CA2111598A1

CA2111598A1 - Hollow endoprotheses with filling which promotes bone growth

Info

Publication number: CA2111598A1
Application number: CA002111598A
Authority: CA
Inventors: Berthold Nies
Original assignee: Berthold Nies; Merck Patent Gesellschaft Mit Beschraenkter Haftung
Current assignee: Merck Patent GmbH
Priority date: 1992-12-18
Filing date: 1993-12-16
Publication date: 1994-06-19
Also published as: MX9308004A; SK144593A3; PL301514A1; TW318792B; ZA939473B; PL174183B1; ATE178773T1; EP0605799A1; DE4242889A1; AU5239793A; DE59309514D1; CZ277893A3; NO934678D0; CZ283725B6; HU9303639D0; KR940013468A; HUT67146A; CN1090746A; ES2132164T3; NO934678L

Abstract

Abstract The invention relates to an endoprosthesis which has at least one hollow structure which can be implanted in a bone bed and is provided with openings, where the hollow structure contains a filling which promotes bone growth and which consists of a material which forms a porous matrix and which contains one or more peptide growth factors. A prosthesis of this type shows improved healing-in behaviour and has a longer useful life.

Description

:. -Merck Patent Gesellschaft mit beschrankter Haftung 6100 D a r m s t a d t ~-Hollow endoprostheses with filling which promotes bone qrowth ~ -The invention relates to a hollow endopro~the~i~
for bone replacement which contains a filling which promotes bone growth.
- Bone implants are required for replacing bone defects, for example to close gap~ after fractures and bone tumour operations, for cysts or as joint prostheses such as, in particular, for hip joint replacement. Bone prostheses, as a rule, are fabricated from metallic materials which are compatible with the body and must correspond in shape and function to the original bones or parts of bone which they are intended to replace. Hip endoprostheses have a stem by which they are inserted into the proximal part of the femur after removal of the articular head and spongiosa. ~ip endoprostheses are, by their ~ature, exposed to high static and dynamic stres-ses. Thus, in the design o~ prosthe~es, attention, besides being directed at anatomically appropriate shaping, must be directed in particular both at a stabi-lity, which complies with requirements, of the prosthe~is as such and at its firm and permanent connection to the femur. Inadequate matching of strength, elasticity and -~ -rigidity of the prosthesis may lead to premature breakage or loosening, disengagement and breaking out of the implantation bed.
On implantation it is important that there is a non-positive connection between prothe~is stem and bone bed in order to achieve adequate primary strength.
Depending on the design of prosthesis, this can take place by positive cementing-in of the pro~thesis or by a cementless implantation technique in which non-positivity must be ensured. There i~ a particular need in the second ca~e for the preconditions for an intimate connection of prosthe~is and bcne by bony integration and healing-in to , ~ ~J~ g~

be provided by an appropriate design of the prosthesis so that the required long-term stability of the prosthesis is ensured.
Recent developments in the design of pro~theses are moving toward~ hollow prostheses (see Z. Orthop. 129, 453 (1991)). In the case of hip prostheses there is an increasing trend away from the previously customary solid design, and the prosthesis stem is being designed as hollow stem with openings. The design of the prosthesis stem as hollow body ha~, besides savings in material and weight, on the one hand the advantage that the local requirements concerning strength, elasticity and tor-sional stiffness can be complied with more fully. On the other hand, the aim is to achieve, by bone growing through the openings and growing into the interior of the stem, a permanent secondary strength.
~ owever, the construction of new endogenou~ bony substance is a lengthy proces~. Without additional artificial assistance by measures which promote bone growth, the growing of trabeculae through the cavitie~ of hollow endoprostheses cannot be achieved in acceptable periods of time. The best possibility to date for stimu-lating growth of bone into the prosthe~is i8 to fill the prosthesis cavities with autologous or homologous spongy bone material. Autologous spongiosa, that is to say material derived from the same individual, is, as a rule, avail~ble in a ~uitable form and quantity only to a limited extent. Where it cannot be obtained directly at -the site of implantation it must be removed via an addi-tional surgical intervention from another ~ite, whichmakes the operation overall more complicated, causes additional pain and requires further healing processes at the site of removal. Analogous statements apply to homologous bone material taken directly from other individuals or from the bone bank. In the ca~e of homologous bone material there are also problems of compatibility owing to immunological reactions, as well as the risk, which cannot be entirely excluded, of infection with v;ruses such as, in particular, hepatitis ,: - :

