WO2006039733A2

WO2006039733A2 - Bone replacement part comprised of continuous fiber composite material

Info

Publication number: WO2006039733A2
Application number: PCT/AT2005/000405
Authority: WO
Inventors: Thomas Zischinsky
Original assignee: Mediceram Chirurgische Implantate Gmbh
Priority date: 2004-10-12
Filing date: 2005-10-11
Publication date: 2006-04-20
Also published as: WO2006039733A3

Abstract

The invention relates to a bone replacement part (6) in which, in order to increase the strength while simultaneously being able to be machined by using conventional medical devices and having an elastic behavior similar to that of bones, and while having a high tolerance to damage, and the ability to be shaped individually. This bone replacement part is made, in essence, of a ceramic composite material (CMC) consisting of an essentially ceramic, in particular, oxide-ceramic matrix (2) and of essentially ceramic, in particular, oxide ceramic continuous fibers (1) embedded therein.

Description

BONE PARTS

The attempt to stabilize or replace biological bones by means of surgical bone replacement materials made of different natural or synthetic materials is very old. The reconstruction of bone defects after accidents, tumor resections, diseases or malformations as well as the stabilization of fractures are based on the respective function and medically justified. Likewise, the reconstruction of the bone should also serve to restore harmonious contours and thus aesthetic rehabilitation. An ideal and long-term stable design is sought. The stabilization of a bone fracture should enable and accelerate bone healing and functional rehabilitation.

According to the state of the art biocompatible, bioactive and absorbable (biodegradable) materials are used as a bone substitute. The biocompatibility of a material is achieved by the material is not recognized by the body as an impurity and fought or degraded by the immune system. Bioactive materials have the property that they stimulate the cells responsible for the formation of new bone, the osteoblasts, and thus support ingrowth. Resorbable materials disintegrate into small components after implantation and are excreted naturally.

The prior art includes stainless steel (US 2003171820), cobalt chromium and titanium alloys, high performance ceramics, especially alumina (Al ₂ O ₃ ) and various polymers with and without bioactive coating to the biocompatible materials. Hydroxylapatite (US 5759376, US6689375), calcium phosphate (CA 2354552, US 5766669, WO 03092760), calcium carbonate and glass ceramic (US 5074916) are known as bioactive substances for bone replacement and coating. Resorbable materials for bone replacement are various polymers (US Pat. No. 6,692,760), such as polylactide (PLA), polyclycolide (PGA) and collagen from foreign bone.

In the past two decades, titanium alloys and high performance oxide monolithic ceramics have become established as a material with tolerability for load bearing surgical bone replacement.

Thus, according to the prior art, virtually all plates for the stabilization of fractures of titanium with and without bioactive coating (US 6702855). They are manufactured in different standardized sizes and shapes including mounting holes for attachment. For the treatment of bone defects, in particular in the skull, face and jaw area, lattices and perforated strips of titanium and lattices of resorbable polymers are known. They are manufactured in fixed standard sizes. The adaptation to the contour of the healthy bone and the modeling to restore esthetic forms are made by the surgeon during the operation. The attachment is usually by screwing through the already existing plurality of holes (punched tape) or passages (grid) in the material. The holey or lattice-like surface structure supports the healing with the healthy bone.

Furthermore, according to the state of the art, custom-made plates made of titanium and monolithic glass or high-performance ceramics are used to supply bone defects, in particular in the area of the skull and face. In contrast to the surgical implants already mentioned, these are manufactured individually for each patient. Based on a computed tomography of the bone defect, the shape and mounting holes of the implant can be planned and manufactured. This happens before the operation and thereby shortens the operation time. By customization, better functional and aesthetic results are achieved.

In recent years, porous materials having bone-like properties have been known. They consist of both biological bones (US 2004059422), as well as synthetic bioactive substances such as hydroxyapatite or tricalcium phosphate (US 2004057939). In monolithic form, they are not suitable for load-bearing indications. To increase the strength of the material organic and inorganic short fibers are added (US 2003075822). The aim is to achieve an optimal balance between long-term stability and the stimulus of rapid ingrowth of bone-forming cells. These composites are usually available in defined forms as blocks or plates and can be individually processed during the operation. The porosity allows for optimal healing, which can be actively assisted in the simultaneous choice of a bioactive material, such as hydroxyapatite. They are usually used to fill cysts of similar bone defects. For fixation, resorbable membranes placed over the defect site are used.

