WO2009022911A2

WO2009022911A2 - Prosthesis comprising an anti-micromotion bone-interfacing surface and method for the manufacture thereof

Info

Publication number: WO2009022911A2
Application number: PCT/NL2008/050551
Authority: WO
Inventors: Shihong Li
Original assignee: Cam Implants B.V.
Priority date: 2007-08-16
Filing date: 2008-08-18
Publication date: 2009-02-19
Also published as: WO2009022911A3

Abstract

The present invention relates to a prosthetic implant for the replacement of hard tissues of bones or joints that provides improved initial fixation to the bone or joint substrate. A t least a part of the outside of said implant is composed of a biocompatible construct, wherein at least a part of the exterior of the construct that is used to attach the implant to bone or joint consists of a curved or planar surface carrying a plurality of protruding parts each characterized by a height of 10 - 1000 ¼m and a maximum diameter of 10 - 1000 ¼m, said protruding parts being characterised in that they are sufficiently sharp to penetrate bone; and wherein the surface of the construct that is used to attach the implant to bone or joint has a total in - plane projection area of at least 1 cm 2 and contains at least 50 of the aforementioned protruding parts per cm 2.

Description

PROSTHESIS COMPRISING AN ANTI-MICROMOTION BONE-INTERFACING SURFACE AND METHOD FOR THE MANUFACTURE THEREOF

TECHNICAL FIELD OF THE INVENTION

The present invention relates to orthopedic materials, and more particularly to prosthetic implants for the replacement of hard tissues of bones or joints, and even more particularly to uncemented (cementless) prosthetic implants.

Also provided is a method for the manufacture of such prosthetic implants.

BACKGROUND OF THE INVENTION

Biocompatible materials with high durability are of interest to orthopedic implant manufacturers. For prosthetic implants to take over the function of the piece of bone that it replaces it is crucial that the implant remains firmly fixed to the accommodating bone over its entire service life span. The ideal situation is that no relative movement occurs at all. Nevertheless, in clinical practice, some very small amplitude motion (micro -motion) is tolerated, even though preferably even micro- motion should be avoided. In case the micro-motion exceeds a certain threshold value, fibrous tissue instead of the desired bone tissue will grow around the implant. Once fibrous tissue has been formed around the implant, new bone tissue cannot grow there. Since the fibrous tissue will not turn into bone tissue, the consequence is that no firm bond is established between bone and implant. Due to the obvious importance of fixation, it is used to categorize prosthetic implants as cemented or uncemented (cementless), the distinction being based on the way fixation is achieved.

Cement here refers to a polymer, polymethylmethacrylate (PMMA), which behaves very much like Portland cement in the way of hardening: a powder is mixed with a liquid to form a paste which hardens after a few minutes. In clinical practice, freshly reamed cancellous and/or cortical bone is exposed and cleaned, PMMA cement is put in the site, and then the implant is inserted in such paste. After hardening, PMMA functions as grout and fixation is achieved. Uncemented porous implants offer the advantage that bone tissue can grow into the porous surface of the implant and hence a biological fixation is achieved over time through bone/porous implant interlocking. The fixation of implants onto bone can be divided into four stages:

(1) initial (immediately after operation);

(2) short term (up to 5 years);

(3) intermediate term (up to 10 years);

(4) long term (up to 15 years and beyond). Both cemented and uncemented implants have challenges of loosening their fixation during service, resulting in malfunction of the implant. However, such risks appear in different time periods depending on the fixation type. As can readily be understood and as confirmed by many scientific publications, long term fixation for cemented implants is challenging; while initial fixation is more difficult for uncemented ones.

It is well-accepted that initial fixation is critical for long term fixation. For uncemented porous implants, it should be noticed that the abovementioned four stages of fixation have different mechanism: initial fixation is achieved through (static) friction while the other fixation stages are dependent on interdigitation between ingrown bone tissue and porous implant.

Depending on the fixation mechanism used, porous implants can be regarded as consisting of two main parts: bone-interfacing surface and bone-ingrowth region. The requirements for both the bone-interfacing surface and the bone-ingrowth region are summarized in the following table.

Table: Comparison of bone-interfacing surface and bone-ingrowth region

Bone-interfacing surface Bone-ingrowth region

Definition The external surface of an implant The external surface except for bone- supposed to contact with bone or interfacing surface and all the porous joint space enclosed within the implant

Function Initial fixation Later fixation during the service life

Gateway of bone-ingrowth span

Fixation through (Static) friction Interdigitation between ingrown bone tissue and porous implant

Geometric requirement Porous determined by its function as Porous bone-ingrowth gateway High Specific Surface Area and high

As much contact area with adjunctive permeability bone as possible

It is clear from this table that the functional and geometric requirements for bone-interfacing surface and bone-ingrowth region are quite different. As explained herein before, initial implant stability is critical for successful osseointegration. During the past 4 decades, many efforts have been made to achieve initial implant stability. The techniques developed to achieve this can be categorized into 'structural design' and 'surface design'.

Structural design techniques make use of macroscopic features to achieve fixation. Taking the acetabular cup as example, examples of such macroscopic features include dome screws, peripheral screws, peripheral threads, dome spikes, peripheral fins, and insertion with a press-fit technique in which the component is oversized compared with the diameter of the prepared acetabulum. Macroscopic features applied to the hip stem include tapered design and stem with collar. These features can be categorized as macroscopic since the scale of the designed feature (spike, fin, taper, collar etc.) is large, e.g. larger than the pore size of cancellous bone. It is easy to understand that these macroscopic measures assert their effect only within limited regions. For example, the dome screw can pull the acetabular cup to the bony site, but it hardly affects the rim region or may even adversely affect fixation at rim region. The total number of spikes is always limited, and their functions have been shown to be limited to local areas. Press-fit techniques improve the fixation in rim region, but often at the cost of fixation in the dome region. (AAOS: Hip and Knee Reconstruction 3, Hip designs, P. 352).

So far surface design techniques have employed three different strategies: (a) adding extra material to form a porous surface;

(b) removing material to form a porous surface;

(c) direct forming of a porous surface. An example of a surface design techniques in which a porous surface is created by adding extra material is the application of a porous metal coating (sintered beads, sintered wire) onto substrate metal implants. Sintered porous-coated implants were developed in the early 1970s with human clinical use commencing in the late 1970s and increasing throughout the 1980s. (RM Pilliar, Orthop Clin N Am, 2005, 36(1), 113-9). The original idea was to (a) introduce rough surface (b) increase the specific surface area (SSA) and (3) introduce interconnected porous structure to facilitate the ingrowth of vascular system and bone tissue. Another type of adding method generating smaller pore size is plasma-spray titanium coating. An example of a porous implant that is manufactured through a surface design technique that creates porosity by removing material is the product Tecotex® from Tecomet. The surfaces of these metal implants have been selectively etched off to produce recessions.

Surface design techniques that enable direct formation of a porous implant have also been made available. For instance, porous Co-Cr-Mo alloy surfaces have been made through an innovative direct casting technique. The porous surface has three- dimensional interconnected openings for bone ingrowth.

The aforementioned surface design techniques have focused mainly on providing porous implants with optimum bone-ingrowth properties. However, so far little attention has been paid to optimizing the initial fixation of the implant. The present invention aims to provide prosthetic implants that exhibit improved initial fixation as well as a new surface design technique for the manufacture of such improved implants.

WO 02/069851 discloses ordered repeating micro -geometric patterns on orthopaedic implants to effect enhanced a direct adhesion to tissue and osseo- integration of an implant to bone. A multiplicity of ridges and grooves is provided each having a width and depth in the range of 2.0 to 25 μm. The micro geometric repetitive patterns define a guide for preferential promotion of rate, orientation and direction of growth colonies of cells of the bone. It has been found that the known micro-scale protrusions are suitable for influencing cell proliferation but fail to enhance initial fixation. In EP 0 827 726 a structured bone-contacting surface of an implant is described in which a multiplicity of cylindrical bores with a diameter of 300 -1000 μm is and which have a maximum height of 1000 μm. The number of protrusions per cm and their flat top surface nature result in a bone contacting surface which is such that insufficient bone penetration occurs when the surface of the prosthetic implant approaches the bone, such that this results in sub optimal initial fixation.