_ 3 _ ~ 9 8 and HIV viruses. Furthermore, the storage of donated material in bone banks is costly and, in the final analy~is, possible for only a limited time.
In addition, administration of biological materials of this type into the hollow prosthesis i~
possible only immediately before or during the operation.
Corresponding finishing of the prosthesis a long time beforehand, together with storage, is virtually impossible.
It is possible, and also practicable, to charge hollow endoprostheses with body-related materials which are synthetic or partly synthetic in nature and which display an osteoinductive and/or osteoconductive effect.
Appropriate bioactive materials are regarded as being calcium compounds, in particular calcium phosphates such a~ hydroxyapatite and tricalcium phosphate, but al~o calcium carbonate, each of which can preferably be emp-loyed in the form of granule3. Hydroxyapatite which has been obtained from natural bone and is, where appropri-ate, sintered to a ceramic is also ~uitable for thispurpose. However, all materials of this type are far from showing the effect of autologous and homologous bone material in promoting bone growth.
The invention was therefore based on the object of making available for filling hollow endoprostheses a material whose effect in promoting bone growth comes as close as possible to that of endogenous bone material. It ought to be possible for a bone replacement material of this type to be made available in any desired amount and in a form ~uitable for filling hollow prosthese~, and it ought to be po~sible for the prosthe~is to be finished~a long tLme beforehand and be stored without problems when filled. In addition, the material ought to be well defined and of reproducible and standardizable quality.
It has now been found that these requirement~ are met in an outstanding way by a bone replacement material which consists of a material which forms a porous matrix, where the matrix contains one or more peptide growth factors. Suitable materials are de~cribed in an earlier, ~ ~ 4 ~ ~ f~ 8 not previously-publishsd, application of our own, P 4121043.
The invention thus relates to an endoprosthesis which ha~ at least one hollow structure which can be implanted in a bone bed and is provided with openings, where the hollow structure contains a filling which promotes bone growth and which consists of a material which forms a porous matrix and which contains one or more peptide growth factors.
The invention particularly relates to an endoprosthesis of this type in which the filling which promotes bone growth essentially consists of calcium compounds, preferably of sintered calcium phosphate ceramic, which form a porous matrix, and contain~ one or more polypeptides having the biological effect of fibroblast growth factors.
The bone replacement materials which are to be employed according to the invention as fillings which promote bone growth in hollow endoprostheses have the common feature that they contain in a porous matrix one or more peptide growth factors.
Suitable matrix materials which can be present are in principle all kn~wn and conventional implant material~ as lon~ as they represent or have a porou~
matrix to receive growth factor~. Suitable implant materials can be divided into the clas~es of mineral, in particular cer~;c, materials, phy~iologically acceptabls polymeric materials and composite materials composed of two or more materials of the said type. These materials can in their entirety form a porous matrix, for example in the form of porous shaped articles, powders or granules, or only particular portion~ of the material may be present as porous material. The latter possibility can be achieved, for example, in such a way that a composite material contains a porous component.
With regard to materials, the materials preferred ~or the prosthesis filling materials according to the invention are those which are of a mineral and, in particular, ceramic nature.

