, Switzerlands [Ref 3]. Geometrically, the basic building unit is ID fiber rather than 2D mesh.

US4636219 describes a process for producing a biocompatible mesh screen structure suitable for bonding to a prosthetic substrate. Said process comprises producing a stack of 4-8 layers of mesh from Titanium or alloys therefrom, particularly Ti6A14V, heating the stack at a temperature ranging from 1650-1725F and a pressure of 130-1500 psi for 12-24 hours. Each layer of the structure is biased with an angle of 45 degrees with respect to its neighbouring layers. The structure obtained can be bound to the body of a prosthesis by any welding technique known per se. French patent application 8713062 (publication number 2620623) describes a porous structure for bone repair consisting of at least 2 layers of a woven material from a metal which can be welded. The structure can be applied onto a prosthesis.

The techniques described above share two common features: (1) the basic structural units are metal mesh, fibrous material, grids or screen etc, none of them has the 2D pattern of cancellous bone (2) those units are bonded together through either diffusion bonding or spot welding. Therefore, the final constructs have certain disadvantage like too many joints between those fibers, and such joints are detrimental to mechanical strength and especially to fatigue strength of the constructs.

Strategy 5: 2D+0D -> 3D

International patent application PCT/NL2005/00050 discloses one technique of making porous metal parts from both powder and perforated porous sheets with a relief pattern. The powders used here have two fold iunctions: to improve the bonding between adjacent sheets by increasing the contact area and to improve the overall surface roughness. The roughness parameter of Ra is located in the range of 4-15 micron.

(2) background art relevant to photochemical etching of a metal sheet into cross- sectional pattern of cancellous bone

Photo Chemical Etching is an engineering production technique for the manufacture of burr free and stress free flat metal components by selective chemical etching through a photographically produced mask, also termed maskant, photomask or phototool.

No publication and patents was found relating to the use of photochemical etching to generate the 2D metal sheet with the pattern of cancellous bone of human or animals destined to the production of prostheses.

(3) Digital data processing of cancellous bone, for example, the determination of the fractal dimension of natural bone, expansion of small volume of bone from micro-CT scan into clinical implant relevant dimension, re-engineering of the structure of cancellous bone according to the local biomechanical load situation The means of acquiring digital slices of e.g. natural cancellous bone include X-ray radiography, MRI, computer tomography (CT) and micro-CT. Among them, micro-CT can have the highest resolution. With the progress of each technology mentioned above, the volume of natural bone that can be processed is increased continuously. The volume difference between a micro-CT scanning sample and a typical medical device is large. No prior arts was found that teaches how to expand a small piece of cancellous bone structure into unlimited volume. Also, no prior art was found describing how to re-engineer the natural cancellous bone structure with to enhance its applicability in medical devices, e.g. to accommodate to the local biomedical and surgical situation where the device will be implanted.

(4) background art relevant to sheet metallurgy of Ti and Ta

Fiber metallurgy offers several advantages over powder methods. At a given porosity, fiber-derived materials are superior to powder-processed analogs in strength and impact resistance [Ref.15]. It is logical to assume that sheet metallurgy may have some advantages over fiber metallurgy.

The objectives of the present invention can be summarised as follows:

A principal object of the present invention is to produce a biocompatible 3D porous metallic structure (preferably made from Titanium, Ti6A14V or Tantalum). The structure can be

(1) An authentic copy of (human or animal) cancellous bone

(2) or an engineered copy (e.g. expanded) of (human or animal) cancellous bone (3) or a specifically designed structure of cancellous bone according the requirement of the surgeon and the local biomechanical situation.

Another object of the present invention is the production of a 3D porous structure starting with the manufacturing of high precision 2D metal sheets with a pattern that is identical to a digital slice of an organ, preferably cancellous bone. Another object of the present invention is to provide metal sheets with a pattern of e.g. cancellous bone by applying photochemical etching, electroforming as means for achieving replication.

Another object of the present invention is to provide a unique digital processing technique of expanding a small piece of an organ, especially cancellous bone, into a larger digital image of the organ along X, Y and Z axis by using the so called 'mirror- flipping' method.