In EP 1 062 956 an orthopaedic implant is described that is formed by application of a coating of bioreactive material such as hydroxyapatite that is applied onto the metal surface of the implant. The coated material comprises protrusions of a maximum height of 150 μm which is polished to form micro cavities with a maximum length of 400 μm and a minimum height preferably higher than 20 μm. The coated material is relatively soft and the shape of the polished micro protrusions is blunt such that an optimal initial bone fixation is not achieved.

In US 4,608,052 an implant for use in a human body is disclosed having an integral attachment surface adapted to permit tissue ingrowth. Intersecting, generally aligned rims define an inner attachment surface portion from which a multiplicity of posts project. The posts may have a width of about 440 μm and a bore depth of about 500 μm. The blunt shape and number of posts per cm-1 do not result in sufficient static friction upon contact of the structured surface with a bone structure and hence fails to provide a sufficient degree of initial bone fixation. Furthermore, all protrusions are oriented substantially perpendicular to the surface of the implant, such that micro motions with a component along the bone contacting surface are not sufficiently counteracted.

From WO2006/091097 in the name of the applicant it is known to construct a three-dimensional porous construct for use in implants having a bone-contacting surface, from a multiplicity of two-dimensional apertured sheets of a bio compatible material, such as tantalum or titanium, that are interconnected to form a porous three- dimensional structure. These structures provide improved bone ingrowth and good fixation in a later stage after application. The known structures however fail to show any protrusions and can be improved to provide a better initial fixation of the bone- contacting surface.

DEFINITIONS

For a better understanding of the present invention, the following definitions are provided:

The term "implant" refers to any device that is placed or designed to be placed inside the human or animal body. The term "pyramidal-shaped" means a three-dimensional shape drawn up from a polygon base surface having planes extending form each side of the base surface to a common upper edge or to a common apex. The planes may comprise surface irregularities.

The term "porous" as used herein in relation to the implant means that at least a part of the implant is porous, notably the part of the implant that will be interfacing with bone or joint. Thus, the porous implants in accordance with the present invention also encompasses implants comprising parts that are non-porous.

The term "porosity" refers to a property of a material defined by: 100 x (Vapparent - V_actuai) / V apparent, wherein V_apparent represents the apparent volume of the material and V_actuai the actual volume.

The term "macro -scale" is used to refer to features having a size in the range of 1000 to 2000 μm.

The term "micro-scale" refers to the scale of a few micron or sub-micron scales, which is corresponding to the machined (mechanically of chemically) surface feature located in the range less than 50 μm.

The term "meso -scale" refers to the scale between "micro scale" and "micro scale" defined above. In the present invention, meso-scale is used to refer to features having a size in the range of 50 to 1000 μm. The term "bone in-growth" refers to the ability of newly formed bone tissue to penetrate an implanted open porous structure or the external surface of a solid implant. The term "bone on-growth" refers to the ability of newly formed bone tissue to adhere to the internal surface of an implanted open porous structure. The term "bone-interfacing surface" refers to the external surface of an implant that is designed to contact with bone or joint.

The term "bone-ingrowth region" refers to all the rest surfaces (except bone- interfacing surface) and all the porous space enclosed The term "cell shape" refers to the morphology, shape, size and orientation of the pores in a material.

The term "strut" refers to the structural members, such as rods, beams, plates, shells or columns, which together define the face or edge of a cell within a porous, e.g. cellular solid material. The term "core boundary" refers to the median line of the struts of a 2D digital slice of a cancellous bone and of its biomimetic replica in biomaterials. It will turn into "core meshwork" when several layers of such "core boundary" are stacked into a 3D structure.

The term "contour boundary" refers to the contour boundaries of the struts of a 2D digital slice of a natural cancellous bone or engineered biomimetic structure. It will turn into "contour surface" when several layers of such "contour boundary" are stacked into a 3D structure.

The term "diffusion bonding" refers to joining of materials through application of heat and pressure without causing a phase change in either of the materials, and without the use of a filler material.

The term "roughness" (= micro -roughness) refers to surface irregularities that are manifest on a micro-scale level. See Bharat Bhushan, B. K. Gupta, HANDBOOK OF TRIBOLOGY: Materials, coatings, and Surface Treatments (1991), Page 3.5

The term "waviness" (or macro -roughness) refers to surface irregularities that are manifest on a meso-scale level. See Bharat Bhushan, B. K. Gupta, HANDBOOK OF TRIBOLOGY: Materials, coatings, and Surface Treatments (1991), Page 3.5

The term "cut-off refers to a filter and is used as a means of separating or filtering the wavelengths on a surface. Cut-offs have a numerical value that when selected will reduce or remove the surface features with a wavelength below or above said numerical value. In the context of the present invention, the boundary cut-off between roughness and waviness is 50 μm.

The following terms are used in the description of the protrusion (or pyramids): The term "protrusion" refers to solid three-dimensional (3D) objects. They stand on either solid external surface of an implant or the solid struts of the porous coating layer covering the underneath solid implant. Accordingly, the base carrying those protrusions is termed as the "planar or curved surface". A series of protrusion form a protrusion array. In the present application, all the protrusion (pyramids) in the same array may share the same or similar pyramid direction (e.g. ± 10°). The term protrusion, protruding part and pyramid are used exchangeably in this application.

In case such protrusion array forms a "ratchet", then we can determine a specific direction to it, to assign a "vector" feature to it.

Such vector pyramid array can be described more clearly by using another virtual plane. Such a plane meets two conditions: (1) It is vertical to the local base surface and (2) Such plane is parallel to the array direction.

This virtual plane will be referred to hereafter as "eαth^'ru; plinc .

When the pyramid array and valley between those pyramids is cut with this cutting plane, one gets a continuous 2D curve (or ?.O c*5*tin*> pκn\le). Such 2D cutting profile is termed as "wavincss". Since there is a direction that can be identified for such pyramid array like the example of ratchet, this is termed "S oi ior v. as υvv^. It is of critical importance to distinguish the concept of "vector waviness" from the well- known scalar parameter of roughness in the prior art.

If such cutting action is repeated so that every part of the pyramid is cut and a we call it ",^;π spaisaJ

If the cutting plane is used to cut only one pyramid together with the valley next to it along the array direction, then the 2D profile we got is called one "v\ ;_*\ v iVim \

The term "ratchet" is used herein to describe a plurality of protuding parts that together preferentially restricts motion in one particular direction.

SUMMARY OF THE INVENTION

The prosthetic implant of the present invention offers the advantage that it provides excellent initial fixation through adding protrusions meeting specific conditions onto the bone-contacting surface of the implants. The protrusions stand either directly onto the solid external surface of an implant or on the solid struts of the porous coating layer covering the underlying solid metal implant. Taking into consideration that bone is viscoelastic by nature, the effect of improving initial fixation against bone is even more profound compared to known prior art methods of fixation.

As will be explained below, the improved initial fixation of the present implant is achieved by maximizing static friction at the implant-bone interface.

Static friction is the main mechanism for initial fixation of uncemented implants. However, the conditions for fixation through static frictions are far from optimal, especially in the case of porous implants. This may be explained as follows:

Friction is the force (measured in Newtons) that opposes the relative motion or tendency toward such motion of two surfaces in contact. The two basic laws of friction are:

(1) the frictional force F is proportional to the load or normal force N holding the two surfaces together

(2) F is independent of the apparent macroscopic area of contact between the two surfaces. It is expressed as: F = μN, where N is the normal force holding two surfaces together and μ is called coefficient of friction.

The second law holds for most macroscopic objects. However, for very small objects another friction law has been proposed, published by Coulomb (D. Dowson, History of Tribology. Longman, New York, 1979): (3) F = μN + cA, where c is a constant and A is the real contact area.

The reason why Coulomb's law is applicable for very small objects is that for such objects the parameter A (real contact area) is not negligible. The real contact area between macroscopic bodies is usually extremely limited, and this can be explained as follows: The geometrical texture of the surface is controlled by the characteristics of the finishing process by which they are produced. For example, a smooth metal surface looks macroscopically almost like a mirror. The same surface viewed microscopically is not smooth and contains surface irregularities called asperities. It is these asperities that define the contact area with another object. Thus, it will be understood that the real contact area A of a (seemingly) smooth metal surface is much smaller than the apparent contact area.

The inventor has hypothesized that it may be possible to increase static friction between a prosthetic implant and the bone substrate onto which it is placed by increasing the real contact area A. To realize maximum friction between the bone- interfacing surface of a prosthetic implant and bone, the ideal set-up is: (1) dense bone versus solid implant; (2) intimate and conformal contact between bone and metal across the full interface; (3) interfacing surfaces match even to atomic level, this is called "commensurate" surfaces. However, instead the practical set-up is: (1) porous bone versus optionally porous implant; (2) contact area is defined by asperities from both implant and bone; (3) interfacing surfaces of implant and bone are always incommensurate .