The use of a body's own bone or cartilage as a bone substitute is also known and used. The body's own bone or Cartilage is usually removed from the rib or pelvis of the patient, prepared and implanted in the defect region.

Current studies and future plans aim to use different alloplastic materials as carrier substances (DE 10100961) for growth factors. With the help of such bone enhancement, the current standard of bone defect correction is to be replaced by autologous (own) bone transfer.

If several materials are combined in one material, composites are created. These can be composed of different material groups or of the same material group. Depending on the nature of the surface structure and density, compact, microporous and highly porous composites with short or long fiber reinforcement are known as surgical implants. As a medical bone replacement material long fiber reinforced composite materials are known in the art, which consist mainly of carbon fibers and a matrix of thermoplastics or thermosets.

Furthermore, composites are known as bone substitutes from combinations such as PLGA / HA, PHB / HA, lactide and glycolic acid composites with calcium and magnesium phosphate, PE / HA, PLLA / HA, and bioglass / HA.

The material properties of the known surgical bone substitute materials are very different, but have great deficits in certain areas. The ideal material for stabilizing and reconstructing biological bone should meet the requirements of biocompatibility, corrosion resistance, high strength and stability over a longer period of time with simultaneous elasticity, porosity, formability, sterilization resistance, ease of fabrication and reprocessing in the operating room, damage tolerance and affordability.

Due to the smooth surface or the lack of high porosity despite Oberflächenpdifizierung of trauma surgical plates made of steel, titanium and monolithic high-performance ceramics has proved disadvantageous that they grow poorly with the biological bone. This can lead to a loosening over time, especially with continuous load cycling - the surgical implant has to be revised.

Furthermore, all metals such as steel are not computed tomography (CT) / magnetic resonance (MR) compatible, ie there are considerable artifacts (artifacts) on the sectional images of a CT / MR examination during the images by reflections. Depending on the scope of these artifacts, answering the impede difficult diagnostic questions, or in the extreme case even completely impossible.

The mechanical processing for shaping and meeting the accuracy of fit of surgical implants is costly because of the hardness of pure titanium and monolithic high performance ceramics. Furthermore, because of the brittle fracture behavior of monolithic high-performance ceramics, only thicker wall thicknesses can be produced, which results in a higher weight and a higher mass inertia. This has a detrimental effect on stable fixation with healthy bone, minimizing micromotion in the interface area and restoring aesthetic contours.

Monolithic high-performance ceramics do not allow plastic deformation. Instead, local stress peaks cause defects to crack. This has the disadvantage that even minor mismatch between biological bone and bone replacement in the support area can not be bridged by tension of the bone substitute. As a result, the bone substitute is not uniform, it heals badly and can loosen over time.

Custom-made bone substitutes made of titanium or monolithic high-performance ceramics can no longer be reworked during operation with conventional medical tools and devices. If the bone substitute can not be adequately fixed due to an unforeseen defect situation with the prefabricated mounting holes, or if mechanical tensions occur and thus the fracture has failed due to the low ceramic damage tolerance, the operation has failed.

Porous materials can be used according to the current state of the art despite admixture of short fibers for reinforcement only conditionally for load-bearing indications. Their strength is far below that of compact materials or composites.

Formable grid and punched tape as a bone substitute on all sides have a sharp-edged surface structure. It is known that this can lead to immune reactions usually in the form of inflammation of the surrounding tissue.

The use of an autogenous bone or cartilage as a bone substitute also results in impairments of the donor site located in another body region. Furthermore, the amount of available material is limited. The transplantation and disassembly of transplanted bone

- A - or the elastic deformations of cartilage represent unpredictable effects. It is known that this technique can lead to complications that usually leads to a removal of the transplanted bone or cartilage.

The supply of bone defects by means of allogenic (human alien) or xenogeneic (animal) bone transfers can meet the requirements of the reconstruction of complex forms badly in the prior art. Furthermore, there is an increased risk of infection from allogeneic or xenogenic foreign bone.

