WO2009109645A2

WO2009109645A2 - Load-bearing bone implant comprising a thermoplastic elastomer

Info

Publication number: WO2009109645A2
Application number: PCT/EP2009/052643
Authority: WO
Inventors: Darren Donald Obrigkeit; Leo Smit
Original assignee: DSM IP Assets BV
Current assignee: DSM IP Assets BV
Priority date: 2008-03-05
Filing date: 2009-03-05
Publication date: 2009-09-11
Anticipated expiration: 2010-09-05
Also published as: WO2009109645A3

Abstract

Disclosed is a load-bearing bone implant of a type suitable for permanent implantation. The implant is made of a thermoplastic elastomer comprising a hard phase and soft phase, wherein the hard phase comprises a polymer chosen from the group consisting of polyester, polyamide, polystyrene, polyacrylate and polyolefin and the soft phase comprises a polymer chosen from the group consisting of polyether, polyester, polyacrylate, polyolefin and polysiloxane.

Description

LOAD-BEARING BONE IMPLANT COMPRISING A THERMOPLASTIC ELASTOMER

The invention pertains to a load-bearing bone implant suitable for permanent implantation. The invention also pertains to the use of the implant in support of bone growth, such as in bone healing and particularly in joint fusion (arthrodesis). The invention further pertains to bone-growth procedures, such as procedures for bone healing and particularly for arthrodesis.

The term "implant" generally has a broad meaning, referring to any foreign object that is placed in a living human or animal body. Implants can be temporary, such as implants in the form of pharmaceutical dosage forms for the controlled release of drugs, or implants that are bioabsorbable and are therefore used for a temporary function. Implants can be permanent, such as a metal pin to support a broken leg. The term "permanent" will be readily understood as referring to anything that is intended to remain indefinitely in the body. This does not mean that the implant could not be removed, e.g. surgically, or could not accidentally disappear. The invention relates to such implants as are suitable for permanent implantation, hence to biostable implants rather than to implants that are bio-absorbable or biodegradable. The latter types of implant, while recognized as useful during bone growth processes, have a disadvantage caused by their biological instability. A biostable implant will remain as is, i.e. once a biologically acceptable implant is introduced into the body of a living human or animal, it is traceable which material is in fact implanted. In the case of an implant that degrades in the body, and/or is absorbed by the body, it will be generally unpredictable which degradation, conversion or metabolic materials will eventually end up in the body. From a viewpoint of controlling the health of the subject receiving the implant, this is undesirable and represents additional clinical risk. Therefore use of resorbable implants are typically restricted to applications where this added risk is balanced by a significant long-term clinical benefit. Moreover, a permanent implant will also be capable of indefinitely contributing to load-bearing. The term "bone implant" generally indicates that the implant is suitable for use related to bone. This can be in, at or around bone, in lieu of bone, near bone or adjacent to bone, etc. The invention relates to such bone implants as are load- bearing, i.e. adapted to be capable of wholly or partially assuming the load-bearing function of bone, and doing so permanently or temporarily. This should not be confused with implants, many of which exist, that are used to preserve joint mobility. The latter refers particularly to artificial spinal disks and other forms of arthroplasty joint spacers (e.g. hip, knee) as well as implants for extremities. These "spinal implants," and other mobility-preserving implants are not bone implants according to the invention. The term "bone implant" even if used in lieu of bone during a process of bone-healing should not be confused with bone replacements, such as artificial joints. Artificial joints are not bone implants according to the invention.

Illustrative examples of load-bearing bone implants suitable for permanent implantation include a wide variety of implants, e.g. orthopaedic implants such as pins to support healing broken bones in legs, arms, wrists and the like, but also cervical cages that are used in the arthrodesis of cervical vertebrae, or spacers used in between dissected bones to support their rejoining, and many other implants. With reference to the use of these implants in e.g. bone-healing, the implants will be load- bearing at least until the bone has healed and will itself be capable of bearing load again. In many constructions for such implant-supported bone-healing, the implant will remain load-bearing itself as well, e.g. as an integral part of the healed bone. Background references in this respect are Clinical Biomechanics of the Spine by Augustus A. White, Manohar M. Panjabi (1990) and Spine Technology Handbook, Kurtz & Edidin, 2007, p. 210.

Depending on the procedure and construction, the load-bearing nature of the implant may be temporary. When used, e.g., in arthrodesis, two adjacent joints (e.g. vertebrae) are made to grow in and around a cage placed between said joints. In the end, the entire construct of implant (cage) and bone (the fused joints) will be load-bearing.

Typical , conventional materials for load-bearing, permanent, bone implants are regular orthopaedic implant materials (e.g. Co-Cr implant alloys, stainless steel or titanium) or - fiber reinforced - high-tensile strength polymeric materials (e.g. polyetherether ketone - PEEK or ultra high molecular weight polyethylene - UHMWPE).