5 ~ 8 Preferred mineral materials in this connection are those which are intrinsically bioactive. This prin-cipally applies to materials which are based on calcium compounds such as, in particular, calcium carbonate, S calcium phosphates and systems derived from these com-pounds. To be mentioned as preferred from the group of the calcium phosphates are hydroxyapatite, tricalcium phosphate and tetracalcium phosphate. Calcium compounds of this type are regarded, on the basis of their chemical relationship with the mineral phase of natural bone, as bioactive. The principal constituent of the mineral phase of natural bone is hydroxyapatite, a calcium phosphate of molecular formula Ca5(P0~)30H. Hydroxyapatite of synthetic or organic origin, for example from natural bone material, is therefore a commonly used raw material for the production of implant materials for bone replacement.
Hydroxyapatite ceramic essentially cannot be resorbed by the body or is broken down by the body only very slowly and over a long period. The exogenous material remains virtually unchanged over a long period, and integration into the body takes place essentially by knitting with bone which is present and which is newly formed and by growing into the surrounding ti~sue. Tricalcium phosphate can be resorbed in the body under certain circumstances.
Calcium phosphate taken up by resorption by the body i8 available for reconstruction of endogenous bony sub-stance. Tetracalcium phosphate essentially cannot undergo biore~orption.
Porous calcium phosphate ceramics show particularly favourable growing-in behaviour.
Particularly preferred in this connection are materials based on natural bone, which i~ mineralized by various treatments and converted by sintering into a ceramic system, the intention being to retain as far as possible the structure of the bone. A co~mon feature of these treatments is the removal of the organic constituents of the bone and the sub~equent consolidation to a ceramic by sintering at appropriate temperature~. The removal of the organic portions takes place by chemical dis301ving - 6 ~ 9 8 processes or by pyrolytic methods. Detail~ on bone ceramics and particularly favourable methods for produ-cing them can be found, for example, in the patent documents DE 37 27 606, DE 39 03 695, DE 41 00 897 and D~ 40 28 683.
Analogous statements apply to porous materials which are obtained from the inorganic substances, which essentially consist of calcium carbonate, forming the framework of marine life forms such as, in particular, corals. Materials of this type are employed as such, or after a chemical conversion into calcium phosphate and, where appropriate, sintering to a ceramic, as bone replacement materials. Materials of this type are descri-bed, for example, in US Patent 4,861,733.
Because there is an excellent match between bone ceramic materials and the pore system of natural bone, the former demonstrate considerable biological advantages with regard to the growing-in behaviour and the healing in the body. Sintered spongiosa bone ceramic is particu-larly preferred because of its highly porou~, three~
dimensionally open-pore network structure.
Detailed investigations have s~own that exposed ~ineral contact surfaces in implant materials made of calcium phosphate ceramic preferentially stimulate the formation of new mineralized bone matrix, which results in a stronger knitting of the implant. This procesa is also further promoted in the case of porous implants where, because of the greater surface area and owing to the growing-in of new bone tissue, there is an element of a particularly pronounced intermeshing and thus mechani-cally stable knitting. In the case of implant materials composed predominantly of polymeric materials or of bioinert materials, there is, instead of this, formation, initially preferentially in the contact region, of connective tissue, which lead~ to only moderately strong knitting.
The porous matrix materials are preferably in the form of powders or granules but can also be ~haped articles adapted to the geometry of the prosthe6is cavity. Matrix materials which are finely divided expediently have a particle size of 1-5 mm, preferably 2-4 mm. Spherical particles are preferred and allow the prosthesis cavities to be filled more easily and with better compaction.
Suitable and preferred composite materials are those in which at least one component is in the ~orm of a porous matrix to receive growth factors. Expedient materials are those in which a porous mineral matrix is in the form of a powder or granules and forms a composite with a phy~iologically accepta~le polymeric material.
Composite materials of this type are to be found in the relevant specialist literature, for example the patent documents WO 90-01342 and WO 90-01955, which de~cribe Lmplant materials based on calcium phosphate and bone cer~m;c particles, respectively, and on bioabsorbable polymer. ~ypical compo~ite materials of these types consist, for example, of spongiosa ceramic and collagen or lactide or glycolide polymers. Depending on the nature and compo~ition, these materials can be in the form of granules or of more or less plastic masses.