As regards (1), it is noted that some prosthetic implants have to be porous in order to accommodate bone ingrowth and that (cancellous) bone is porous by nature. Furthermore, as long as the implant is made of a different material than bone, the interfacing surfaces will always be incommensurate (3). Thus, since it is essentially impossible to manipulate the aforementioned features (1) and (3), the inventor has focused on enlarging the contact area between implant and bone (2).

The inventor has found that initial fixation of prosthetic implants can be enhanced substantially by introducing many meso-scale protrusions on the bone-interfacing surface. Although the inventor does not wish to be bound by theory, it is believed that the improved fixation is associated with the fact that the protrusions effectively enlarge the real contact area between implant surface and bone surface. In addition, since after fixation of the implant onto the bone many of these protrusions will have penetrated into pores of the bone structure, micro-motion may be inhibited because lateral movement will bring several of these protrusions in contact with the walls of these pores. Another characteristic feature of the protrusions resides in the fact that the top of the protrusion is sufficiently 'sharp' to penetrate bone. Thus, the protrusions may be 'nailed' into the bone to provide fixation, but also to enable further protrusions to enter bone pores, thereby enhancing the overall fixation effect.

The contribution of the meso-scale protrusions to initial fixation was found to be much larger than the contribution from either micro -scale roughness or macro -scale designed features, such as spikes or fins.

The meso-scale protruding parts of the present prosthetic implant have a height of 50-1000 μm and a maximum diameter of 20-1000 μm. Furthermore, the surface of the implant that is used to attach the implant to bone or joint contains at least 50 of these protruding parts per cm². The present invention can be realized through a number of processing techniques, including both conventional and non conventional machining techniques. The conventional machining techniques are mainly used directly on the solid implant surface such as milling and grinding etc. The non conventional machining techniques are mainly used to produce pyramidal-shaped protrusions on porous coatings on solid implants including (photo) chemical etching, electroforming, plasma etching, ultrasonic machining, water jet cutting, laser cutting, electric discharge machining and electron beam machining. The present inventor believes that the lamination method described below is particularly suitable for the joined manufacture of protrusions and the porous coating underneath.

This lamination method is employed to manufacture a porous construct that is composed of two or more thin sheets made of a biocompatible material, each sheet comprising a plurality of through openings and having a thickness of 10-1000 μm, said thin sheets exhibiting a porosity of 20-99%, wherein the method comprises: - preparing two or more thin sheets of biocompatible material, each sheet comprising a plurality of through openings, having a thickness of 10-1000 μm and exhibiting a porosity of 20-99%, wherein the edge of said two or more sheets and/or the rims of said through openings carry a plurality of protrusions having a height of 10-1000 μm and a width of 10-1000 μm; - stacking the sheets of biocompatible material to produce a three-dimensional porous construct; and - binding the stacked sheets

BRIEF DESCRIPTION OF THE FIGURES AND DRAWINGS

Fig 1. shows a schematic representation of a cross-sectional view of an implant in which tapered protrusions have been provided on a solid metal surface,

Fig. 2 shows a schematic representation cross-sectional view of an implant in which tapered protrusions have been provided onto the solid struts of a porous coating that has been applied to the metal surface, Fig 3a represents a micro CT image of human cancellous bone (5x5 mm).

Fig. 3b shows the same image as Fig. 3a after said image has undergone a digital clean-up.

Fig. 4a depicts an enlarged detail of the imaged bone lattice shown in Fig. 3b.

(1.5x1.5 mm).

Fig.4b shows the boundaries and median line of the core meshwork of the imaged bone lattice of Fig. 4a.

Fig. 4c shows the core meshwork and a weak and strong strut region in the original bone lattice.

Fig. 4d shows the outlines of the opening of the imaged bone lattice of Fig.4a.

Fig. 4e shows how the outlines of openings are manipulated by the addition of contour features.

Fig. 5 shows the off-plane protrusions which can be created from in-plane protrusions in a thin sheet of metal through a (micro) embossing process (5x5 mm).

Fig. 6 illustrates the digital stack of five sheets revealing the anti-micro motion bone- interfacing surface equipped with vector waviness in the second generation protrusions.

Fig. 7a-7h show examples of engineered images in which contour features (protrusions and/or indentations) have been introduced.(5x5 mm).

Fig 8 shows one titanium sheet that was obtained by replicating one of the engineered images to which triangle protrusion had been introduced (5x5 mm).

Fig. 9a shows a three-dimensional digital stack illustrating the bone-ingrowth region equipped with vector waviness formed by protrusions.

Fig. 9b depicts a spatial ratchet formed by coordinating the waveforms (protrusions) in the adjacent sheets with gradient dimension change. Fig. 10 shows a non-porous construct comprising a surface that carries a plurality of protruding parts.

Fig. 11 shows a perspective view of the outer surface of an preform for an acetabular cup according to the invention formed by intersecting machined grooves on a spherical metal surface, and

Fig. 12 shows a side view of the preform of fig. 11.

DETAILED DESCRIPTION OF THE INVENTION

Accordingly, one aspect of the invention relates to a prosthetic implant for replacement of hard tissue of human bones and joints, wherein at least a part of the outside of said implant is composed of a biocompatible construct that is made of metal, and having a porosity in the range of 0-95%, wherein at least a part of the exterior of the construct that is used to attach the implant to bone or joint consists of a curved or planar surface (S) carrying a plurality of protruding parts having a tapered shape and having a sharp top end and each being characterized by a height (H) of 50-1000 μm and a maximum diameter (D_max) of 20-1000 μm, and optionally a plurality of holes, each of said holes having a depth of at least 10 μm and a diameter of at least 10 μm, said protruding parts further meeting the following condition: - V_top < 10,000 μm³; wherein: ■ the height (H) of the protruding part is defined as the minimum distance between the highest point of the top of the protruding part and the intersection between planar or curved surface of the construct and said protruding part;

^■ D_max represents the maximum enveloping diameter of the cross-section of the protruding part that coincides with the planar or curved surface (S);

^■ Vtop represents the volume of the top section of the protruding part, said top section being defined as the section of the protruding part that is located above the imaginary surface that runs parallel to the planar or curved surface (S) 5 μm below the top of the protruding part; and wherein and wherein the planar or curved surface (S) carries at least 50 of the aforementioned protruding parts per cm .

Figure 1 shows a first embodiment of an implant according to the invention in which an array of sharp three-dimensional pyramidal-shaped or saw-tooth like teeth 10 are provided onto a solid metal surface S. The height H of the teeth from the surface S is indicated. Figure 2 shows a second embodiment of an implant according to the invention in which an array of sharp three-dimensional pyramidal-shaped or saw-tooth like teeth 10 are provided onto a surface S which is formed by the upper part of a porous layer 11 such as for instance a porous coating provided onto a solid metal base 12. The height H of the teeth from the porous surface S is indicated. In the drawing, the height H of the teeth 10 is indicated larger, relative to the thickness of the layer S, but may in reality be smaller than the pores in the layer 11.

Figure 10 depicts in an exemplary fashion how the features H, D_max, V_top, Vprotrusion, are determined for a non-porous construct comprising a surface 2 that carries a plurality of protruding parts 3. The protruding parts 3 are sawtooth shaped, each sawtooth having a steep inclined side surface 5, a non-steep inclined side surface 4 and a top 6.

Unless indicated otherwise, the terms "protruding part" and "protrusion" are deemed to be synonyms and used interchangeably.

As explained herein before, the protruding parts of the construct comprise a sharp top end. Thus, these protrusions are intended to be driven into the solid part of bone or joint to provide enhanced fixation. In order to provide sufficient 'sharpness', the volume of the top end of the protruding part V_top as defined herein before preferably does not exceed 4000 μm², even more preferably it does not exceed 2000 μm², most preferably it does not exceed 1000 μm².

The plurality of protruding parts of the present implant advantageously has dimensions that fall within the meso-scale range as defined herein before. Accordingly, in a preferred embodiment, each of the protruding parts is characterized by a height (H) of 20-500 μm and a D_max of 20-500 μm. Even more preferably, the height (H) of the protruding parts exceeds 30 μm, most preferably said height (H) exceeds 40 μm.