Load-bearing, permanent bone implants are not without problems, particularly due to the fact that these implants are frequently used in a situation that itself is not stable. Thus, e.g., an implant used as a support in bone healing may have a much more prominent load-bearing function until the bone has healed, than thereafter. At the same time, while the implant permanently stays in or at the healed bone, it may serve to remove normal stress from the healed bone. This so-called stress shielding, to which bone implants made of more conventional materials are prone, may result in osteopenia comparable to situations in which the bone is deprived of its normal stress (e.g. such as a leg not used because of injury will become thinner than the other, fully used leg).

It is an object of the invention to provide a load-bearing bone implant, suitable for permanent implantation, that is capable of assuming an adequate load- bearing function, and yet is capable of reducing or even avoiding the effects of stress shielding.

Another problem relates to endplate stability, particularly to subsidence of spacers, such as cervical and lumbar cages, used in arthrodesis of vertebrae. As described by Bartels et al. in Neurosurgery, Volume 58, Number 3, March 2006, pages 502-508, these cages can sink into the vertebral body. A further problem relates to expulsion and/or migration of the implants.

It is desired to provide a load-bearing bone implant, suitable for permanent implantation, that will reduce the chance of such subsidence, migration or expulsion. Another problem associated with conventional load-bearing bone implants suitable for permanent implantation is that bone growth can be inhibited as a result of the presence of the implant. This is believed to be caused by such factors as wear, resulting in debris, or the nature of the material (e.g. silicone osteolysis in the case of silicone implants). In order to better address the desire to overcome or avoid problems with conventional implant materials, a bone implant is provided, suitable for permanent implantation, comprising a thermoplastic elastomer (TPE) comprising a hard phase and soft phase, wherein the hard phase comprises a polymer chosen from the group consisting of polyester, polyamide, polystyrene, polyacrylate and polyolefin and the soft phase comprises a polymer chosen from the group consisting of polyether, polyester, polyacrylate, polyolefin and polysiloxane.

By selecting this particular type of polymer for use in a bone implant, advantageous use is made of a desirable combination of properties. Particularly, the material selected has the ability to provide stiffness at or below that of the surrounding bone. This produces an implant which will retain its shape over time and allow the surrounding bone to regrow while preventing stress shielding and/or inhibition of bone growth associated with implants which are too stiff. Thus, the selection of an elastomer results in a more natural stress behaviour of the resulting implant-provided bone, i.e. different from a more rigid conventional implant. The elastomer better addresses stress shielding, absorbing stress to much more the same extent as bone does. Yet, the - A -

selected elastomer has sufficient compressive and tensile strength to assume the load- bearing function of bone. For this purpose, more traditionally, the aforementioned polymers such as PEEK or UHMWPE are used. These have a very high tensile strength, but a low Young's modulus (tensile modulus of elasticity). The other regularly used materials (the aforementioned metals), suffer from a similar drawback.

In Table 1 an overview is given of various materials and the foregoing properties.

Table 1

1. Spinal Reconstruction- Lewandrowski et al., lnforma Healthcare, 2007, pg. 396.

2. Data sheet, The polymer Technology Group, 2006

3. PEEK datasheet ex Invibio Ltd. (http://www.hoosierinc.com/pdf/Peek%20Optima%20data%20sheet.pdf)

4. Journal of Biomechanics 34(2) 261-266. The TPE's according to the invention will preferably have a tensile strength of from 10-50 MPa, and more preferably within the above-mentioned range for TPE (28-50 MPa). Also, the TPE's used according to the invention preferably have a Young's modulus of 0.01-3 GPa (with the upper values (2-3 GPa) preferably achieved through the use of hard fillers), and more preferably within the above-mentioned range for TPE (0.14-2.6 GPa). Most preferably, the TPE's used in the invention are selected to as to combine these properties within the preferred ranges.

In addition to the judicious choice of TPE materials, the invention thus also pertains to the use, in a bone implant suitable for permanent implantation, of a material satisfying the foregoing combination of strength and modulus. To the extent that the implant according to the invention comprises the aforementioned TPE, and also other elastomeric and/or polymeric materials, the aforementioned ranges will provide the person skilled in the art with guidance on which materials to use. It is preferred according to the invention that the polymer in the implant is substantially (i.e. more than 50%) a TPE as defined above, and it is more preferred for the polymer of the implant to consist essentially of the TPE.

It is well possible, and often preferred, to modify the TPE by rendering it into a composite, e.g. by including fillers. This particularly refers to hard fillers that can be used to provide the TPE with greater stiffness. These fillers can be used in a wide variety of percentages, and by virtue of the good flow properties of the TPE's according to the invention, this can be at a level of more than 50%, e.g. up to 60%. Hard fillers are known to the skilled person, e.g. mineral fillers.

In view of the medical application of the implants, any ingredients in addition to the TPE will at least be biocompatible, and more preferably of pharmaceutical quality.

The implant can be a porous structure containing additives that promote bone growth, e.g. growth factors such as bone morphogenic protein (BMP), transforming growth factor beta and platelet derived growth factor, osteogenic growth factors such as bone-derived growth factor, activin, insulin-like growth factor, basic fibroblast growth factor and combinations thereof.

