DE19945529A1 - Implant for reconstructing bone defects, useful in e.g. cranial, especially facial, area, consists of highly pure alumina and/or zirconium oxide bioceramic with coating having bone affinity, e.g. tricalcium phosphate or hydroxyapatite - Google Patents

Abstract

Implant for reconstructing bone defects, preferably in the cranial area, consists of a highly pure bioceramic of alumina and/or zirconium oxide, the surface of which is (partly) coated with substances having an affinity for bone, e.g. tricalcium phosphate or hydroxyapatite.

Description

The medical need for the implants to be used is increasing in frequency and Number has increased significantly for some time. The replacement of deformed hip joints through an implant to increase mobility restore affected patients to a large extent. For those with treatment of surgeons responsible for bone defects, mainly plastic Surgeries in the skull area, there is currently no suitable procedure for individual implants made for the application Functional security. So far, some metals, various plastics, glass, Ceramics and the various combinations of these materials applied. For plastic surgery, mainly in the face and skull area, could in in most cases only metal implants are used, but because of Part of significant symptoms of intolerance after some time due to a complex second operation had to be removed again. The above Materials, especially the metals, are not biocompatible in the desired way. With most implants there are fundamental differences between the mostly mechanically changing forces of the core and the surface structure. This consideration suggests that coating with a bioactive material is fundamental since chemical and physical reactions take place run off the surface. Fundamental for biological interactions Hydrophilic and hydrophobic are important for the required bone replacement Groups, the crystal structure, surface charges (polarity) and the roughness. Biocompatibility is an important factor for the compatibility of an implant crucial requirement. Suitable for the surgeon is very difficult Implants to replace the sometimes very irregularly limited Preserve bone defects on time and also in terms of costs.  

The basic object of the invention is a custom-made implant ready to build bony defects in the human skeletal system places, especially for reconstructive surgery of the skull area, but also the remaining parts of the skeleton. Basically, the production is relative is easy to implement and therefore maximum biological compatibility as well ensures optimal integration into the bone tissue.

In order to achieve a solution to this problem, the invention provides as Bioceramic implant material made of aluminum oxide and / or zirconium oxide use, the interfaces of the implant specifically one for the Get bioactive coating application.

A material that is absolutely bio-inert is best suited for the implants used: high-purity aluminum oxide. With the designation according to IEC 672 and DIN 58835 with a share of <99.7% aluminum oxide, there is an implant material that has been recognized worldwide since 1974 and has been used clinically successfully. Through numerous studies, this material has proven its biocompatibility. The biocompatibility can be explained as follows: In the aluminum oxide molecule, the strong chemical bond between the aluminum and oxygen ions is the basis for maximum corrosion resistance; due to its high purity of aluminum oxide, the implant cannot undergo any chemical reactions, it is bio-inert.

Note: Already in mid- 1985 there were own investigations as part of a medical activity at the eye clinic of the University of Erlangen-Nuremberg: (Mayer, Bohmann et al .: Reaction behavior of implants made of aluminum oxide in comparison with previously used plastics on fibroblast cultures. Poster contribution for a scientific symposium of Eye Clinic of the University of Erlangen-Nuremberg, 1986)

By examining the biological behavior in the tissue with the bioceramic implant material aluminum oxide compared to plastics the excellent tissue compatibility is impressively confirmed. Further  new insights into the influence of the surface quality obtained from implants made of oxide ceramics.

Of outstanding importance in addition to the use of high-purity oxide ceramics made of aluminum oxide or zirconium oxide - the use of zirconium oxide because of would be preferable to its higher hardness, but only for special purposes is suitable because the production is significantly more complex and expensive than the proven Aluminum oxide is a surface that is specific to the application possible coating with bioactive materials e.g. B. tricalcium phosphate or may preferably have hydroxyapatite. Both new bone formation as well the regeneration of the bone to be connected can be affected by the action of BMP (Bone Morphogenetic Protein) and growth factors on the attached Bone cells can be controlled. BMP has been genetically engineered in for ten years recombinant form. Clinical trials are ongoing in several countries Trials of BMP and growth factors in the treatment of Bone defects. Clinical studies help clarify the coating of Implants of the BMP and growth factors induced Bone growth.