The resorbable implants of predominantly polymers currently used in practice have such disadvantages that they repeatedly lead to inflammations and fistulas or are not stable enough to heal complicated or larger bone defects. Furthermore, it has not yet been sufficiently researched which biological requirements resorbable implants have to satisfy during bone healing, and in particular which influence the absorbed substances have on the human organism.

It is known that bone substitutes made of long fiber reinforced composite materials, which consist predominantly of carbon fibers and a matrix of thermoplastics or thermosets, can trigger inflammation of the surrounding biological tissue. This can be caused by released carbon fiber particles (fragmentation) and by mechanical irritation. The issue of biocompatibility of carbon fiber composites as bone substitutes is therefore a hot topic. Some experts credit biofibers for carbon fibers, but many are critical of them.

In contrast, the invention is based on the object to find a biocompatible bone substitute for surgical implants for the stabilization and reconstruction of biological bone, in particular high strength over a long period of time with simultaneous workability with conventional medical devices and elastic behavior, at the same time high damage tolerance and custom formability equally well met.

This is achieved in that the bone replacement part consists essentially of ceramic composite material (CMC), consisting of a substantially ceramic, in particular oxide ceramic, matrix and embedded therein substantially ceramic, in particular oxide ceramic, continuous fibers. Ceramic composites (CMC) have a quasi-plastic behavior. This property allows low fitting tolerances in the interface area between biological bone and bone replacement part by clamping the same by means of the surgical screws to bridge. This stable support of the bone replacement part is a prerequisite for a secure screw connection even over a long period of time. Furthermore, by ensuring a good contact between biological bone and bone replacement part, the healing is promoted. Ceramic composites (CMC) have an exceptionally high damage tolerance that eliminates the brittle fracture behavior that exists, especially with monolithic ceramics. This allows the surgeon to perform through holes for fixation elements (eg screws) or shape adjustments of the bone replacement part with common medical devices even during surgery. The high damage tolerance additionally reduces the risk of fracture if the bone replacement part is overloaded after implantation.

In a particular embodiment of the invention can be provided that the main component of the ceramic composite material (CMC) alumina (Al ₂ O ₃ ) is.

Monolithic high-performance ceramics based on high-purity alumina have proven to be particularly biocompatible material with high corrosion resistance in many medical applications. Alumina (Al ₂ O ₃ ) has been successfully implanted tens of thousands of times, especially as part of hip joint prostheses.

In a further embodiment of the invention it can be provided that the oxide-ceramic continuous fibers in a thickness of 0.05 to 1 mm, preferably from 0.2 to 0.5 mm, as a two or three-dimensional fabric or as a braid or as adjacent loops in the matrix embedded in one or more layers in the same or different directions.

Ceramic composite materials (CMC) possess embedded fibers despite porous matrix even at low wall thicknesses (eg 0.8mm) enormous strength. This strength is sufficiently high for many medical applications, especially in the skull and face area. The small wall thickness has the advantage that after implantation aesthetic contours are not impaired and the bone replacement part according to the invention is barely palpable, in the area where this rests on the biological bone. Furthermore, has the thin-walled inventive bone replacement part a low weight. This has the advantage that micro-movements, caused by the inertia of the bone replacement part, are minimized. The minimization of these micro-movements in the interface area between bone replacement part and biological bone is a prerequisite for optimal healing. Depending on the type of tissue, tissue layers and fiber orientation, the anisotropic quasi-plastic behavior of the bone replacement part according to the invention can be adjusted such that, based on the elasticity, bone-like properties result. This is particularly important in load bearing indications of great importance to ensure the physiological introduction of the loads in the bony implant bearing. This elastically bone-like behavior prevents fracture of the biological bone, especially during load changes in the implant bed.

In a particular development of the invention, provision may be made for the bone replacement part to comprise at least one healing-promoting interface area for better healing in the biological tissue.

When using bone replacement, the aspect of rapid functional rehabilitation is of great importance. The patient should regain full mobility as soon as possible after implantation. Therefore, an accelerated osteointegration is sought. This can be achieved by modifying the area of the surface of the bone replacement part according to the invention that is in contact with the biological bone (interface area) in a manner that promotes healing. In particular, it can be provided that at least one of the at least one healing-promoting interface region has a porosity, pores having an average pore diameter of 50-500 μm, in particular 100-300 μm, the pores not being connected to one another or partially or wholly.