The TPE according to the invention particularly exhibits low creep and low compression set. Compression set testing is used to determine the ability of elastomeric materials to maintain elastic properties after dynamic stress or prolonged compressive stress. The test measures the somewhat permanent deformation of the specimen after it has been exposed to compressive stress for a set time period. This test is particularly useful for applications in which elastomers would be in a constant pressure/release state, as will be the case for a bone implant that is load-bearing. The compression set for TPE's is only about 15-20%.

Further advantages of the selected TPE's are e.g. a high resilience to mechanical forces, by virtue of its crystalline (hard block) component. Moreover, the TPE can easily be processed to provide a variety of designs, by for example injection moulding. This is an important advantage for use in implants intended for living beings, as the exact shape and size of an implant will normally be determined on an individual basis. In fact, if desired, by using the TPE according to the invention, the shape of the implant according to the invention can easily be adapted during surgery, e.g. to accommodate the patient's anatomy.

The TPE also enjoys a good crack growth resistance, high wear resistance, high dimensional stability and high resistance to moisture, such that a compliant durable implant can be made. A bone implant may comprise only one part. Alternatively, the implant may consist of two or more parts of which at least one part is made of the TPE according to the invention. As such, because of its superior adhesion properties the TPE can be combined with other elastomeric materials of different stiffness and flexibility and/or hard materials, such as metals and higher modulus polymers. Another advantage of using the TPE according to the invention in a bone implant is that the shape of the load-bearing bone implant according to the invention can easily be adapted during surgery to adapt it to the patient's anatomy.

The bone implant according to the invention comprises a thermoplastic elastomer comprising a hard phase and a soft phase. The hard phase in the TPE comprises a rigid polymer phase with a melting temperature (Tm) or a glass transition temperature (Tg) higher than 35 ⁰C. The soft phase in the TPE comprises a flexible, amorphous polymer phase with a Tg lower than 35 ⁰C, preferably lower than 0 ⁰C. The Tm and Tg were determined on a dry sample. The TPE, used according to the invention, comprises, for example, blends of the above-mentioned hard phase polymers with soft phase polymers and block copolymers. The hard and the soft phase can comprise one polymer type, but can also be composed of a mixture of two or more of the above-mentioned polymeric materials. Preferably, the TPE, used according to the invention, is a block- copolymer. When the TPE is a block-copolymer, the TPE used in the bone implant comprises a thermoplastic elastomer comprising hard blocks and soft blocks, wherein the hard blocks comprise a polymer chosen from the group consisting of polyester, polyamide, polystyrene, polyacrylate and polyolefin and the soft blocks comprise a polymer chosen from the group consisting of polyether, polyester, polyacrylate, polyolefin and polysiloxane.

Examples of TPE block-copolymers according to the invention are block-copolyesterester, block-copolyetherester, block-copolycarbonateester, block- copolysiloxaneester, block-copolyesteramide, block-copolymer containing polybutylene terephthalate (PBT) hard blocks and poly(oxytetramethylene) soft blocks, block- copolymer containing polystyrene hard blocks and ethylene butadiene soft blocks (SEBS), polyurethane comprising polybutylene terephthalate (PBT) hard blocks and polycarbamate soft blocks.

The hard blocks in the thermoplastic elastomer consist of a rigid polymer, as described above, with a Tm or Tg higher than 35 ⁰C. In principle the different polymers as described above can be used as the hard blocks. Here and in the rest of the description a polycarbonate or a polycarbamate is understood to be a polyester.

Also copolymers of esters, amides, styrenes, acrylates and olefins can be used as the hard polymer block as long as the Tm or Tg of the hard polymer block is higher than 35 ⁰C.

Preferably, the hard block of the TPE is a polyester block. It has been found that, with respect to their use in the load-bearing bone implant according to the invention, in particular TPE's with a polyester hard block have many advantages including low creep, low compression set, high dimensional stability and high resistance to moisture.

More preferably, in the TPE comprising a hard polyester block, the hard block consists of repeating units derived from at least one alkylene glycol and at least one aromatic dicarboxylic acid or an ester thereof. The alkylene group generally contains 2-6 carbon atoms, preferably 2-4 carbon atoms. Preferable for use as the alkylene glycol are ethylene glycol, propylene glycol and in particular butylene glycol. Terephthalic acid, 2,6-naphthalenedicarboxylic acid and 4,4'-diphenyldicarboxylic acid are very suitable for use as the aromatic dicarboxylic acid. Combinations of these dicarboxylic acids, and/or other dicarboxylic acids such as isophthalic acid may also be used. Their effect is to influence the crystallisation behaviour, e.g. melting point, of the hard polyester blocks.

Most preferably, the hard block is polybutyleneterephthalate. The soft blocks in the thermoplastic elastomer consist of a flexible polymer, as described above, with a Tg lower than 35 ⁰C. In principle the polymers as described above can be used as the soft blocks. Here and in the rest of the description a polycarbonate is understood to be a polyester.