Another object of the present invention is to achieve that all the geometric parameters of the porous structure can be designed and controlled with high accuracy (up to 0.1 micron) during manufacturing, including pore size, shape, porosity, interconnectivity, fenestration sizes, surface roughness of the inner surface of pores, even hierarchical structure across a wide range, particularly the micro-texture of the inner pores, for example, to the level of designed (local or global) fractal dimension of the porous body.

Another object of the present invention is to provide a reconstruction technique (1) by using powder as adhesive, in detail, each cancellous sheet of metal will be first coated overall with a layer of metal powder, then powder metallurgy is used to fuse the 2D sheets (similar to prepreg in fiber reinforced composite industry) into 3D construct. (2) by using direct fusion bonding, due to the excellent finish condition of photochemical etching and the relative large overlap area between adjacent sheets, those 2D sheets can be bound via direct diffusion in the sintering furnace (under appropriate temperature and pressure).

Detailed description of the invention

For the production of the 3D implant structure according to the invention sheets are produced from a biocompatible material. Biocompatible materials are well known in the art and are described and defined in e.g. D.F. Williams "Progress in biomaterial engineering, 4 definitions in Biomaterials" 1987 Elsevier. Although many ductile materials can be used in the present invention such as metals including titanium, titanium alloys, cobalt alloys, tantalum and its alloys, niobium and its alloys, zirconium, we prefer to use the above mentioned metals and particularly titanium, tantalum or alloys thereof and particularly Ti6A14V. Also cobalt-chrome alloys and chrome-cobalt-molybdenum alloys are very suitable.

The present invention provides a process for producing a biocompatible structure carrying a pattern identical to that of a natural tissue such as cancellous bone, said structure preferably being made from metal, which process comprises replicating an image of the natural tissue on a substrate which may consist of a metal sheet or foil.

In a particular embodiment, the whole process starting from e.g. digital imaging of human or animal organ, especially cancellous bone can be summarised as follows: first a piece of cancellous bone to be copied is chosen; next 2D digital slices of such piece of bone are acquired through micro-CT scanning; then those digital slices files are subsequently manipulated to make available larger sizes. To do so, each digital slice needs to be firstly copied and then the copied image is flipped along both X and Y direction, such steps being repeated until the desired dimension is available; then such images (e.g. in the format of BMP) are converted into DXF format, following which the so-called photochemical etching procedure can start.

First a so-called photomask should be made by a high-resolution plotter (up to 10,000 dpi). Such photomask (template) is a positive or negative replica of the 2D digital slice of the organ, especially cancellous bone, depending on the resin used which can be photosensitive or photo-resist.

Dense metal sheets are to be cleaned chemically-^ photo-sensitive resin is coated to both top and bottom surfaces -> (engineered) 2D cancellous bone image is transferred onto the photo-sensitive resin by UV exposure -> then processing of the resin starts: developing, rinsing, and drying -> the metal area not protected by the resin can be removed by etching -> the left photo-sensitive resin is removed and 2D metal copy of the 2D digital slice of the organ, especially cancellous bone, is ready.

It should be noted that the whole process can also be started from a virtual bone structure generated from computer software like AutoCAD. The last step is the reconstruction of the 3D porous structure from 2D metal sheets with the pattern of the organ. There are two technical routes: one is the combination of powder metallurgy and sheet metallurgy and the other is sheet metallurgy alone, in other words, those 2D sheets can be bound with or without metal powder.

Route with powder (Strategy: 2D+0D^3D):

2D metal sheets with the pattern of e.g. cancellous bone are covered with a layer of metal powder as coating, next a 3D structure is constructed. The whole construct is put in a furnace and subjected to a treatment to remove binding agent and to achieve sintering. Although the quantity of binding agent used is extremely low, care needs to be taken during the removal of the binding agent because of the high reactivity of titanium powder. By using this route, the overall surface of the 3D construct will be roughened by the powders, besides achieving the designed surface geometry in the digital slices.

Route without powder (Strategy: 2D->3D):

If the digital slice is not too thick so that the adjacent metal sheets with the pattern of an organ can share a certain level of overlapping areas, because the photochemical etching is a blur- free, internal stress free process, direct diffusion bonding can be achieved if the sintering is performed under appropriate temperature and pressure. By using this route and by choosing a good combination of several parameters, the surface geometry in the digital slices can be controlled to a very precise level, much finer than any other processing techniques for making porous metals described in the above resume of the prior art.