In order to promote osteointegration, the bone replacement part according to the invention is made porous in the interface region in order to achieve Ostekonduktivität. This guardrail effect facilitates the ingrowth of capillaries, perivascular tissue and bone cells. In the case of interconnective pores, the bone cells can grow through the interface region of the bone replacement part according to the invention.

Finally, it can be provided that at least at least one of the at least one healing-promoting interface region has at least one bioactive substance, in particular hydroxylapatite (Ca ₅ [OH (PO ₄ ) ₃ ]) or tricalcium phosphate (Ca ₃ (PO-O ₂ )).

In order to promote and accelerate osteointegration, the interface region of the bone replacement part according to the invention is bioactively modified with bone-building substances. The resulting osteostimulation stimulates bone metabolism by activating already differentiated bone cells.

In the following, particular embodiments of the invention are illustrated by means of figures. This shows

1 shows a cross section through a ceramic composite material (CMC), Figure 2 shows a cross section through an implanted form of the bone replacement part according to the invention, and

3 shows a section of a healing-promoting interface region of the bone replacement part according to the invention located in the early stage of healing.

FIG. 1 shows the section of a ceramic composite material (CMC) with a single-layered fabric of continuous fibers 1 embedded in a matrix 2. The continuous fibers may in this case be in a thickness of 0.05 to 1 mm, preferably of 0.2 to 0.5 mm, be embedded as two or three-dimensional fabric or as a braid or as adjacent loops in the matrix in one or more layers in the same or different directions. Depending on the type of fabric and fiber direction, the anisotropic deformation behavior can be changed and adapted to the biomechanical requirements. The fibers inhibit the crack growth of the ceramic matrix and allow for high damage tolerance, which facilitates processing. This is particularly important for manual post-processing by the surgeon to reduce fit tolerances between a prefabricated bone replacement part and the biological bone. Particularly valuable properties of fiber-reinforced ceramics are also the low density, high strength, high temperature resistance. Because of different requirement profiles exist a variety of material variants, which differ mainly by the type and amount of fibers, the nature and composition of the matrix materials, the structure of the fiber reinforcement and the applied manufacturing technology. According to the current state of the art, they are used in particular in the air and Aerospace, applied in engine technology, chemical apparatus construction and furnace construction.

The main component of the ceramic composite is preferably alumina (AbO ₃ ). But other biocompatible ceramics could be used. In particular, partially stabilized zirconium oxide (ZrO ₂ ) and bioglass ceramic should be mentioned here. Alumina (Al ₂ O ₃ ) suitable for medical use is highly pure and has a content of more than 99.5% by weight. Under normal conditions, ie at temperatures below 1000 degrees Celsius, aluminum oxide does not give off any ions in any environment. A release of ions is a prerequisite for a chemical reaction with the environment or corrosion. Aluminum oxide is chemically inert, ie extremely resistant to corrosion and bioinert with respect to the human body. The described materials can be used for the matrix, for the fibers or for matrix and fibers. For example, alumina (Al ₂ O ₃ ) can be used for the fibers and / or zirconium oxide (ZrO ₂ ) for the matrix or the reverse material combination can be used. Likewise, the same material, alumina (Al ₂ O ₃ ) or zirconium oxide (ZrO ₂ ) can be used for matrix and fiber. Another variant for the choice of material is silicon oxide SiO ₂ for fiber and / or matrix. Likewise, the matrix or else the fiber may consist of the two or three materials aluminum oxide (Al ₂ O ₃ ), zirconium oxide (ZrO ₂ ) or silicon oxide SiO ₂ .