Also copolymers of ethers, esters, acrylates, olefins and siloxanes can be used as the soft polymer block as long as the Tg of the soft polymer block is lower than 35 ⁰C. Preferably, the soft block comprises a polyester or a polyether; more preferably an aliphatic polyester or polyether. A particular advantage of TPE's comprising polyester, or polyether soft blocks is that aliphatic polyesters, and polyethers feature a high chemical stability. Especially, alkylene carbonates and aliphatic polyesthers are preferred as the soft block, which result in thermoplastic elastomers with particularly low moisture sensitivity and favourable adhesive properties. Preferably, the soft blocks in the TPE are derived from at least one alkylene carbonate and optionally, a polyester made up of repeating units derived from an aliphatic diol and an aliphatic dicarboxylic acid.

The alkylene carbonate can be represented by the formula

O

Il

where

R = H, alkyl or aryl, x = 2 - 20.

Preferably, R = H and x = 6 and the alkylene carbonate is therefore hexamethylene carbonate. The aliphatic diol units are preferably derived from an alkylenediol containing 2 - 20 C atoms, preferably 3 - 15 C atoms, in the chain and an alkylenedicarboxylic acid containing 2 - 20 C atoms, preferably 4 - 15 C atoms. More preferably, the soft block comprises a polycarbonate. Most preferably, the TPE comprises a hard block comprising polybutyleneterephthalate and a soft block comprising polycarbonate. Optionally, this TPE is chain-extended with diisocyanate.

Examples and the preparation of block-copolyester esters are for example described in the Handbook of Thermoplastics, ed. O.OIabishi, Chapter 17, Marcel Dekker Inc., New York 1997, ISBN 0-8247-9797-3, Thermoplastic Elastomers, 2nd Ed., Chapter 8, Carl Hanser Verlag (1996), ISBN 1-56990-205-4, and the Encyclopedia of Polymer Science and Engineering, Vol. 12, pp.75-1 17, and the references contained therein.

In another embodiment of the invention polyethylene oxide (PEO) is used as the soft block, which has a good biocompatibility and was found to result in osteoconductive (e.g. bone-bonding) surfaces capable of osteointegration. The PEO soft block can, for example, be combined with a PBT hard block. This can also be applied to adjust the implant surface so as to positively affect bone growth, e.g. by incorporating it as a surface layer or film on another polymer (e.g. the unmodified TPE) as a core. In fact, the possibilities of using adjusting chemistry to modify surface properties can be viewed as an additional advantage of the TPE's as used in the invention.

The ratio of the soft and hard blocks in the TPE used in the load- bearing bone implant according to the invention may generally vary within a wide range but is in particular chosen in view of the desired modulus of the TPE. The desired modulus will depend on the structure and size (e.g. thickness) of the implant and the functionality of the TPE in it. Generally a higher soft block content results in higher flexibility and better toughness.

The TPE according to the invention may contain one or more additives such as stabilizers, anti-oxidants, colorants, fillers, binders, fibers, meshes, substances providing radio-opacity, surface active agents, foaming agents, processing aids, plasticizers, biostatic/biocidal agents, and any other known agents which are described in Rubber World Magazine Blue Book, and in Gaether et al., Plastics Additives Handbook, (Hanser 1990). Suitable examples of fillers, e.g. radio-opaque fillers and bone-mineral based fillers, and binders are described in U.S. Patent Number 6,808,585B2 in columns 8-10 and in U.S. Patent Number 7,044,972B2 in column 4, I. 30-43, which are herein incorporated by reference. Typical fillers are selected from the group of calcium-based fillers (such as calcium phosphate, hydroxyapatite, tricalcium phosphate, calcium sulfate, demineralized bone, autologous bone, coralline substances), carbon-based fillers (such as carbon fiber, graphite, pyrolytic carbon, diamond), polyketones (such as polyetheretherketone - PEEK, polyaryletherketone - PAEK, and polyetherketoneketone - PEKK), ceramic-based fillers (such as bioceramics , zirconium dioxide, alumina, silicon nitride, zirconia-toughened alumina), glass fillers (such as glass fibers, Bioglass®, bioactive glass ceramics, e.g. apatite- wollastonite), metallic fillers & fibers (such as titanium and alloys, tantalum, stainless steels, cobalt chrome alloys, gold, silver, platinum), and mixtures thereof. Preferred are calcium-based fillers, ceramic fillers, glass fillers, and other (stiffer and/or biocompatible) polymers: polyaryletherketone (PAEK), polyetherimide (PEI), polyoxymethylene (POM), liquid-crystal polymer (LCP), polymethyl pentene (PMP), polysulfone (PSU), polyether sulfone (PESU or PES), polyethylene terephthalate (PETP), polymethyl methacrylate (PMMA), polyacrylate, Delrin®, polyacetal, polycarbonates, polyamide, PBT (poly butylene terephthalate). Further preferred fillers are additives to make the PTE (or PTE-composite) radio-opaque: barium and iodine containing compounds or compositions, e.g., barium sulfate and barium sulfate for suspension. Suitable commercially available TPE's include Arnitel^® TPE (DSM

Engineering Plastics), in particular Arnitel^® E (polyether ester, PTMEG), Arnitel^® C, (polycarbonate-ester, PHMC) and Arnitel^® P (polyether ester, polyols, polypropylene and polyethylene). Particularly suitable Arnitel^® grades include 55D, EL250, EM400, EM450, EM550, EM630, EL740, PL380, PL381 , PM381 , PL580, PM581 , 3103, 3104, and 3107.