The protruding parts of the present implant can take any shape or form. Preferably, however, the protruding parts are triangle-shaped, tetrahedron-shaped or pyramidal-shaped. Even more preferably, the protruding parts are triangle-shape or tetrahedron shaped. Most preferably, the protruding parts are triangle shaped.

Preferably, the protruding parts have an at least slightly elongated form as evidenced by H/D_max > 1.0. Even more preferably, the protruding parts meet the requirements H/D_max > 3.0. In case the protruding parts are triangle-shaped, tetrahedron-shaped or pyramidal-shaped it is preferred that at least one of the sloped faces or sloped sides of these protruding parts makes an angle of 60-120 degrees, preferably of 70-110 degrees, most preferably of 75-105 degrees with the curved or planar surface of the construct. In order to minimize micro-motion of the present implant, it is advisable to ensure that the protruding parts of the implant are harder than the parts of the bone substrate that they are fixed onto. Thus, the so called 'plough' friction and 'wedge' friction effects may be utilized to achieve firm fixation. A simple example of plough friction is observed when a sharp tip is used to produce a scratch in a surface. The plough friction corresponds to the force required to break bonds and push atoms out of the path of the advancing tip. The local pressure required to produce a rearrangement of internal bonds is called the hardness.

The plough friction effect becomes manifest in a fixed implant when protrusions are in direct contact with the interior wall of bone pores. If the implant is moved in a direction that has an exponent that is perpendicular to the bone wall, the bone mass will resist such movement. In other words in order to realize such movement, the protrusion must 'plough' into the bone mass. As regards the present implant, the plough friction effect can be increased by e.g. pushing or hammering the implant into the bone substrate as is common practice in arthroplasty surgery. It will readily be understood that in order to gain maximum advantage of the plough friction effect it is essential that the dimensions of protruding parts are such that they are capable of entering the pores of the bone substrate. Also, it is advantageous for such protrusions to have a sharp side edge, as opposed to a blunt side facing the bone wall. Thus, additional fixation may be achieved as the protrusion can 'cut' into the bone mass when the construct is attached to bone or joint, thereby providing additional contact surface, i.e. friction.

Wedge friction is similar to plough friction, except that wedge friction exerts its effect in all planar ends of bone struts along the of a bone-implant interface. In order to create wedge friction, the tip of a protruding part must be essentially fully surrounded by bone mass. This may be achieved, for instance, by pressing or hammering the protrusions into such bone mass.

The exterior of he present construct consists of a curved or planar surface that carries a plurality of protruding parts and optionally a plurality of holes. The protrusions provide (initial) fixation, whereas holes in the porous coating and the empty space between those protrusions can provide the porosity that is needed for bone ingrowth. According to a particularly preferred embodiment, the biocompatible construct is a porous construct, notably a porous construct that is designed to accommodate bone ingrowth. The porosity of the porous coating can vary within wide ranges, depending on the intended application. Preferably, the porous coating has a porosity in the range of 30-95%.

The footprint area of the protrusions advantageously should occupy less than 30 % of the surface area of the curved or planar surface. If too many protruding parts are employed, it will be difficult to ensure that a significant number of protrusion will enter the bone pores (ploughs) and the solid bone (wedges).

According to a particularly preferred embodiment, the protruding parts of the present implant have the shape of a sawtooth. Here the term 'sawtooth' is used to refer to triangularly side surfaced protrusions whose two inclined sides that together with the curved or planar surface define the triangular shape, have clearly different slopes.

Typically, the steep inclined side makes an angle with the curved or planar surface of 60-120° , preferably of 70-110° and most preferably of 75-105°. It is noted that if the steep inclined side makes an angle of more than 90° this means that both inclined sides rise in the same direction. The non-steep inclined side typically makes an angle with the curved or planar surface of 40-85°, preferably of 50-80° and most preferably of 60- 78°. The difference in slope between the steep inclined side surface and the non-steep inclined surface side advantageously exceeds 5°. Most preferably these angles differ by more than 10°

By employing protruding parts in the shape of a sawtooth the effects of plough and wedge friction may be maximized. Sawtooth shaped protrusion offer the advantage that they are ideally suited for creating plough friction, provided the steep inclined side of the tooth is facing the wall of the bone pore. In addition, it is feasible to design sawtooth shaped protrusion that can be driven into bone and that can thus be used to create substantial wedge friction. In accordance with a particularly preferred embodiment, the present implant comprises a plurality of sawtooth shaped protruding parts that has been arranged in such a way that their steep inclined sides face different directions. By having the steep inclined sides of the sawtooth shaped protruding parts face different directions, it can advantageously be ensured that the level of friction observed at the bone-implant interface is the same in all lateral directions. According to a particularly preferred embodiment, the plurality of sawtooth shaped protruding parts is arranged in such a way that the steep inclined sides of these protruding parts are facing at least 3, preferably at least 4, most preferably at least 6 different directions.

Another advantageous embodiment of the present invention utilizes the "ratchet" concept. The term "ratchet" describes a surface phenomenon that is observed when a surface carries a number of protruding parts that each has anchorage potential and wherein the vectors of said anchorage potential are pointing in the same direction to counteract local micro motion in a predetermined direction.

All types of protruding parts can be used to achieve a ratchet effect, provided their size is within the meso-scale range or the lower end of the macro-scale range. The overall contribution of the ratchet mechanism to static friction against the micro -motion potential is determined by a combination of several factors, including the dimensions of the protruding parts (height, length and width) and the distribution density of the protruding parts along the direction of micro-motion.

The present implant preferably utilizes a 3D ratchet structure. Here the term 3D refers to three-directional rather than three-dimensional. Taking an acetabular cup implant as an example, the possible movement includes translation along the axis direction and two rotations around this axis, clockwise and counterclockwise. Ratchets on the bone-interfacing surface can be arranged in an alternating manner so that they prevent both clockwise and counterclockwise rotation. At the same time, it is also possible to arrange some of the ratchets in a circumferential direction to prevent translation along the axis. In addition, the ratchets may be arranged in such a way as to exert a press-fit effect over the entire circumferential surface as multiple anchorage points.

In accordance with another even advantageous embodiment of the present invention the protruding parts are multi-fold protrusions, i.e. protrusions that carry two or more generations of protrusions, wherein each new generation of protrusions extends from the previous generation of protrusions. In the sawtooth protrusions, for instance, second generation of sawtooth protrusions with smaller dimensions than the first generation can be applied to increase the anchorage effect. This procedure of adding further generations of protrusions can be repeated until the dimension of add-on protrusion reaches the cut-off between waviness and roughness,i.e. 50 micron. The application of further generations of protrusions is illustrated in Figure 6. This figure shows an example of triangular shaped protrusions that carry second generation protrusions that are also of triangular shape. The contribution of the protruding parts to static friction may also be affected by the roughness of these protruding parts. The contribution of the protruding parts to static friction may be enhanced, for instance, by adding micro-scale roughness to said protruding parts, e.g. by adding very small grooves to the surface of the protruding parts. The surface of the present implant that is used to attach the implant to bone or joint advantageously has a surface area of at least 10 cm². In addition, the dimensions of the present implant advantageously exceed 10 mm x 5 mm x 1 mm. Even more preferably, the dimensions of the present implant exceed 30 mm x 20 mm x 3 mm. According to a particularly preferred embodiment, the prosthetic implant of the present invention is composed of two or more thin sheets made of a biocompatible material, each sheet comprising a plurality of through openings and having a thickness of 10-1000 μm, said thin sheets exhibiting a porosity of 20-99%, preferably of 50-95%. The porosity of the thin sheets is determined by the percentage of the sheet surface that has been perforated. Advantageously, the structure of the aforementioned thin sheets, at a scale of

200-2000 μm, resembles the core meshwork of natural hard tissue, especially cancellous bone. According to an even more preferred embodiment, also the three- dimensional structure of the porous implant shares the 3D core meshwork of natural hard tissue, notably that of human cancellous bone. By employing an implant with a porous structure that is similar to that of the hard tissue substrate onto which it is fixated, the coefficient of friction, and consequently resistance to micro-motion, may be maximized.