The structure of the human bone consists of 50% mineralized Calcium phosphate, 25% from organic compounds and 25% from water. The predominant part lies in the mineralized phase of the bone Hydroxyapatite before. Hydroxyapatite can also be synthesized via precipitation reactions manufactured and carbonates and fluorides in the crystal are replaced. In the for the past twenty years, B. very successful with titanium hip joints coated hydroxyapatite and tricalcium phosphate implanted. With that became a substantial improvement of the border connection between implant and hard tissue achieved. The Coating the implant from an oxide ceramic (aluminum oxide and / or Zirconium oxide) especially with hydroxyapatite or BMP gives the great advantage that the adjacent bone particularly quickly to the interface of the implant growing up. The surface coating of the implant is determined by the Bone cells recognized as the body's own raw material, because the bone substance to predominantly consists of the identical material, which means that  Considerable growth in terms of duration and durability is improved. The bioactive coating takes over at the beginning of the Healing process exclusively the function of bioactivity. The coating can be microscopically thin on the implant, it does not have to be complete be flat, which simplifies the manufacturing process. Through this The body's own cells are able to coat the implant quickly adapt. They partially dissolve the superficial calcium phosphate and convert it to hydroxyapatite if collagen is present, whereby it turns out to be Firmly attach the new bone layer to the oxide ceramic. The result is one rapid coupling of implant with bone structures to be integrated. At previous oxide ceramic implants are not yet a coating for one improved and accelerated healing. To secure the implant anchoring until complete waxing is one of them Known screwing suitable, this screwing according to the invention using ceramic screws, especially ceramic screws Zirconium oxide can be performed. The zirconium oxide ceramic screws are extremely hard and tough, so that there is a risk of breakaway when implanting as well as practically excluded during the healing phase. Just like the oxide ceramic implants, the screws should have a Surface coating should be provided so that they are very fast in the same way be integrated into the adjacent bone structure. The invention Implants and the additional screws required in the application, can remain completely in the body because of their bioinertness in no way cause negative influences, not even in long-term use become.

In the further embodiment of the invention, the surface coating can be a Antibiotic can be added, either as an admixture or as an additive another coating can be applied. The additional application of Antibiotics for surface coating brings the decisive advantage that Bone injuries with larger wound openings are almost always bacterial Contamination is present, which can thus be significantly reduced.  

The antibiotic to be selected for the coating can be used before the operative Intervention can already be administered intravenously to the patient. This could be optimal the integration of the implant is secured with the same "on-site coating" and not be disturbed by additional unnecessary inflammatory processes, since sufficiently high concentrations of antibiotic substances at the interfaces available.

Another feature of the invention is the surface structure of the oxide ceramic Implant, the crystal structure through the ceramic manufacturing process so was designed so that post-processing is unnecessary (surface energy of the Implant interface due to randomly arranged crystallites during the Sintering process). As a result, the growth of the bone cells on the Implant favored to the interfaces. (Results of own investigations, see citation note)

The implants according to the invention see a further preferred improvement before, since it has a kind of "honeycomb" structure, resembling the porous Internal structure of the natural bone. Can be achieved this, for example, in that the implant consists of several open partial chambers is put together into a common unity. The surface of the implant is closed to the outside, with the corresponding Surface quality, but there are enough cavities inside available, which make the implant is much lighter than in complete construction without pore spaces and inner chambers. An improvement, This is especially the case with larger bone defects in the skull area lower weight and thus increased patient acceptance.  

The implants described above can have a wide variety of shapes exhibit. Bone structures can also be replaced by plates tubular structural elements, for example when replacing long bones. However, there are particular difficulties in transferring the Implant training according to the invention for filling bone holes, if, for example, tumors peeled out of the bone are removed and then larger cut-out bony cavities remain.

Since the insertion of a filling implant according to the present invention, especially with small cavities, only with increased technical effort is possible, as a further addition to the invention, there is that to be formed Implant can be formed from coated oxide ceramic particles, which can be Comprehensive, viscous collagen substances at body temperature (approx. 37 ° C) elastically formable hydrogel can be embedded. The oxide ceramic particles that Sizes from less than 1 mm to a few centimeters and one preferably have increased surface shape due to the crystallite structure a good possibility of attachment of the healthy bone cells. They will Use first coated accordingly and then immediately with the Hydrogel blended so that it fits into the bone hole to be filled can be introduced.  