TPE's, in particular thermoplastic block polyesters have been the subject of numerous FDA regulatory approvals. Specifically, Arnitel^® copolyesters have been listed under the Drug Master Files 13260, 13261 , 13263, 13264, 13259, and 13262. Additionally, these compositions have been cleared for use in permanent implants (510(k) K990952, K896946). According to the FDA MAUDE database, adverse events dating back to prior April, 2000 are mild and due to mechanical failure (see catalogue number 8886441433, 447071 , 8886471011 V, and 8886470401 ). The absence of adverse effects due to material confirms the long-term biocompatibility of these compositions. Arnitel^® E grades are in compliance with the code of Federal regulation, issued by the Food and Drug Administration (FDA) 21 CFR 177.2600 (rubber articles for repeated use) in the USA, the so-called FDA approval. Moreover, US Pharmacopoeia approvals were received for the following Arnitel^® grades: EM400, EM450, EM550, EM740, PL580 and 3104 (USP Class Vl), and PL380 and PM381 (USP Class IV). Moreover multiblock poly(aliphatic/aromatic ester) (PED) copolymers as described in M. El Fray and V. Altstadt, Polymer, 44 (2003) pp. 4643-4650 can suitably be used as the TPE according to the invention.

The invention concerns thermoplastic elastomers as described above, for implants in and near bone, especially those which are surrounded by bone over time, and until then may substitute bone. In many of these applications, the bone implant will perform a spacing function and/or will serve to hold existing bone in place and/or maintain alignment of bone, and thus bear load. The foregoing expressly, and preferably, includes the situation where the bones held in place and/or aligned are joints. These include implants for 1.) facial bones used to augment, reconstruct, correct aesthetic defects (e.g. chin, cheeks, jaw, etc.), 2.) dental applications (to the extent applicable to bone), to retain or maintain the shape of the jaw, 3.) spinal fusion implants, including spinal fusion cages, intervertebral bodies, etc. and 4.) general bone void fillers/bone replacements (e.g. vertebral body replacements). Many different designs, shapes, sizes are known for the type of implants to which the invention relates. This includes techniques and implants such as described by the AO Foundation (Arbeitsgemeinschaft fur Osteosynthesefragen), and included in numerous publications and training courses from the AO Foundation. Published sources include the AO Principles of Fracture Management Second Expanded Edition, the AO Spine Manual, etc.

The implants can be made from the TPE material by any known method to shape such TPEs. Known techniques include (co-)injection moulding, (co-)extrusion moulding, blow moulding or injection overmoulding.

The TPE's according to the invention can be applied in multi component molding, for example, two component (2K) molding, either with other

TPE's, hybrid metal or other polymers. Multi component molding makes it possible to produce designs comprising hard and soft parts, or parts with different properties. Arnitel^® grades are particularly suitable because of their superior adhesion to other types of Arnitel^®, other polymers and metal. Good adhesion prevents separation of the implant parts, which may lead to a number of complications including implant migration, blood vessel and/or nerve damage from the migrated implant, etc. Additionally, multi component molding enables a number of innovative design features. For instance, overmoulding softer TPE grades at specific points in an implant: 1.) enable designs with built-in failure points, e.g. at the points where the softer material has been overmoulded. This provides a predictable failure mode for the implant and a predictable point of failure, which, for example may be intentionally provided to allow the implant to fail in a "safe" mode upon exposure to abnormal or excessive forces and/or to absorb the some of the impact of these forces. 2.) enable designs where implants can be provided in a compact form for minimally invasive surgery where the implant is unfolded and/or expanded after or during implantation.

With reference to different possible types of load-bearing bone implants, and the aforementioned different possibilities for combinations of materials, the TPE of the invention can be used as such, or in a modified form, or combined with other materials. This depends on the key properties desired. Thus, e.g., according to the invention a TPE as defined above can be applied in high load-bearing applications, such as long bone trauma. In such an application, however, the key properties are modulus, tension set, tensile creep, crack, tear, and abrasion resistance. Although these properties can be well provided for by the aforementioned TPE's, it is preferred to use the TPE overmould on titanium, stainless steel, or performance plastic. It is preferred to apply the TPE according to the invention in situations where the material on its own leads to full benefits. This is in general load-bearing implant applications such as in facial bone, trauma of extremities, and particularly in arthrodesis of joints in extremities. In these applications it is preferred to use foamed TPE (i.e. a harder grade), or 2K moulded TPE (e.g. on metal, another TPE, or another polymer).

It is most preferred to apply the TPE according to the invention in compressive load-bearing implants. This refers to e.g. cervical spinal fusion, lumbar spinal fusion, and vertebral body replacements. In these applications, the key properties are compression set, compressive creep, and crack resistance, and in this respect the benefits of the TPE's according to the invention can be enjoyed to the greatest extent. A preferred modification of the TPE in these applications is to use TPE comprising a hard filler, so as to further increase stiffness.