According to a particularly preferred embodiment the pores within the present porous implant also contain protruding parts. These protruding parts may suitably be introduced in a porous implant composed of two or more thin sheets by adding protrusions to the rim of the through openings in said thin sheets. Thus, in a preferred embodiment of the present invention the thin sheets of the prosthetic implant exhibit the following features: • the rims of the through openings carry a plurality of protrusions, said protrusions having a height or depth of 10-1000 μm and a width of 10-1000 μm;

• the average height or depth of the aforementioned protrusions is in the range of 20-500 μm; and • the average distance between the centers of adjacent protrusions on the rims is in the range of 10-2000 μm.

According to a particularly preferred embodiment, the protrusions on the rims of the through openings have the same dimensions, shape etc. as the protruding parts on the exterior surface of the porous construct. According to a particularly preferred embodiment the protrusions of the rim of the through openings have a sawtooth shape so they can function as a ratchet within the bone-ingrowth region of the porous construct.

According to another preferred embodiment, the rims of the through openings carry a plurality of concave indentations, said concave indentations beings located between and being defined by two adjacent protrusions. Concave indentations provide an inner surface area that is particularly suitable for bone ongrowth.

The outline features of the rim of the through openings are advantageously positioned closely together. Accordingly, the average distance between the centers of adjacent outline features on the rims is preferably in the range of 10-1000 μm, more preferably in the range of 20-400 μm. In accordance with yet another preferred embodiment, the average distance between the centers of two adjacent outline features is less than 5 times the average width of said adjacent outline features. The average width of the outline features is advantageously within the range of 20-500 μm.

The through openings in the thin sheets of the present implant preferably are relatively large. Typically, through openings with a surface area of at least 0.04 mm , represent at least 60%, preferably at least 80% of the perforated surface area of the thin sheets. The average surface area of the through openings preferably is in the range of 0.03-3 mm².

The through openings in the thin sheets of biocompatible material typically contain on average at least 2 surface features per 3 mm of rim. Preferably, said through openings contain on average at least 1 surface feature per mm of rim, most preferably at least 3 surface features per mm of rim. Although the design of the thin sheets and the porous implant may be based on a natural hard tissue, the structure of the thin sheet or the three-dimensional structure of the implant do not necessarily represent an exact copy of the natural hard tissue. As it is virtually impossible to reproduce the natural hard tissue structure at the micro -scale (microstructure) and meso-scale level (mesostructure), the present invention provides a porous implant comprising thin sheets with through openings that, on a meso-scale, have an engineered surface topography with the expectation of better matching for elastic modulus, enhanced surface roughness and increased specific surface area (SSA).

The aforementioned embodiment of the present invention provides a biomimetic copy of a natural hard issue. In order for such a biomimetic copy to perform well when implanted in natural hard tissue, such a copy should have a structural geometry, elastic modulus etc. that is similar to that of the surrounding hard tissue. For instance, there should be no disturbance of the stress lines that pass through the part of hard tissue that is replaced by the present prosthesis. In other words, the prosthesis should form a structural and biomechanical continuum with the surrounding hard tissue. It is particularly important to ensure that the porous implant has an elastic modulus that is similar to that of the surrounding natural hard tissue to prevent the so- called stress-shielding effect.

Thus, in a preferred embodiment, the elastic modulus of the porous implant is less than 50 GPa. Even more preferably, the elastic modulus of the porous implant is within the range of 1 - 20 GPa. Most preferably, said elastic modulus is within the range of 2-8 GPa.

The overall elastic modulus of a porous structure is determined by its specific density of struts (porosity) and cross-sectional area of each strut, which is further determined by the strut width (the breadth of the strut in a 2D image, X-Y plane) and the laminate thickness (Z direction).

The present invention enables the manufacture of porous implants with a predefined elastic modulus by ensuring that the struts within the thin sheets of said implants have a predefined width. Typically, the struts within the thin sheets of the present porous implant have a width of at least 10 μm, preferably of at least 20 μm.

According to another preferred embodiment the ratio of the width of the struts and the thickness of the thin sheet of biocompatible material is at least 0.2. The thin sheets of the porous implant may be composed of any biocompatible materials that provide sufficient strength to the implant. Preferably, the thin sheets are composed of a biocompatible material selected from the group consisting of metal, ceramic, polymer and composites of one or more of these materials. Metals that can be used in accordance with the present invention include any metals or alloys that can be rolled into foil (e.g. titanium, cobalt-chrome, tantalum, stainless steel, magnesium, or any other ductile metal), plated into a foil shape through electro forming or that can be produced in the form of a foil by any other means.

According to a particularly preferred embodiment, the thins sheets comprise at least 60 wt.%, preferably at least 80 wt.% of one or more metals selected from the group consisting of titanium, cobalt, chrome, tantalum, stainless steel, magnesium, nickel and alloys thereof. According to one especially preferred embodiment, the thin sheets comprise at least 80 wt.% of titanium. Titanium sheets offer the advantage that they can be combined into a porous laminate component of exceptional integrity by simply stacking the sheets and heating them to a sufficiently high temperature in a vacuum furnace.

According to another preferred embodiment, the thin sheets comprise at least 60 wt.%, preferably at least 80 wt.% of a shape-memory alloy. An advantage of using a shape memory alloy is that the shape memory alloy may be deformed into a deployable shape, placed inside a prepared cavity within the body and then allowed to return to the initial, desired shape for the implant. Examples of shape-memory alloys include TiNi. Biocompatible polymer materials that can suitably be applied in the thin sheets of the present invention include: nylon, polycarbonate, polymethylmethacrylate, polyethylene, polyurethane, polyaryl etherketone, polyetheretherketone, polylactide, polyglycolide polylactide-co-glycolide and synthetic or natural collagen etc., which may be shaped into a film by blow molding, dip coating, solvent casting, spin coating, extrusion, calendaring, injection molding, compression molding or any other suitable process. Examples of bioresorbable thermoplastics applicable to the manufacturing process described herein include, but are not limited to, poly (DL-lactide) (DLPLA), poly (L-lactide) (LPLA), poly (glycolide) (PGA), poly(g-caprolactone) (PCL), poly (dioxanone) (PDO), poly (glyconate), poly (hydroxybutyrate) (PHB), poly (hydroxyvalerate (PHV), poly (orthoesters), poly (carboxylates), poly (propylene fumarate), poly (phosphates), poly (carbonates), poly (anhydrides), poly (iminocarbonates), poly (phosphazenes), and the like, as well as copolymers or blends thereof, and combinations thereof.

Examples of non-bioresorbable thermoplastics applicable to the manufacturing process described herein include, but are not limited to, polyethylenes, such as high density polyethylene (HDPE), ultra high molecular weight polyethylene (UHMWPE), and low density polyethylene (LDPE), as well as polybutylene, polystyrene, polyurethane, polypropylene, polyaryletherketone, polyacrylates, polymethacrylates, such as polymethylmethacrylate (PMMA), and polymerized monomers such as tri (ethylene glycol) dimethacrylate (TEG-DMA), bisphenol a hydroxypropyl methacrylate (bis-GMA), and other monomers listed herein below, and the like, as well as copolymers or blends thereof and combinations thereof.

Ceramic materials are suitably selected from: alumina, partially stabilized zirconia, hydroxyapatite (HA) -including HA doped with one or more of the following: Si, Mg, carbonate, and the like, calcium phosphates and the like, etc., that may be shaped into a film by tape casting, doctor blade process, robocasting, jiggering or any other process. Thus, any ceramic may be processed by methods of the present invention.

Ceramic or metal implants may be produced with the help of a polymer precursor. In an embodiment of the present invention, ceramics or metal powder materials according to the present invention may be produced using a polymer precursor and subsequent slurry infiltration of the precursor. Conventional slurry infiltration may be done, but it is generally done one layer at a time. Methods of the present invention allow multi-layer infiltration and more uniform distribution of ceramic in a layer and throughout the thickness of the material. This eliminates the problem of suspect porosity or poorly fused material below the surface of porous materials.

A porous ceramic layer may also be produced using a polymer or metal precursor. The precursor may be a "negative image" of the desired material that may be infiltrated with ceramic slurry in a doctor blade process, or, in an alternative embodiment, it may be a "positive image" of the desired morphology and infiltrated by dipping it into an inviscid slurry of water and suspended ceramic or metallic powders. The layers may then be stacked, compressed and fired to fuse particles and layers, resulting in a material with controlled microstructure (morphology and porosity). These approaches ensure that a ceramic material may be produced with uniform microstructure and porosity throughout a bulk shape, if desired. Further, these approaches allow designed variations in the microstructure and porosity at any location within a volume. One method of use for the present invention is termed pressurized tape infiltration, which comprises an adaptation of conventional tape casting where a porous "negative" polymer tape is infiltrated with a ceramic slurry. The infiltrated tapes may then be cut, stacked and/or pressed and shaped prior to sintering the ceramic. Upon sintering the ceramic, the ceramic phase is densified, the layers are diffusion bonded, and the polymer tape is pyrolized, leaving a pore network defined by the original polymer tape. Sintering may be pressureless or pressure assisted.