Growth factors which are present in the bone-growth-promoting fillings according to the invention for hollow endoprostheses are known as such in wide diver-sity. These are endogenous peptideæ with, in some cases,a broad spectrum of activity in growth and healing processes. They can be obtained from biological material or by genetic engineering methods. A comprehensive review of these i8 provided, for example, by the monograph "Peptide Growth Factors and their Receptors I" (Editors:
M.B. Sporn and A.B. Roberts) Springer Verlag ~erlin, Heidelberg, New York 1990.
Particularly preferred for use for the purpo~e of the invention are fibroblast growth factors [FGF) which likewise belong to the class of endogenous peptide growth factor~. These were originally detected as substances in the brain and pituitary and i~olated therefrom, and showed a growth-promotion activity on fibrobla~ts. FGFs are known as effective, angioge~ic factor3 which are '~ - 8 _ ~ 98 responsible, inter alia, for neovascularization in wound healing. More details on FGFs, including their modifica-tions, on their isolation and preparation, their struc-ture, their biological activities and their mechanisms, as well as on appropriate medical uses, are to be found in the specialist literature which is now wide-ranging.
A comprehensive presentation of current knowledge about them is to be found in the article "Fibroblast Growth Factors" by A. Baird and P. Bohlen in the abovementioned monograph.
Growth factors which are to be regarded a~
suitable according to the invention are not only the "classical" FGFs such as acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) but also all peptide growth factors which show the biological effect of FGF.
The more restricted group of FGFs includes native FGFs, especially of bovine and human origin, as well as FGFs prepared in a recombinant manner. Human aFGF and bFGF prepared in a recombinant manner are particularly preferred. Details on bovine and human aFGFs and bFGF~
prepared in a recombinant manner are to be found, for example, in the following patent documents: EP 228 449, EP 248 819, EP 259 953, EP 275 204. The wider group of FGFs also includes muteins which differ from aFGF or bFGF
to a certain extent in the number and/or sequence of the amino acids without this being associated with an essen-tial change in the effect. The wider group of FGFs finally al~o embraces related peptide~ with, in some cases, distinctly different amino-acid sequences having the effect of FGF and having activity which enhances the effect of FGF. Literature references which may be mentioned are, for example, the following patent docu-ments: EP 148 922, EP 226 181, EP 281 822, EP 288 307, BP 319 052, FP 326 907 and W0 89-12645.
FGFs for the purpose of the invention furthermore include derivatives of the~e peptides which are obtained with stabilizing and/or activity-enhancing agentæ. These are, in particular, form~ of aFGF and bFGF which are 9 ~ 9 8 stabilized against acid and which contain as stabilizing agents, for example, glycosaminoglycans such as heparin, heparin fragments, heparan sulfate and dermatan sulfate or glucan sulfates such as dextran sulfhate and cyclo-dextrin sulfate. FGF derivatives of this type aredescribed, for example, in EP 251 806, EP 267 015, EP 312 208, EP 345 660, EP 406 856, EP 408 146, WO 89-12464, WO 90-01941 and WO 90-03797.
Particularly preferred for use in the bone-growth-promoting filling~ according to the invention for endoprostheses are the forms of human bFGF which are prepared in a recombinant manner and described in EP 248819.
The growth factors can be present in the fillings according to the invention in a concentration of 1 ng/cm3 - 1 mg/cm3. The choice of the concentration within the said range may depend upon the nature and form and on the activity of the growth factor to be employed in the individual case, as well as on the nature of a porous material provided in the individual case and its bio-activity which i~ inherently present where appropriate.
The FGF concentration is preferably in the range from 1 ~g/cm3 to 100 ~g/cm3.
The production of the filling materials according to the invention by charging the particular porous matrix with peptide growth factors, in particular with polypep-tides having the effect of FGF, is intrinsically straightforward. It is expedient to start from a suitable liquid preparation of the growth factor, for example in the form of a ~uffered aqueous solution, and to allow it to be absorbed completely in the intended dosage into the porous matrix of the bone replacement material. The filling material is then, or after a drying which may be nece~sary, ready for use or can be stored with the precautionary measures which are necessary for such materials for medical use. It is po~sible in this way to charge porous shaped articles, powders and granules, preferably composed of bone ceramic, and porous particu-late components for compo~ite materLals with growth 5 9 8 .