The temperature and other processing conditions at which the TPE can best be processed depends on the melting temperature, the viscosity and other rheological properties of the TPE and can easily be determined by the person skilled in the art once said properties are known. The above mentioned Arnitel^® grades have melting temperatures (measured according to ISO 11357-1/-3) between 180 and 221 ⁰C and are preferably processed at temperatures between 200 and 250 ⁰C.

The TPE's according to the invention, in particular Arnitel^® TPE's, can be sterilized by any known means. The TPE's according to the invention can be foamed by any known method resulting in open or closed cell foam. For example, a hard TPE, e.g. harder than Shore 8OA or 9OA, can be used to provide a foamed end product with good hydrolytic stability, wear and lipid resistance while still providing softer properties. Alternatively a similar effect can be accomplished by applying specific designs, in particular open structures, like a spring-like structure.

3-D selective laser sintering, producing open structure implants of various porosity and open or closed cell structure can be used to modify the surface texture and properties, e.g. hydrophilicity. Fused deposition modelling, as described in for example

Biomaterials, 2004 Aug: 25 (18), pp. 4149-4161 , can also be used to produce open structures with varying degrees of void volume and mechanical properties. In addition, these have been demonstrated to be effective in culturing cells and tissues.

Products, for example those produced by 3-D selective laser sintering or fused deposition modelling, can be tailored for e.g. bone in-growth or bone fusion in a joint by adding osteoconductive filler, for example hydroxyapatite.

The TPE's according to the invention can be cut with a fluid jet for customizing the implant shape to the patient's anatomy. Such fluid jets are described in patent US6960182 and are commercially provided by Hydrocision, Inc. (Billerica, MA). The ability to customize an implant with a fluid jet represents a significant advance over the current standard of practice, where grinding tools (e.g. Dremel) are used to abrade the surfaces of implants, which result in damaged implant surfaces, possible introduction of wear particles in the operating room, etc.

The invention further relates to the use of an implant as described previously, in support of bone growth. Bone growth generally refers to any process in which two or more bones, bone fragments, or bone pieces are made to grow together, to rejoin, or to fuse. Examples hereof include: joint fusion, i.e. when two bones grow together (fuse), such as vertebrae in spinal fusion; trauma, i.e. when two bone fragments or pieces grow together (such as the healing or rejoining of broken bones); reconstruction or correction of anatomical defects, i.e. two bone fragments or pieces created during surgery (e.g. by sawing) are joined. According to the invention, TPE spacers are used between these fragments, and they grow back together.

It is particularly preferred according to the invention to use the above- described TPE's as a bone implant in support of bone healing and particularly in joint fusion (arthrodesis). Bone healing refers to, e.g., healing bone fractures, osteotomies, resections, dissections (either intentional, as in cosmetic/reconstructive surgery, or accidental as in trauma). Arthrodesis refers to a surgical procedure, also known as joint fusion. The goal of arthrodesis is to provide pain relief, restore skeletal stability, and improve alignment in people with advanced arthritis. Not all arthritic joints are candidates for joint replacement surgery. Sometimes arthrodesis is the better surgical treatment option for those with arthritis. Arthrodesis is mostly performed on ankles and wrists but it can be performed on other joints. Arthrodesis particularly is a good consideration for ankles, wrists, thumbs, toes, fingers, and vertebrae, particularly the cervical and lumbar vertebrae. The ends of two bones are fused together in arthrodesis with screw fixation and possible bone grafting. The bone implant is used preferably in the form of a cage/spacer/intervertebral body, but other forms are viable as well.

The invention further pertains to bone-growth procedures, such as procedures for bone healing and particularly for arthrodesis. These procedures by themselves are known to the skilled person, e.g. with reference to the aforementioned publications from the AO foundation.

In a further aspect, the invention relates to the use of a thermoplastic elastomer in a load-bearing bone implant, suitable for permanent implantation, wherein the thermoplastic elastomer comprises a hard phase and soft phase, wherein the hard phase comprises a polymer chosen from the group consisting of polyester, polyamide, polystyrene, polyacrylate and polyolefin and the soft phase comprises a polymer chosen from the group consisting of polyether, polyester, polyacrylate, polyolefin and polysiloxane. The thermoplastic elastomer can be in any of the embodiments described above with reference to implants.

The thermoplastic elastomers used in the present invention can be manufactured in known manner, using regular polymeric synthesis methods.

It is to be understood that the invention is not limited to the embodiments as described hereinbefore. It is also to be understood that in the claims the word "comprising" does not exclude other elements or steps. Where an indefinite or definite article is used when referring to a singular noun e.g. "a" or "an", "the", this includes a plural of that noun unless something else is specifically stated.

The invention will be illustrated with reference to the following, non- limiting Examples and Figures. EXAMPLES

Materials • Arnitel^® EL740 (hard block polybutylene terepthalate (PBT), soft-block: polytetramethyleneoxide (PTMO), modulus 1 100 MPa) from DSM N.V.