Ceramic layers or sheets may be microtextured by laser ablation, chemical etching, photochemical etching, or ultrasonic machining. The layers may be stacked as desired. This is followed by a firing step, where the adjacent layers are fused to form a material.

The implant of the present invention may be a composite material of metals, plastics and/or ceramics. The implant may be bioactive or passive. Advantageously, the implant contains bioactive components such as growth factors, antibiotics, steroids and the like. The implant of the present invention provides a natural vehicle for introduction of biological materials and growth factors as it provides an excellent topography and density for the integration of bioactive materials. The biologic material may be incorporated directly into the implant, e.g. by employing a bioresorbable polymer that contains or encapsulates growth factors or other medications. In accordance with another preferred embodiment, the implant comprises a bioresorbable polymer, optionally in combination with other biocompatible materials.

The on-growth properties of the present prosthesis may be further improved by coating the implant with particulate material. The implant may suitably be coated with a coating material by chemical vapor deposition, physical vapor deposition, sputtering, plasma or metal spray, using sol-gel techniques, electroplating, mechanical plating or any other plating technique. Thus, the implant may be provided with a coating of diamond, diamond-like carbon, aluminum oxide, other ceramics or cermets, a metal or metal alloy, a polymer, or a nanometer-scale thick coating of biologic material, including animal, vegetable or human tissue. Advantageously, the pores within the porous implant have been coated with particles, whiskers or fibres made of a biocompatible material. Particularly good results are achieved if the coating material is a ceramic material, especially when applied in a porous implant that is made from stacked thin metal sheets. The benefits of the present invention are most apparent in case adjacent thin sheets within the porous implant have different but coordinated structures. Thus, in a preferred embodiment, protrusions in the adjacent layers can have gradient dimension so that after stacking, those protrusions together form a ratchet in the off-plane direction (Z direction normal to each layer). Those designed ratchets form continuous waviness along off-plane direction. The direction of such waviness should take an acute angle to the bone ingrowth direction.

As explained before, the present invention also provides implants comprising two or more materials. For example, a 2 mm pad may be produced by creating 1 mm of a construct from titanium sheets and 1 mm of a construct from sheets of a biocompatible polymer. A boundary film of the polymer may be partially melted into the metal construct, and the polymer construct portion may then be attached to the exposed polymer layer or the metal construct portion.

According to another embodiment of the present invention, a construct may be made in whole or in part from sheets of a piezoelectric material. Suitable piezoelectric materials include quartz, barium titanate, rochelle salt, lead zirconium titanate (PZT), lead niobium oxide, polyvinyl fluoride, etc. A piezoelectric material generates a voltage when subjected to mechanical stress, and generates a mechanical stress when subjected to a voltage. The implant of the convention may comprise a piezoelectric material encapsulated by another material. For example, such a piezoelectric material may be encased by a metal, polymer or ceramic, and thereby be incorporated into the prosthesis of the present invention without having direct tissue contact.

The present invention also provides a prosthesis comprising an implant as described herein before. The present implant can advantageously be applied in orthopedic implants, dental implants, etc. Furthermore, the implants can be used as bone in-growth surfaces, soft tissue scaffolding, etc.

As explained herein before it is an objective of the present invention to improve fixation of implants onto bone substrates by introducing artificial add-on features or protrusions that increase static friction at the bone-implant interface. The protrusions employed to achieve this goal are not normally generated by surface machining techniques currently used in the manufacture of prothetic implants. Instead, the protruding parts of the implant according to the present invention are incorporated by design. Another aspect of the present invention relates to a method of manufacturing a porous construct composed of two or more thin sheets of biocompatible material as defined herein before, said method comprising: preparing two or more thin sheets of biocompatible material, each sheet comprising a plurality of through openings, having a thickness of 10-1000 μm and exhibiting a porosity of 20-99%, wherein the edge of said two or more sheets and/or the rims of said through openings carry a plurality of protrusions having a height of 10-1000 μm and a width of 10-1000 μm; stacking the sheets of biocompatible material to produce a three-dimensional porous construct; and - binding the stacked sheets, e.g. through physical, chemical or metallurgical methods.

According to a particularly preferred embodiment, the thin sheets of biocompatible material are produced by:

- providing a 2D-image of a porous hard tissue structure of bone or joint; - delineating the outlines of the hard tissue in the imaged porous structure as well as the core meshwork within the same hard tissue, said core meshwork having a predefined minimum width; manipulating the delineated outlines to obtain modified contours, said manipulation comprising the addition of contour features to the delineated outlines whilst ensuring that such addition does not create an overlap between the modified contours and the core meshwork; replicating the modified contours in a thin sheet of biocompatible material; and stacking the sheets of biocompatible material, bonding the stacked sheets. It will be understood that the manipulation of the delineated outlines to obtain the modified contours results in the addition of protruding features that upon replication yield the protruding parts described herein before. The aforementioned method is explained step by step in the following paragraphs. Figure 3a is an original micro -CT image of cancellous bone and figure 3b is the processed version after digital clean-up (5x5 mm).

Figures 4a to 4e depict the individual steps of the aforementioned method. Figure 4a is a cleaned-up image of human cancellous bone comprising pores 1 and the bone lattice 2.

Figure 4b shows the same image, except that further details have been added. The median line 3 runs through the arithmetic center of the bone lattice. The boundaries of the core meshwork are also depicted by the borderlines 4a and 4b. The area between the borderlines 4a and 4b defines the core meshwork of the imaged bone lattice.

Because the distance between the borderlines 4a and 4b is constant, also the width of the core meshwork is constant.

Figure 4c shows the same image and also depicts the core meshwork 5 of predetermined width, a weak strut region 6 and a strong strut region 7 in the original bone lattice.

Figure 4d shows the outlines of the openings 8 that were also depicted in Fig. 4a-4c. In the images shown, there is no overlap between the outline of the openings 8 and the core meshwork, i.e. there are no weak spots. Had this been the case then the outline of the openings 8, in as far as it overlapped with the core meshwork, would have been manipulated to coincide with the boundary of the core meshwork. Thus, such a weak spot is removed effectively. Likewise, at this stage also island of bone lattice are manipulated in order to link them up with adjacent core structure.

Figure 4e shows the image obtained after manipulating the outlines of the openings 8 as shown in Figure 2d. The added contour features 9 together with the original outline of openings form the newly defined modified contours of the openings of the manipulated image. In this case the contour features 9 are triangular protrusions and their crests further define concave features and thus provide an excellent on-growth surface. Care was taken during the addition of the contour features not to create an overlap between the modified contours and the core meshwork. The method of the present invention advantageously utilizes a 2D image of cancellous bone. The thin sheets of biocompatible material so obtained are stacked together to replicate the three-dimensional structure of cancellous bone and exhibit excellent in-growth and on-growth properties together with excellent initial fixation property, especially if the rim of the through openings in said thin sheets carries artificially introduced outline features with the dimensions discussed herein before. According to a particularly preferred embodiment, the present method yields a porous prosthetic implant as defined herein before. The present method offers the advantage that it can be used (i) to manufacture a porous construct having an elastic modulus similar to that of the original bone (ii) to alter the surface topography at meso -scale and (iii) to introduce concave and convex feature to the pore surfaces. In a particularly preferred embodiment of the present invention parts of the delineated outlines of the openings that overlap with the delineated core meshwork are manipulated in order to remove inherent weak spots as shown in Figures 4a-4c. In accordance with this embodiment, the delineated outlines of the openings that overlap with the delineated core meshwork are manipulated in such a way that the manipulated outline coincides with the outline of the core meshwork. Therefore, by predefining the width of the core meshwork, replicated thin sheets of biocompatible material are obtained that, when stacked together in a porous construct, yield a component with a desired elastic modulus. Likewise, by manipulating the width of the core meshwork, also the porosity of the thin sheets and 3D-structure constructed thereof, can be controlled very easily. Typically, the delineated outlines of the openings are manipulated in such a way that the struts within the perforated thin sheet of biocompatible material have a width of at least 10 μm, preferably of at least 20 μm.