Another procedure is that the coated oxide ceramic particles in Gelatin sponges are embedded, which one has already been timed to has used limited filling of the bone defects, taking the small ones Gelatin sponges in turn through the malleable hydrogel are held together when they are pressed into the bone defect. Compared to the previous use of such gelatin sponges, which after to be absorbed by the body for a short time has the invention Procedure has the decisive advantage that not one in the resorption the gelatin sponge is the only major bone defect remaining what has to grow slowly from the surrounding bone cells Experience has shown that only with relatively small and stable defects can take place successfully. The bony defect is caused by the Filled with oxide ceramic particles, this coated ceramic conglomerate offers one optimal opportunity for the body's own cells through the surface growth of the Divide with each other and with the walls of the bone defect into one to unite the new bone structure. Notwithstanding that the Oxide ceramic particles arranged directly on the wall of the bone defect with hydroxyapatite or other bone-affine coatings Another incentive is to stimulate the growth of the body's own cells Advantage that purely in terms of volume only a much smaller cavity the body's own bone cells must be newly created to ensure that the entire bony defect is completely restored. Most of the The cavity in the bone is already filled by the oxide ceramic. The The invention also relates to a method for the reconstruction of, preferably bony skull defects by inserting a prescribed implant, which is characterized in that about imaging processes, i.e. digitally obtained data from computed tomography X-ray and / or magnetic resonance imaging examinations a perfect fit Implant or a mold for casting an implant according to the measured defect is manufactured, which is then in the described way is coated.  

These procedures enable the surgeon to work with the manufacturer high-performance ceramics via telemedical data transmission for the Manufacturing of very precise implants. So that the manufactured implant then without major postprocessing and thus without further damage to the surrounding bone structures during the operation into the Defect site in the patient's body can be used Intermediate step provided before the final manufacture of the implant: The digital data of radiological imaging becomes a waxy one Model created in the so-called "rapid prototyping process". The surgeon can thus practically "re-enacting" the operating situation, changes to Wax models are possible without any problems. The data of the so changed Implant models are captured by a device with laser scanning and by Data transmission transmitted to the manufacturer's computer system. The computer of the high-performance ceramic implant manufacturer compares them telemedically transmitted, changed data of the wax model with the existing digital Radiologically acquired data and thus determines the exact shape of the implant to be manufactured. The described type of implant production with the help The imaging procedure applies to the fixed implants mentioned at the beginning. But implants formed from oxide ceramic conglomerates can also be used this way can be adapted to a certain complicated shape, using additional bio-inert putties used at body temperature are no longer plastic, so that the implants retain their shape and therefore also can not only be used for filling bone defects.

Further advantages, features and details of the invention result from the following description of an embodiment and based on the Drawing.  

Show:

Fig. 1 is a schematic image of the bony structures of a human skull with the possibility of treating bone defects,

Fig. 2 is an enlarged detail in the region of a hole-shaped defect in the lower jaw along the line II-II in Fig. 1, and

Fig. 3 of an oxide ceramic particle (3 times enlarged view), which is used when filling as an implant for the defect in Fig. 2.

In Fig. 1, the bony parts of a skull are shown schematically, which is badly damaged on the left side by an injury, on the assumption that the bone part 1 including the broken parts of the adjoining bone fragments 2 and 3 are replaced by an implant should. For this purpose, an imaging process, e.g. B. high-resolution computed tomography or nuclear spin diagnostics in all three dimensions digital data acquisition of the defect area. With this imaging diagnostics it is possible to find the necessary convexity (curvature) of the failed bone parts automatically by the computer by means of a corresponding adjustment to the neighboring regions, even if the part is missing. If necessary, the opposite, non-injured position on the other side of the skull can be measured and its curvature, bone thickness and other data for the production of the missing piece of bone can be used for the contour determination. From the data obtained, which are transmitted to the responsible doctor by telemedical technology, the procedure for manufacturing with the ceramic manufacturer can then be passed on using the new medium telemedicine. The ceramic technology of data processing is thus able to either mill out the corresponding part from an oxide ceramic block or manufacture it fully automatically using a laser by means of ablation, using the possibly modified data of "rapid prototyping".