• Arnitel^® CM740 (hard block: polybutylene terepthalate (PBT), soft-block: polyhexamethylenecarbonate, modulus 635 MPa) from DSM N.V.

• Arnitel^® EM400 (hard block; polybutylene terepthalate (PBT), soft-block; polytetramethyleneoxide (PTMO), modulus 50 MPa) from DSM N.V.

• Arnitel^® EL250 (hard block polybutylene terepthalate (PBT), soft-block: polytetramethyleneoxide (PTMO), modulus 25 MPa) from DSM N.V. PBT: PBT T06-200 , modulus 2700 MPa from DSM N.V.

• PEEK in Example 3: Ketron ® PEEK-1000, modulus 4000 MPa from Eriks • Elastollan^® 119OA TPU; a polyether-urethane from BASF A.G.

Example I

Arnitel^® EL740 was used to produce a lumbar cage. Force requirements were compared to ISO draft standard ISO/DIS 18192-1 ; which includes peak axial loads of 2000N. The following table 2 summarizes strains and stress on the material given a variety of cage cross-sectional areas. These areas were also compared to the size of the average human endplate (1414 mm² - source: Journal of Biomechanics 36 (2003) 1875-1881 ).

Table 2

According to the Journal of Biomechanics reference, the measured failure stress of human vertebral bone is between 6.3-7.2 MPa. The implant made from Arnitel^® EL740 was thus more than capable of handling these load levels. Furthermore, the strain levels were well within the elastic regime of the material, allowing for good creep performance over time. Further, the TPE used carried the required loads while only taking up a small fraction of total endplate area (thus not interfering with good bone regrowth/fusion).

Example Il

In order to compare the shock-absorbing capacity of a TPE material with a traditional PEEK material, the displacement and energy dissipated under a 2000N load (maximum ISO axial load) was estimated. Energy was estimated as the area under the force/displacement curve and was calculated via numerical integration as show in Table 3 below for Arnitel^® EL740. The implant height was 10mm (disc space), the area was 50 mm².

Table 3

With PEEK of 4 GPa modulus, at 1% final deformation, the energy dissipated was 0.1 J. The TPE used in accordance with the invention was capable of deforming to a much higher extent, and thus absorbed the impact energy rather than merely transmitting it (e.g. to the next vertebra) as PEEK does. In the latter case a higher stress on the next vertebra was produced, which increased the risk of fracturing the endplate.

Example III

The purpose of this example was to compare a spinal cage prepared from different materials.

All cages in the experiments described below will had a rectangular (18x10x6 mm³) open box configuration and wall thickness of 1.5 mm. Cages prepared from three different types of material were tested: a. PEEK (comparative experiment); b. Arnitel^® CM740; hereafter referred to as TPE cage. c. a cage prepared with 2K molding comprising a PBT core of 4 mm thickness with a 1 mm layer of Arnitel^® EL250 at the top and the bottom of the cage; hereafter referred to as 2 K cage.

The following experiments were done:

1. Determination of the mechanical cage properties by static testing Cages must have enough strength to withstand peak loads after implantation. Quasi-static loading tests determined the strength and the stiffness of the bare cage.

Experiments were performed according to ASTM2077-03. Loading speed was 13 mm/min according to the same guideline. In each experiment three cages were tested (n=3).

2. Determination of subsidence into bone under static and dynamic loading regime

Subsidence of the cage into the bone bed was determined according to ASTM 2267, using a polyurethane foam (grade 15, ASTM 1839) as a reproducible bone bed simulator. As incongruence between the implant and the bone bed appeared to be an important parameter for cage loading and subsidence, one foam bed was machined to have a curved surface with a radius of 28mm. The other foam bed remained flat. First, the static strength of an open cage on the foam bed was determined for all three cage types. The foam appeared to fail at a load of some 450N. Subsequently, static loading at 70% of this static strength (i.e.: 300 N) was applied on the two polyurethane blocks and the cage in between for a period of ten minutes. Secondly, a dynamic load (sine wave) of 50-300N was applied at a frequency of 2 Hz for 100.000 cycles (app. 15h) Comparisons were made between empty cages (worst case scenario). The number of samples was three for each type of cage material (n=3).

3. Expulsions experiments

Expulsion testing was performed according to a test described by Goel et al., Summer Bioengineering Conference, Key Biscayne Florida, June 2003. The expulsion test was performed on cages clamped between two flat polyurethane foam blocks (grade 15, ASTM 1839) under a pre-stress of 300N and a constant speed of 0.4 mm/s. The sample number was three for all cage types.

Results

The results of the experiments are given in Table 4.

Table 4

The TPE 2K and PEEK cages were all strong enough to be considered sufficient for in vivo loads in animals as well as humans (equivalent to approximately 10 times body weight).

Surprisingly, both the TPE and the 2K cages showed marked improvements in expulsion/migration.

Additionally, the 2K cage showed further improvements in subsidence. Static and dynamic subsidence experiments showed that the 2K cages performed better in that respect as well: subsidence was more than 20% less as compared to the "hard" PEEK cages. The friction of the 2K cages resulted in the highest expulsion strength.