In case the 2D image of natural cancellous bone shows "islands" of bone lattice, to facilitate certain processing technique like photochemical machining, those "islands" are advantageously connected with core meshwork by simply adding some contour features and/or struts. In accordance with a particularly preferred embodiment, the delineated outlines of the 2D -image are manipulated by introducing a plurality of protrusions having a width in the range of 10-500 μm. According to an even more preferred embodiment, the average distance between the centers of adjacent protrusions is less than 5 times the average width of the protrusions. The present method enables the manufacture of porous constructs having a predefined morphology and density, regardless of the nature of the biocompatible material used. This allows construction of a consistent structural design from a variety of materials to suit the surgeon's preference and the patient's needs. Methods of the present invention allow production of the same shape of construct from polymers, metals, ceramics, biologic materials or composites, or any combination of these materials.

In accordance with the present method, the delineated outlines of the hard tissue in the 2D image are replaced with an artificially engineered outline to alter the topography and the waviness on a meso-scale. This can be realized by introducing certain waveforms like triangle, square, arc (including hemisphere), sine curve or sawtooth. In another particularly preferred embodiment, the vector waveform introduced has direction which is in an acute or obtuse angle to the propagation direction of the wave.

According to another preferred embodiment, protruding parts are created onto the outside surface of the prosthetic implant by moving the outline features contained within a thin sheet outside the plane of said sheet to form a plurality of protruding parts on one side of the thin sheet. By ensuring that this sheet becomes the top or bottom sheet of the stack of thin sheets that makes up the porous construct, a porous construct carrying a plurality of protruding parts on its surface may be created. Naturally, it is also feasible to create such an construct by first stacking the individual thin sheets and then processing the top and/or bottom sheet in the aforementioned manner.

Figure 5 depicts an example of a thin metal sheet that has been processed in order to convert outline features of the rims of the through openings to protruding parts that can be used on the surface of the present prosthetic implant. A variety of techniques may be used to move the outline features of a thin sheet off-plane. Micro- embossing is a particularly suitable technique for this purpose.

The thin sheets of the present invention may suitably be manufactured with the help of several processing techniques, including laser machining, chemical machining or etching, photochemical machining, plasma etching, stamping and electron beam machining. Alternatively, the biocompatible thin sheets may be produced by chemical etching, photochemical machining, photochemical blanking, electroforming, stamping, plasma etching, ultrasonic machining, water jet cutting, electrical discharge machining or electron beam machining of individual layers.

In chemical etching, a sheet of the desired material has a desired pattern printed onto it, known as the resist. The resist-covered material is then placed in an aqueous bath containing chemicals needed for dissolving the target material, but in which the resist is insoluble. Wherever the sheet is coated by the resist, the material is protected, but where it is exposed, the material is dissolved by the chemical bath.

Photochemical etching is similar to chemical etching, except that the resist pattern is achieved by curing or baking the resist preferentially, using light energy. The uncured photoresist is removed by a process called development.

Stamping involves pressworking operations such as shearing and stretch forming that may produce the desired pattern through direct action of a die set.

Electrical discharge machining uses the heating action of an arc in a dielectric fluid between an electrode and the electrically conductive workpiece. The arc melts a small volume of the workpiece. The arc then collapses and the associated microscopic cavitation results in particles to be suspended in the dielectric fluid. The clearance between the electrode and workpiece is carefully controlled, and the sheet profile is produced that matches the electrode shape.

In ultrasonic machining, abrasive particles impact the workpiece as a result of the agitation from an ultrasonic transducer. A resist pattern placed on the workpiece restricts the resulting machining to unprotected regions as in chemical etching and photochemical machining described above.

In plasma etching, the workpiece is placed in an evacuated chamber where a plasma, commonly fluorine gas, is charged and machines the workpiece. As with chemical etching, a resist defines the resulting workpiece shape.

Electro forming involves the production of a resist, followed by electroplating or electroless plating or a combination of these approaches to produce the desired layer. Different from all the etching processes which are essentially "minus" methods, the electroforming is a "plus" method. Water jet cutting uses the abrasive action of a high velocity water jet to remove workpiece material. The water jet is highly focused, and controlled by a robot and computer, allowing control of the machined geometry.

Electron beam machining uses focused beams of electrons to remove material from an electrically conductive material. It is similar to laser machining, except that the energetic beams consist of electrons instead of light.

Adhesive bonding or other suitable bonding means such as friction welding, ultrasonic welding, cold welding, laser welding, resistance welding, arc welding, brazing, glazing, etc. may be used to join the layers or to attach the material to a solid surface.

The present method is particularly suited for manufacturing sheets of biocompatible material with a thickness in the range of 10 μm to 2 mm. Preferably, the thickness of the thin sheets is in the range of 10-1000 μm, most preferably in the range of 50-150 μm. The thin sheets obtained from the present invention are advantageously used in the manufacture of porous constructs by stacking a plurality of the sheets in such a way that the 3D structure of the porous hard tissue structure is replicated. Typically, such constructs comprise at least 2, preferably at least 10 individual sheets of biocompatible material.

According to another embodiment of the present invention, the thin sheets are used to produce pads of material approximately 2-3 millimeters thick. These pads may then be plastically deformed and bonded or joined to implants. According to a particularly preferred embodiment, the thin sheets are used to produce pads from about 0.5 mm to about 5 mm thick.

In the case the biomaterial employed is metal, 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 less than 10^"3 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.

Figure 12 shows a spherical metal object 16 in which a first set of circular grooves 20, 21 is provided, for instance by milling. Transversely to the first set of grooves 20, 21, a second set of grooves 22, 23 is formed as shown in figure 11. The sets of intersecting grooves define the curved base surface S from which protrusions 13, 14 extend. The depth H of the grooves is for instance 1 mm or less. The width W_g of the grooves is for instance 100 μm, and the distance W between two protrusions is 1 mm or less. The radius R of the object 16 is for instance 33 mm. The object 16 may next be formed into an acetabular cup for use in a hip prosthesis. Since the protrusions 13, 14 are ratchet-shaped, rotational motion of the object 16, when used as an acetabular cup and fixed to the hip bone is prevented. The protrusions 13,14 are arranged in such arrays that they prevent rotation of the actetabular cup around mutually perpendicular axes A and B, such that a multiple ratchet function is obtained resisting rotational motion around the two perpendicular axes in each respective rotational direction.

The invention is further illustrated by means of the following examples:

EXAMPLES

Example 1

A sequence of 5 2D micro-CT images of human cancellous bone was produced. Each image represented an area of 5mm x 5mm. The step-size applied between the respective 2D-images was 0.1 mm.

The original 2D images were cleaned-up digitally to remove noise and micro- scale features. Then artificial designed protrusions were added to the exterior bone- interfacing surfaces. The dimension of all the protrusions were controlled within the meso-scale range, in this example, the maximum height is 470 μm and the maximum (nominal) diameter is 340 μm. Such design meets the requirement for orthopaedic implant that the maximum gap between implant and accommodating bone bed is 500 μm.

To realize a ratchet friction effect, second generation protrusions were added to the first generation protrusions. Therefore, the vector waviness was illustrated in the second generation of protrusions.

The digital stack revealing the anti-micro motion bone-interfacing surface is shown in Fig.6.

Example 2

Example 1 is repeated. The main difference is that in this example both the bone-ingrowth region and the bone-interfacing surface were processed. Furthermore, due to the special bone on-growth requirement for bone-ingrowth region, concave indentations were introduced to promote bone on-growth. The manipulation attempts include: (1) variation of the protrusion waveform: sawtooth, triangle and sine curve; (2) variation of waveform vector direction: inward or outward pore center; (3) the angle of the waveform vector to the internal pore surface: acute or right angle; (4) dimension of the protrusion or indentation: for instance the height was set as 50 μm and 30 μm; (5) the wavelength (density of protrusion). The effects of such manipulation are illustrated in Fig. 7a-7h.

The processed image depicted in Figure 7d was replicated in a titanium sheet (5 mm x 5 mm) having a thickness of 0.1 mm using the following methodology. A photomask was prepared on the basis of the aforementioned processed image. A titanium sheet was cleaned and coated on both sides with photoresist. The titanium sheet was put into the photomask and exposed to UV light The exposed titanium sheet was developed to remove non-cured photoresist - The titanium sheet was subsequently subjected to etching to generate pores; The remaining photoresist was removed and the titanium sheets were cleaned

Figure 8 depicts perforated titanium sheet equipped with contour protrusions in both bone-ingrowth region and on bone-interfacing surface.