The sintering conditions will depend on the material used. In case the preferred biocompatible metals are used i.e. titanium, tantalum or alloys thereof as herein before defined, the temperature will range from about 1100 °C - 2000 °C. Heating is carried out at in high vacuum preferably at a pressure of 10 (minus 5) millibar, for at least 1 hour and preferably 2-5 hours. Sintering is carried out in a vacuum furnace under an atmosphere of helium or argon. For the purpose of biomedical application, the sheets in the present invention having a thickness varying from 50-1000, preferably 100-200 microns are suitable.

The 3D, biocompatible implant structures according to the invention and obtainable according to the process hereinbefore described and defined, have a highly porous structure predominantly consisting of interconnected open pores of suitable size distribution, and consist of a sintered stack of sheets of ductile biocompatible material, virtually free from nodes or welding points, resulting in an improved mechanical strength.

The invention will now be illustrated in the following examples.

Example 1.

Commercially available sheets of tantalum with a thickness of 100 micrometer

(0.1 mm) were purchased.

Cancellous bone from the condyle of a sheep was used as a model. A digital building unit block (5x5x5 mm) was generated from a series of micro-CT scanning images (digital slices). One of these digital slices is shown in Fig. 1.

After engineering, this slice is expanded to 70x70 mm. A porous tantalum based structure, resembling natural cancellous bone structure, is produced by replicating the digital slices in tantalum sheets through direct fusion bonding method.

Example 2

Commercially available sheets of titanium with a thickness of 100 micrometer (0.1 mm) were purchased. Cancellous bone from a human femur head was used as a model. A digital building unit block (5x5x5 mm) was generated from a series of micro-CT scanning images. After engineering, all the slices were expanded by mirror-flipping to 60x60 mm. The production process of a titanium sheet with cancellous bone structure is explained as follows:

(1) the image with the dimension of 60x60 mm was used to design and to make photomask, (2) the Titanium sheet was degreased and cleaned with normal method,

(3) photoresist was coated onto both sides of the Ti sheet

(4) the Ti sheet was put in the photomask and underwent UV light exposure

(5) the exposed Ti sheet was developed to remove non-cured photoresist

(6) the Ti sheet was subjected to etching to generate pores in it (7) the rest photoresist was removed and the Ti sheet was cleaned

The final product is depicted in Fig.2

Example 3

A 3D engineered copy of the original cancellous bone was made with the dimension of 60x60x60 mm, using titanium sheets obtained by the methodology described in Example 2. The sheets were stacked and brought in a vacuum furnace for sintering at 1300°C under a pressure of lower than about 10 minus 5 millibar for 3 hours. Two different views of the structures so obtained are depicted in figures 3 and 4.

Example 4

An acetabular cup was made using titanium sheets obtained by the methodology described in Example 2. The sheets were stacked after preshaping and fixated. The result is depicted in Fig. 5.

Next, the fixated structure was sintered in a furnace.

Example 5

Example 4 was repeated, except that only selected parts of the titanium sheets were etched to reproduce the cancellous bone structure. In the non-etched parts of the sheets, holes were drilled in predefined locations. These holes can suitably be used for fixating the stacked sheets after etching. A single sheet that is to form a 2D layer of an acetabular cup is shown in Fig.6.

References

I. J.P. Li, S.H. Li, K. de Groot, and P. Layrolle, Preparation and characterization of Porous Titanium, Key Engineering Materials VoIs 218-220 (2002) p51-54. 2. Commercial products information from www.astromet.com/200.htm and www.porvairfuelcells.com 3. Markus Windier, RaIf Klabunde, Titanium for Hip and Knee prostheses, from book: Titanium in Medicine, edited by D.M. Brunette, P. Tengvall, M. Textor, P. Thomsen, Springer, 2001, P726 4. Reade Advanced materials

(http://www.reade.com/Products/Foam/foam-metal.html)

5. M. Bram, C. Stiller, H.P. Buchkremer, D. Stover, H. Bauer, Preparation and characterization of high-porosity titanium, stainless steel, and superalloy parts, from Metal foams and porous metal structures, edited by J. Banhart, M.F. Ashby, and N.A. Fleck, MIT Verlag (1999) P.197-202