In most cases, however, this data will first be used to form a part made of a suitable material, which is then used to produce a mold in which the actual implant is manufactured by high-temperature injection molding. The ceramic manufacturer will of course include the shrinkage (a few percent) that occurs during the manufacturing process in the raw data. The ready-to-fit implant consists of a bio-ceramic made of aluminum oxide and / or zirconium oxide and can be coated on its surface with various bone-related substances. When coating the adjacent osseous structures with hydroxyapatite, this only takes on the function of bioactivity at the beginning of the healing process. The coating can be microscopically thin on the implant, it does not have to be completely flat, which simplifies the manufacturing process. This coating enables the body's own tents to quickly adapt the implant. They partially dissolve the superficial calcium phosphate and convert it to hydroxyapatite if collagen is present. The result is a quick coupling of the implant to the neighboring bone structures. For implant anchoring there is also the option of a permanent connection with a bone screw made of the same bioceramic material. Instead of a bone fixation using ceramic bridges, preferably using zirconium oxide screws, which may interfere with the operation, a novel, biodegradable film can be applied over the implanted bone parts. It is an organic product with the name "MacroSorb PS". The film consists of lactic acid and can be heated to 55 degrees and placed like a modeling clay on the bone filled in with the implant ( Fig. 4.1). The film hardens when it cools down to body temperature. Similar to a previously used metal grid, the film protects the bone implant from neighboring tissue parts such as muscles or fat, which could interfere with the healing process. Since the film is made of lactic acid, it will have completely dissolved in about a year or two, when the implant has long been firmly anchored in the bone. Unlike in many cases with disruptive metal screws or metal grids, no second operation to remove these aids, which serve as protective barriers, is necessary. Another advantage for use during surgery with the help of lactic acid film is that the numerous pores in the film cause blood vessels, bone-forming cells and nutrients to migrate, thereby accelerating bone growth. In Fig. 2 and 3, the construction of an implant is specifically designed to detect for filling bone holes. Such a bone hole 6 in the lower jaw 1 , which has arisen, for example, by scraping out a tumor or the like, is filled according to the invention with an implant which has not been made externally as a whole component but has been prepared by the surgeon himself, a large number of oxide ceramic granules being used . The term "granulate" is not to be understood specifically to mean that it is also a matter of parts which have arisen from "granulation". It can also be small, by casting or the like, for. B. act pressed particles, as one of them with the reference numeral 7 is shown enlarged in Fig. 3. These granules 7 with dimensions of, for example, 1 × 1 to 2 × 2 mm, made of high-purity ceramic made of aluminum oxide or zirconium oxide, are provided with a surface coating, preferably of hydroxyapatite, and then embedded in gelatin sponges of dimensions, for example 1 × 1 × 1 cm. These gelatin sponges 8 are mixed together with a viscous hydrogel which can be plastically formed at 37 ° C. and pressed into the bone hole 6 so that they completely fill it. With the absorption of both the hydrogel and the gelatin sponges, the body's own cells reach the relatively densely packed granules 7 and grow there as new bone cells, so that there is a connection of these granules with each other through living bone mass as well as with the inner wall 9 of the bony defect 6 . However, the oxide ceramic particles can also be enclosed with the lactic acid film described above and the bone hole can be modeled with it. With relatively little of the body's own bone mass, a relatively large bone hole can thus be filled in such a way that a biocompatible polycrystalline structure is created which can remain permanently stable without discomfort for the patient.

Claims (13)

1. Implant for the recovery of bone defects, preferably in the skull area, characterized in that it consists of a high-purity bioceramic made of aluminum oxide and / or zirconium oxide, the surface at least partially with bone-affine substances, for. B. tricalcium phosphate or hydroxyapatite is coated. 2. Implant according to claim 1, characterized in that the surface Contains antibiotics and additional growth factors can. 3. Implant according to claim 1 or 2, characterized in that it is a Surface which is characterized by the crystallite structure as "rough" is. 4. Implant according to one of claims 1 to 3, characterized in that it has a physiologically necessary pore-like inner structure. 5. Implant according to one of claims 1 to 4, characterized in that it from several precisely fitting parts to a finished implant is composed, with open, pore-like cavities inside. 6. Implant according to one of claims 1 to 4, in particular for filling in Bone cavities, characterized in that it consists of a coated Granulate is molded into a viscous plastic mold at 37 ° C Hydrogel is embedded. 7. Implant according to claim 6, characterized in that the coated Ceramic particles are embedded in gelatin sponges by hydroget be fixed.   8. Implant according to claim 6, characterized in that the coated Granulate particles into a plastic, bioactive film that can be formed at 55 ° C Lactic acid can be modeled. 9. Implant according to claim 6, 7 or 8, characterized in that the Granules a preferably non-circular shape with a rough, a good one Anchoring option for surface resulting in bone cells exhibit. 10. Implant according to one of claims 1 to 9, characterized in that it is provided with holes for anchoring screws. 11. Implant according to claim 10, characterized in that the Anchoring screws are made of zirconium oxide ceramic. 12. Implant according to claim 11, characterized in that the Anchoring screws with tricalcium phosphate, bone affine Growth factors or preferably hydroxylapatite are coated. 13. Method for the reconstruction of, preferably bone defects of the Facial skull, by inserting an implant according to one of the Claims 1 to 11, characterized in that the Data transmission using telemedical procedures Bone replacement enabled and via the intermediate step of the "Rapid Prototyping "an implant or a mold for casting an implant digitally on prepared data according to the measured defect is manufactured, which is checked for accuracy of fit before insertion is coated.