Finally the 2K cage shows a remarkable behaviour with two ranges of stiffness; first a very low stiffness of both 1.0 kN/mm, followed by a stiffness comparable to the TPC cage (4.3 kN). The stiffness of the TPE and 2K cages were an order of magnitude lower than of the PEEK cages; this should stimulate bone growth within the cage in an in vivo situation.

Example IV

Experiment for comparison of dynamic creep properties

Cylindrical samples having a 13 mm diameter and 6 mm height were mounted between the plates of a MTS 810-11 servo-hydraulic tensile tester. The samples were loaded force controlled by a harmonically time varying compressive force. The cycle frequency of the force signal was 0.25 Hz. The maximum compressive stress during a cycle was 4 MPa whereas the minimum compressive stress was 0.4 MPa. The experiments were carried out in an oven at 37°C. The stress levels that were applied were derived from ASTM 2423-05, and were chosen to be higher by a factor 4.

Results

The sample compression at the maximum and minimum stress during a cycle was monitored as a function of cycle number. The results are summarized in the tables below.

Arnitel^® EM400

By comparing the compressive strain at the minimum stress level it was observed that the Arnitel^® EM400 material clearly showed more creep resistant behavior than the Elastollan^® 1190A material in the tests. For the Arnitel^® EM400 material the compressive strain had increased from 1.4% to 1.9% over 20000 cycles, which is a relative increase of about 35%, whereas for the Elastollan^® 1 190A material the compressive strain had increased from 2.0% to 6.1% corresponding to a relative increase of more than 200%.

Example V

Samples of Arnitel^® EL250, EM400, and EL740 were tested under GLP conditions according to ISO 10993 parts 3, 5, 6, 7, 10, and 11 :

ISO10993-3 Tests for genotoxicity, carcinogenicity, and reproductive toxicity. ISO 10993-5 Tests for in vitro cytotoxicity.

ISO 10993-6 Test for local effects after implantation. ISO 10993-7 Ethylene oxide residuals.

ISO 10993-10 Test for irritation and delayed-type hypersensitivity. ISO 10993-11 Test for systemic toxicity Each of these material grades passed all of the above biocompatibility tests, demonstrating the safety of Arnitel^® TPE as an implant material.

Example Vl

Samples of Arnitel^® types EL250, EM400, and EL740 were tested for the effects of gamma sterilization up to 100 KGray (roughly 4 times a typical sterilization dose). These samples were subsequently mechanically tested to determine the effects on E-modulus, Stress at Break, and Strain at Break. In all instances little or no changes in the material properties were observed.

Claims

1. A load-bearing bone implant, suitable for permanent implantation, comprising a thermoplastic elastomer comprising a hard phase and soft phase, wherein the hard phase comprises a polymer chosen from the group consisting of polyester, polyamide, polystyrene, polyacrylate and polyolefin and the soft phase comprises a polymer chosen from the group consisting of polyether, polyester, polyacrylate, polyolefin and polysiloxane.

2. A load-bearing bone implant according to Claim 1 , wherein the hard phase and the soft phase are present in a block copolymer, wherein the hard blocks are chosen from the group consisting of polyester, polyamide, polystyrene, polyacrylate and polyolefin and the soft blocks are chosen from the group consisting of polyether, polyester, polyacrylate, polyolefin and polysiloxane.

3. A load-bearing bone implant according to Claim 1 or 2, wherein the hard phase is a polyester hard block.

4. A load-bearing bone implant according to Claim 3, wherein the polyester hard block consists of repeating units derived from at least one alkylene glycol and at least one aromatic dicarboxylic acid or an ester thereof.

5. A load-bearing bone implant according to Claim 4, wherein the polyester hard block is polybutyleneterephthalate.

6. A load-bearing bone implant according to any one of Claims 1-5, wherein the soft phase is an aliphatic polyester or polyether.

7. The load-bearing bone implant according to Claim 6, wherein the soft phase comprises polycarbonate.

8. The load-bearing bone implant according to any one of Claims 2-7, wherein the hard phase is polybutyleneterephthalate and the soft phase comprises polycarbonate.

9. A load-bearing bone implant according to any one of the preceding claims, comprising up to 60% by weight of a hard filler, preferably of from 5 to 40% by weight.

10. The use of a load-bearing bone implant according to any one of the preceding claims in support of bone growth, preferably in a method for bone healing, and more preferably in joint fusion (arthrodesis).

1 1. The use of a thermoplastic elastomer comprising a hard phase and soft phase, wherein the hard phase comprises a polymer chosen from the group consisting of polyester, polyamide, polystyrene, polyacrylate and polyolefin and the soft phase comprises a polymer chosen from the group consisting of polyether, polyester, polyacrylate, polyolefin and polysiloxane in a load- bearing bone implant suitable for permanent implantation.

12. The use of a thermoplastic elastomer according to claim 1 1 , in a spinal cage.

13. A load-bearing bone implant according to any one of the claims 1-9, for use in load-bearing bone implantation, preferably for use in compressive load- bearing bone implantation.