FIG. 2 shows a cross-section through an implanted form of the ceramic composite material (CMC) 6 according to the invention with an interface region 5 which induces heat (bearing area between biological bone 3 and bone replacement part 6). The bone replacement part 6 is executed in the form shown by means of different wall thicknesses as coverage with bone defect filling of the Os Parietale. Other forms may be overlaps without bone defect filling, for example in the region of the midface or sleeves for bridging tubular bones after, for example, tumor resections. In the interface area 5 of the bone replacement part 6 with surgical screws 4 is firmly connected to the biological bone. Due to the quasi-elastic behavior of the ceramic composite material (CMC) 4 tolerance tolerances in the interface area can be bridged by means of slight tensioning of the bone replacement part 6 with the surgical screws 4. This ensures contact with the biological bone. Depending on the orientation and layers of the fibers 1, a anisotropic elastic bone-like behavior of the bone replacement part 6 according to the invention can be adjusted. This is particularly important for load-bearing indications to ensure the physiological introduction of loads into the bony implant bed. This prevents a rupture of the biological bone 3 in the implant bed. Due to the high strength of the ceramic composite material (CMC), the bone replacement part 6 in the interface region 5 can be made thin-walled. As a result, he is barely touchable from the outside and harmonic contours justice. By means of suitable manufacturing processes, the ceramic composite material (CMC) can be shaped specifically for the patient and thus fulfills an aesthetic rehabilitation.

FIG. 3 shows a schematic detail of a healing-promoting interface region of an implanted bone replacement part according to the invention located in the early stages of healing. The healing-promoting interface region may comprise pores or be modified with bioactive substances. The interconnective pores 7 can also be modified additionally with a bioactive substance, in particular hydroxyapatite (Ca ₅ [OH (PO ₄ .4) ₂ ] or tricalcium phosphate (Ca ₃ (PO ₄ ) ₂ ) These substances belong to the group of calcium phosphate compounds All calcium phosphates are soluble depending on the pH value, in contrast to the bio-inert, insoluble aluminum oxide (AI ₂ O ₃ ), which interacts with the body.The solubility or absorbability is linked to the acceptance in the body, base , the bioactivity that stimulates bone growth in the direction of hydroxyapatite (Ca ₅ [OH (PO ₄ ) ₃ ]) or tricalcium phosphate (Ca 3 (PO ₄ ) 2) The pores provide the bone cells with an anchoring possibility in the micro region, where pores have an average pore diameter of 50-500 .mu.m, in particular from 100 to 300 .mu.m, wherein the pores are not or partially or completely connected to one another allows the collagen fiber bundles 8 the continuous vascular development of the interface area. Bioactive substances in the pores stimulate bone metabolism and prevent the ingrowth of connective tissue. Gradually the bioactive substances are absorbed and at the same time braid bones form the interstices. It creates a solid biological connection between bone replacement and healthy bone.

Claims

CLAIMS:

1. bone replacement part (6), characterized in that it consists essentially of ceramic composite material (CMC), consisting of a substantially ceramic, in particular oxide ceramic, matrix (2) and embedded therein substantially ceramic, in particular oxide ceramic, continuous fibers (1) ,

2. bone replacement part (6) according to claim 1, characterized in that the main component of the ceramic composite material (CMC) or the matrix (2) or the continuous fibers (1) alumina (Al ₂ O _3, ) and / or zirconium oxide (ZrO ₂ ) and / or silicon oxide (SiO ₂ ).

3. bone replacement part (6) according to claim 1 or 2, characterized in that continuous ceramic fibers (1) in a thickness of 0.05 to 1 mm, preferably from 0.2 to 0.5 mm, as a two or three-dimensional fabric or as Braid or as adjacent loops are embedded in the matrix in one or more layers in the same or different directions.

4. bone replacement part (6) according to one of claims 1 to 3, characterized in that the bone replacement part (6) comprises at least one healing promoting interface area (5) for better healing in the biological tissue.

5. bone replacement part (6) according to claim 4, characterized in that at least one of the at least one healing promoting interface region (5) has a porosity, wherein pores (7) have an average pore diameter of 50- 500 .mu.m, in particular 100-300μm, wherein the pores (7) are not or partially or completely connected to each other.

6. Bone replacement part (6) according to claim 4 or 5, characterized in that at least at least one of the at least one healing promoting interface region (5) at least one bioactive substance, in particular hydroxyapatite (Ca ₅ [OH (PO ₄ ) 3]) or tricalcium phosphate (Ca ₃ (PO ₄ ).?).