Subsequently, the titanium sheets so obtained were stacked in the same order in which the 2D micro -CT images had been obtained. The titanium sheets were subsequently diffusion bonded by heating the stacked sheets in a vacuum oven (10^~5 millibar) to a temperature of about 1000 °C, for 1 hour, under an atmosphere of helium or argon.

The porous lamination implant so obtained had a porous morphology that, on a macro-scale, closely resembled that of the original cancellous bone. At a meso-scale level, however, the natural fractal characteristic of the mineral phase of the cancellous bone was replaced by an artificial waviness in the form of added protrusions.

Fig. 9a shows a three-dimensional digital stack illustrating the bone-ingrowth region equipped with vector waviness. In case the waveform vector has an acute angle with respect to the internal planar surface of pores, these waveforms constitute ratchet functioning in preventing dislodging of in-grown bone tissue. Such ratchet can be formed by coordinating the waveform in the same pore while in the same sheet, and the ratchet formed in such way can be termed as in-plane ratchet. It is also possible to form ratchets by coordinating the waveform (protrusion) in the adjacent sheets with gradient dimension change, the ratchet formed this way can be termed as off-plane or spatial ratchet, as exemplified in Fig.9b.

Example 3 Two types of porous titanium lamination components were prepared in exactly the same way as described in Example 2, the only difference being that no artificial triangular protrusions were introduced during digital processing to the component that was used as a reference. Next, a comparison experiment was performed to measure the coefficients of friction of both types of lamination components.

The measurement of the coefficient of friction was performed as follows: An inclined plane apparatus based on ASTM Specification D4518-91 was used to determine the static coefficient of friction. The apparatus consists of a fixed horizontal plane and a hinged inclined plane for the fixation of cancellous bone. This cancellous bone serves as the substrate and the porous lamination component serves as the slider. The measurement consists of the following steps: (1) increase the angle of tilt, α, of the inclined plane until the lamination component begins to slide down the cancellous bone; (2) calculate the tangent of the angle of the tilt, tan α, this is the coefficient of static friction.

Three types of substrates were tested: (1) wood (reference, due to the fact that wood is porous microscopically); (2) cancellous bone (dry); (3) cancellous bone (wet). It was found that in all three types of substrates that the porous lamination components with meso-scale protrusions had a significantly higher coefficient of friction than the reference component. Both in the case of dry bone and wet bone the coefficient of friction of the lamination component with added outline features was almost twice as high as that of the reference lamination component.

Although the reference sample had no meso-scale artificial contour features, its surface did exhibit micro-scale roughness due to the etching process. The same etching process was applied to both the sample group with protrusions and the reference group. Therefore, the differences observed can only be caused by the introduction of meso- scale protrusions. The experimental results clearly indicate that meso-scale protrusions significantly improve the frictional behaviour.

Example 4

Two identical saw blades were used to prepare a 'sledge', each saw blade forming a slider with exposed sawteeth. The saw blades had a length of 12 cm, a thickness of 380 μm and an asperity density of 1.25 mm^"1. The individual sawteeth had a height of 400 μm and a width of 800 μm. The total weight of the sledge was approximately 50 grams.

Cancellous bone from pig was prepared to provide a flat horizontal surface onto which the aforementioned sledge was placed. Next, a little hammer was used to carefully thump the saw blades. In order to test fixation of the sledge to the cancellous bone, the bone was slowly turned. Unexpectedly, it was found that even if the bone was fully turned, the sledge remained attached to the bone. Clearly, this example demonstrates that meso-scale protruding parts can make a huge contribution to fixation, especially if it is ensured that these surface features penetrate into the solid bone of the substrate.

Claims

1. A prosthetic implant for replacement of hard tissue of human bones and joints, wherein at least a part of the outside of said implant is composed of a biocompatible construct that is made of metal and having a porosity in the range of 0-95%, wherein at least a part of the exterior of the construct that is used to attach the implant to bone or joint consists of a curved or planar surface (S) carrying a plurality of protruding parts having a tapered shape and having a sharp top end and each being characterized by a height (H) of 50-1000 μm and a maximum diameter (D_max) of 20-1000 μm, and optionally a plurality of holes, each of said holes having a depth of at least 10 μm and a diameter of at least 10 μm, said protruding parts further meeting the following condition: - V_top < 10,000 μm³; wherein: ■ the height (H) of the protruding part is defined as the minimum distance between the highest point of the top of the protruding part and the intersection between planar or curved surface of the construct and said protruding part;

^■ Dmax represents the maximum enveloping diameter of the cross-section of the protruding part that coincides with the planar or curved surface (S);

^■ Vtop represents the volume of the top section of the protruding part, said top section being defined as the section of the protruding part that is located above the imaginary surface that runs parallel to the planar or curved surface (S) 5 μm below the top of the protruding part; and wherein the planar or curved surface (S) carries at least 50 of the aforementioned protruding parts per cm².

2. Prosthetic implant according to claim 1 wherein H/D_max > 0.5

3. Prosthetic implant wherein said protruding parts are triangle-shaped, tetrahedron- shaped or pyramidal-shaped.

4. Prosthetic implant according to claim 1,2 or 3, wherein the curved or planar surface (S) carries a number protruding parts that provide a series of ratchet anchoring potentials in mutually different directions.

5. Prosthetic implant according to any of claims 1 to 4, wherein the plurality of protruding parts meets the requirement: H/D_max > 1.0.

6. Prosthetic implant according to any one of the preceding claims, wherein at least one of the sloped faces or sloped sides of the protruding parts makes an angle of 60-120 degrees with the curved or planar surface (S) of the construct, excluding all the side faces making an angle of 90 degrees with the planar or curved surface (S).

7. Prosthetic implant according to any one of the preceding claims, wherein the surface of the construct that is used to attach the implant to bone or joint has a surface area of at least 10 cm².

8. Prosthetic implant according to any one of the preceding claims, wherein the construct has a porosity of 30-95%.

9. Prosthetic implant according to any one of the preceding claims, wherein the construct is composed of two or more thin sheets made of a biocompatible material, each sheet comprising a plurality of through openings and having a thickness of 10- 1000 μm, said thin sheets exhibiting a porosity of 20-99%.

10. Prosthetic implant according to claim 9, wherein: the rims of the through openings carry a plurality of protrusions having a height of 10-1000 μm and a width of 10-1000 μm; the average height or depth of the aforementioned protrusions is in the range of 20-500 μm; and - the average distance between the centers of adjacent protrusions on the rims is in the range of 10-2000 μm.

11. Prosthetic implant according to any one of claims 1-12, wherein the implant is an acetabular cup and wherein the protruding parts form ratchets on the surface of the cup that is used to attach the cup to the bone, said ratchets preventing clockwise and counter clockwise rotation of the cup around its axis, after implantation.

12. Prosthetic implant according to claim 11, wherein the ratchets also prevent translation along the axis of the acetabular cup.

13. A method of manufacturing a construct as defined in claim 9 or 10, said method comprising: preparing two or more thin sheets of biocompatible material, each sheet comprising a plurality of through openings, having a thickness of 10-1000 μm and exhibiting a porosity of 20-99%, wherein the edge of said two or more sheets and/or the rims of said through openings carry a plurality of protrusions having a height of 10-1000 μm and a width of 10-1000 μm; stacking the sheets of biocompatible material to produce a three- dimensional construct; and binding the stacked sheets.

14. A method of providing a prosthetic implant comprising a metal having a curved or planar surface (S) carrying a plurality of protruding parts (13,14) having a tapered shape and having a sharp top (18,19) end and each being characterized by a height (H) of 50-1000 μm and a maximum enveloping diameter (D_max) of 20-1000 μm, comprising the step of providing a first number of parallel grooves (20,21) in the material in a first direction, extending from the top (18,19) of the protrusions to the surface (S) and a second number of parallel grooves (22,23)extending transversely to the first set from the top (18,19) of the protrusion to the surface (15) to form a regular array of at least 50 protrusions per cm².

15. Method according to claim 14, the grooves being formed by machining a spherical surface along a first sets of parallel circular trajectories and a second set of parallel circular trajectories that are transversely to the trajectories of the first set, where after the spherical surface is separated in two halves at least one of which is formed into an acetabular cup.