6. Maxime Gauthier, National Research Council Canada, presentation on ASM Materials & Processes for Medical Devices Conference, Sept 8-10, Anaheim, California, USA

7. L. Tuchinskiy and R. Loutfy, Novel process for cellular materials with oriented structure, from Metal foams and porous metal structures, edited by J. Banhart,

M.F. Ashby, and N.A. Fleck, MIT Verlag (1999)

8. D.C. Dunand, J. Teisen, Superpastic foaming of titanium and Ti-6A1-4V, Mat. Res.Soc. Symp. Proc. Vol. 521 1998

9. Pilliar, R.M., Overview of surface variability of metallic endosseous dental implants: textured and porous surface- structured designs. Implant Dent, 1998.

7(4): p. 305-14.

10. S. Fujibayashi, M. Neo, H. Kim, T. Kokubo, T. Nakamura, Osteoinduction of porous bioactive titanium metal, Biomaterials, 2003

I 1. J.P. Li, informal communication, Bilthoven, the Netherlands, 2004. 12. D. A. Hollander et al. Structural, mechanical and in vitro characterization of individually structured Ti-6A1-4V produced by direct laser forming, Biomaterials 2006 Mar 24(7) 955-63. 13. Zardiackas LD, parsell DE, Dillon LD, Mitchell DW, Nunnery LA, Poggie R, J. Biomed. Mater. Res. 58(2): 180-187, 2001

14. Product from Zimmer Japan (Tokyo, Japan), scientific publication appeared at N. Murakami, N. Saito, H. Horiuchi, T. Okada, K. Nozaki, K. Takaoka, Repair of segmental defects in rabbit humeri with titanium fiber mesh chlinders containing recombinant human bone morphogenetic protein-2 (rhBMP-2) and a synthetic polymer, J. Biomed. Mater. Res. 62(2): 169-174, 2002.

15. Vladimir Shapovalov, MRS Bulletin, Apr. 1994, 24-28.

Claims

I) A structure, preferably constituted from one or more sheets or foils, preferably made from a metal, said structure carrying a pattern identical to that of a natural tissue such as cancellous bone, said structure being a two-dimensional (2D) or a three-dimensional (3D) construct.

2) A structure according to claim 1 wherein the metal is selected from Ti, Ta, Ti6A14V or alloys therefrom.

3) Use of 2D and 3D structures according to claim 1 or 2 in biomedical applications as a mass produced or customized component of prostheses.

4) Prostheses comprising 2D or 3D structures according to claim 1 or 2.

5) A process for producing a biocompatible, preferably porous, structure carrying a pattern identical to that of a natural tissue such as cancellous bone, said structure preferably being made from metal, which process comprises replicating an image of the natural tissue on a substrate which may consist of a metal sheet or foil.

6) A process according to claims 5, comprising: i) Selecting a 3D solid object or a virtual 3D object generated by Computer Aided

Design Software; ii) Digitally slicing said 3D object to obtain digital slices iii) Subjecting said digital slices to digital data processing by editing, engineering and/or other manipulation to achieve expansion, optimisation and/or redesign to comply with predefined biomechanical and/or surgical requirements; iv) Replicating the digital slices on the substrate using photo printing techniques such as photochemical etching or photochemical machining; v) If necessary, assembling two or more of the replicated slices to produce a 3D structure, preferably by employing powder metallurgy technique or direct diffusion bonding. 7) A process according to claim 6, wherein in step 1 the 3D solid object is cancellous bone.

8) A process according to any one of claims 5-7,wherein the substrate consists of Ti, Ta, Ti6A14V or an alloy thereof.

9) A process according to any one of claims 6-8, wherein the surface geometrical features of a natural tissue, preferably cancellous bone, are reflected in the digital slices.

10) A process according to claim 9, wherein the surface geometrical features reflected in the digital slices are the fractal dimensions of natural bone.

H) A process according to any one of claims 6-10, wherein digital slices of the 3D solid object are produced using computed tomography or X ray radiography.

12) A process according to any one of claims 6-11, wherein the digital slices are converted in to vector format following digital data processing.

13) Biocompatible structure obtained or obtainable through a process according to anyone of the preceding claims 5-12.