factors.
Charging with combinations of various growth factors which complement one another in their ~pectrum of effects or synergistically influence the activities can also take place analogously. The combination of FGF~ with BMPs (bone morphogenetic proteins) is expedient, for example.
The bone-growth-promoting materials according to the invention for hollow endopro theses can be charged, in addition to the growth factors, also with other active substances which promote bone formation or inhibit bone destruction. Suitable active substances are vitamin3 with appropriate activity, such as those of the D complex, and hormones such as calcitonin.
It may moreover be worthwhile to charge the porous matrix material~, in addition, with other pharma-ceutically active substances in order, in this way, for example, to minimize the risks of infection. Suitable examples are antibiotics such as gentamicin and clinda-mycin, and combinations thereof.
The prostheses intended for filling with the filling materials which promote bone growth are in principle all those which serve to replace or reconstruct bone structures, which are implanted at least partly in originally-present bone structures and which are intended there to enter into a permanent connection with the endogenous bony substance by knitting and growing in. In order to make it possible to fill the endoprostheses according to the invention with the filling materials which promote bone growth, the endoprosthe~es must have at least one hollow structure which can be implanted in a bone bed and is provided with openings and into which the filling material can be pla~ed.
Endoprostheses for replacing a wide variety of bone structures, and which have a hollow structure suitable for filling or can be designed for this purpose, are known per se. Particularly appropriate, and preferred because of the medical need, are hip joint endopros-theses. As a general rulet they have an elo~gate stem which carries the actual articular head, which shaft is implanted into the femur and can be designed as a tubular and/or hollow structure provided with openings. Hollow endoprostheses provided with the bone-growth-promoting filling according to the invention and intended for hip joint replacement are a particularly preferred embodiment of the invention.
Further endoprostheses which can be designed analogously for filling with the filling material accord-ing to the invention, which promotes bone growth, areknee joint prostheses, elbow prosthe~es and prostheses for replacement of vertebrae.
The endoprostheses according to the invention can be finished with the filling which promotes bone growth in a variety of ways and, if necessary, also sequen-tially.
The filling of the prosthesis cavities with filling material in the form of a powder or granules is straightforward. However, in this case it may ~e appropriate to close the openings of the prosthesis cavi-ties with a cover in order to prevent the filling falling out during storage and manipulation during the operation.
Suitable covering materials are thin networks which have a tiled ox woven structure and which are preferably fabricated from bioabsorbable material3 such as collagen, gelatin, chito~an or its derivatives or lactide- and/or glycolide-based polyesters. ~osiery fabrics which are sLmply pulled over the prosthesis are particularly prac-ticable.
It is possible for the same purpose to use solutions of such biopolymers subsequently to bond or impregnate the filling. Such a measure can, where appro~
priate, additionally effect a stabilization or a control of the release of the growth factors contained in the filling and, possibly, other active substances.
Porous matrix shaped articles are expediently adapted in their shaping to the prosthesis cavitie~ in which they are to be inserted.
Composite materials ~uch as, in particular, ~:

: . : ~

- 12 - ~ 98 materials composed of spongiosa ceramic granules and lactide or glycolide polymers can be designed such that they can undergo plastic deformation at room temperature or slightly elevated temperature. Plastic masses of this type can be used for durable filling of hollow endopros-theses by simply being pressed into the corresponding cavities.
Either the prostheses can be filled with matrix material already charged with growth factor, or the charging of the porous matrix is carried out only after the filling of the prosthesis.
In one possible embodiment, the endoprosthesis according to the invention is complete and ready for implantation with the filling containing growth factors.
lS Its advàntages are ~imple, rapid manipulation and a correspondingly short operation ti~e.
In a preferred embodiment, the endoprosthesis according to the invention is in the form of an implanta-tion kit which is ready for use and consists of two or more separate components in which one component is a prosthesis shaped article which contains the porous matrix and another component contains a liquid prepara-tion of the polypeptide. An embodiment of this type i8 particularly expedient in order effectively to counter possible stability problems which might occur on long term storage of endoprostheses according to the invention which have already been finished. Thus, for example, it has been reported in the ~pecialist literature that calcium ions, which, after all, are present in the materials preferred here, may have a destabilizing effect on FGF. The mode of use of endoprosthese~ according to the invention in the form of an implantation kit of this type is to charge the porous matrix of the pro~thesis filling with the solution containing the growth factor in the prescribed manner shortly before or during the surgical intervention for the implantation. It i8 ex~
pedient in this connection to match the volume of the - liquid preparation containing the growth factor as accurately as possible to the uptake capacity of the - 13 _ ~ 9~
porous matrix in order to ensure complete and uniform charging.
Consideration should furthermore be given to separate packaging of prosthesis body, porous filling material and the liquid preparation containing the growth factor and/or other active substances in the form of an implantation kit. In this case too the volume of the prosthesis cavities, the amount and uptake capacity of the filling material and the volume of the liquid component should be matched to one another.
The hollow endoprostheses according to the invention, with a filling which promotes bone growth, have a number of advantages which represent valuable improvements.
It has emerged that the porous filling materials stimulate, es~entially irrespective of the nature of the material, owing to the charging with growth factors, a considerable formation of new mineralized bone matrix after the implantation in the contact region and, depend-ing on whether growth through them is possible on the basis of porosity and/or absorption, al80 in theix interior. This i~ in every case significantly greater than in corresponding uncharged prosthesis filling~. In this case it was possible to observe a pronounced ~yner-gistic effect with porous prosthesis fillings which werecharged with FGF and based on calcium compounds, in particular calcium pho~phate ceramics. Thus, preclinical model tests on pig~ showed that there was complete incorporation into the bone, owing to newly formed, predominantly mineralized, bone matrix growing in and through, twelve weeks after the Lmplantation using bone ceramic prosthesi~ fillings charged with FGF. A com~
parable result was achieved only with a pro~thesis filling with autologous spongiosa whereas, for example, with uncharged bone ceramic it was possible to find knitting, owing to formation of new bone matrix, only in the regions in contact with existing bone. It is a~sumed that there i8 a mutual potentiation of the effect of FGF
in promoting bone growth and the bioactivity of calcium-~ 5 9 8 containing matrix materials such as, in particular, bone ceramics, thus leading to faster setting and incorpora-tion of the prosthesis.
This improved growing-in behaviour results in an improved secondary strength and thus a longer useful life of the implanted prosthesis. The present invention is a considerable advance, especially for prostheses which are intended for the cementless implantation technique.
Since the prosthesis filling which promotes bone growth need not, like autologous spongiosa, be obtained only before or during the implantation, there are no problems with amounts thereof. The surgical intervention is simplified as a whole, made of shorter duration and has fewer complications for and i8 better tolerated by the patient.
Problems which may arise with the uRe of homolo-gous bone material as prosthesis filling, such as infec-tions and immunological reactions, are ruled out by the invention. -The prosthesis filling according to the inven-tion, which promotes bone growth, makes available a well-definable, reproducible material of standardizable quality and controllable biological activity. --Example 1 ~ ~-25 Filled hip joint prosthesis ~ ~-A prefabricated commercially available hip joint - -~
prosthesis made of titanium alloy, and having a tubular hollow stem provided with openings, i8 completely filled with granules (particle size 2-4 mm) of hydroxyapatite/-spongiosa ceramic (prepared as described in DE 40 28 683?. A syringe is used to introduce into the porous filling, to saturation, a buffered solution of human bFGF prepared in a recombinant manner, so that the prosthesis filling is charged with 50 ~g of bFGF/cm3.
The prosthesis i8 freeze-dried under sterile conditions and packaged sterile. It is then ready for implantation.

.~

Example 2 Implantation kit A hip joint prosthesis filled with hydroxyapa-tite/spongiosa ceramic as in Example 1, but not charged with bFGF, is sterilized and packaged sterile.
bFGF solution in citrate buffer (10 mM; pH 5.0) is, after addition of sucrose solution (9~), freeze-dried and dispensed into ampoules. The ampoule content~ and the ampoule volume are adjusted in such a way that the prosthesis filling is subsequently charged with 50 ~g of bFGF/cm3.
Prosthesis packs and bFGF ampoules form pack units as implantation kits.
con~l5i9ni~9L---the o~erating table The bFGF ~olution is reconstituted in citrate buffer (pH 5.0) and subsequently drawn into a ~terile syringe.
After the package has been opened, the bFGF
solution is introduced into the porous prosthesis fil-ling. q'he volume injected is such that the filling is completely saturated with the bFGF solutionO Excess bFGF
solution i~ withdrawn into the syringe after about 1 minute. The amount of solution retained by the prosthe-sis filling approxLmately corresponds to its pore volume.
The charged prosthesi~ can now be implanted.

Claims

1. Endoprosthesis which has at least one hollow structure which can be implanted in a bone bed and is provided with openings, characterized in that the hollow structure contains a filling which promotes bone growth and which consists of a material which forms a porous matrix and which contains one or more peptide growth factors.

2. Endoprosthesis according to Claim 1, charac-terized in that it is a hip joint prosthesis in which the prosthesis stem to be implanted in the femur is designed as a hollow structure which is tubular and/or provided with openings.

3. Endoprosthesis according to Claim 1, charac-terized in that it is a knee joint prosthesis.

4. Endoprosthesis according to Claim 1, charac-terized in that it is an elbow joint prosthesis.

5. Endoprosthesis according to Claim 1, charac-terized in that it is a prosthesis for replacement of vertebrae.

6. Endoprosthesis according to one of Claims 1 to 5, characterized in that the porous matrix essentially consists of calcium compounds.

7. Endoprosthesis according to Claim 6, charac-terized in that the porous matrix essentially consists of calcium phosphate.

8. Endoprosthesis according to Claim 7, charac-terized in that the porous matrix consists of one or more compounds from the group comprising hydroxyapatite, tricalcium phosphate, tetracalcium phosphate.

9. Endoprosthesis according to one of Claims 6 to 8, characterized in that the calcium compounds are obtained from natural bone.

10. Endoprosthesis according to one of Claims 7 to 9, characterized in that the porous matrix is sintered calcium phosphate ceramic.

11. Endoprosthesis according to Claim 9, charac-terized in that the porous matrix consists of sintered spongiosa bone ceramic.

12. Endoprosthesis according to one of Claims 6 to 11, characterized in that the porous matrix is in the form of a powder or granules.

13. Endoprosthesis according to Claim 12, charac-terized in that a porous matrix forms a composite with a physiologically acceptable polymeric organic material.

14. Endoprosthesis according to one of Claims 1 to 13, characterized in that it contains in the porous matrix one or more polypeptides with the biological effect of fibroblast growth factors.

15. Endoprosthesis according to Claim 14, charac-terized in that it contains basic fibroblast growth factor.

16. Endoprosthesis according to Claim 14, charac-terized in that it contains acidic fibroblast growth factor.

17. Endoprosthesis according to Claim 15 or 16, characterized in that it contains fibroblast growth factor prepared in a recombinant manner.

18. Endoprosthesis according to one of Claims 15 to 17, characterized in that it contains muteins of fibro-blast growth factors.

19. Endoprosthesis according to one of Claims 14 to 18, characterized in that it contains acid-stabilized forms of the polypeptides.

20. Endoprosthesis according to Claim 14, charac-terized in that it contains in the porous matrix 1 ng/cm3 to 1 mg/cm3, preferably 1 to 100 µg/cm3, of polypeptide.

21. Endoprosthesis according to one of Claims 1 to 20, characterized in that it additionally contains one or more pharmaceutical active substances with an antibiotic effect.

22. Endoprosthesis according to Claims 1 to 21, characterized in that it is in the form of an implanta-tion kit which is ready for use and consists of two or more separate components, one component of which is a prosthesis shaped article which contains the porous matrix, and another component contains a liquid preparation of the polypeptide.