JPS62501132A - bone substitute material - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Bone substitute materials and their uses TECHNICAL FIELD The present invention relates to bone substitute materials and methods of use thereof.

Attempts are always made to fill gaps in bone caused by bone damage or surgical removal. Ru. This is because experience shows that bone regeneration takes a long time, and that bones are not completely healed. The function of the tip will not be restored until it is removed. Sea urchins recover their original function through large bone gaps. Healing is almost impossible. This allows the bone substitute material to be in-blended with the graft material. This is why there have been attempts for a long time to use it as one of the tools.

Unfortunately, the search for suitable materials has been very ineffective. Zero-source materials (e.g. , from bone grafts from the same patient), only part of the motor system gives up the bone The amount of material that can be used for this purpose is limited. Homologous materials can be used to answer questions about immune responses. give rise to problems (problems that have not been solved to this day). I'm tired from the experiment, but I'm ready. Both homologous and heterogeneous bone materials can be used in limited quantities for bone grafting. However, it is not fully accepted by the body and is not fully combined within the body.

This processes animal bone to produce a bone substitute material that can fill and bridge gaps. This is the reason why attempts have been made to expand this field. The honeycomb structure of the bones is preserved as much as possible. It has always been assumed that

All methods and all commercially available materials are ``rchialit'' or rKie1 pieces. The minerals are removed, and foreign bone fragments called Prepare animal bone or other collagen from animals in such a way that it loses antigenicity. . The collagen thus obtained is bound to and absorbed by the body. but, It is not suitable for withstanding body mechanical forces and is not useful as a stable support structure. Not worth it.

This produces a material that has the properties of bone tissue, that is, it provides support and is resorbable. This is the reason why repeated attempts have been made to expand it.

Various sintered tricalcium phosphates or apatites are primarily used for this purpose. ing. Attempts to utilize the connection of whole-joint prostheses, for example, This is done by assembling the surface of the implant. The result of this prosthesis is This can be compared to ingrowth in materials used for bone graft implants. . This is because similar demands are made on the coating, structure and surface properties of prostheses. This is the reason. To date, the treatment of bone ingrowth and bone gaps has not been satisfactory. Not resolved. Assembled collagen-based bone substitute materials (e.g. DE-O32854490) does not show sufficient osteogenic effect. these The material indicates the structure that the bone should take, ie, the trabecular structure. This structure is reinforced This only results in the accumulation of thick trabeculae outside and inside, and does not allow for normal bone structure. moreover , due to demineralization, these materials no longer have mechanical strength, so osteoinduction , and has no supporting function. Sintered materials are mostly absorbed within their useful period. do not have.

The problems that arise in joint replacement are the same as those in bone replacement, but in addition, The problem is that the interface of the thesis receives a considerably greater load than the interface of the bone substitute material. Melt. A prosthesis, or artificial joint, typically has a stem (stem) with pins in the bone. fixed by the fixed section) or placed on the affirmative (Journal of Journal of Bone and Joint Surgery), No. 21 @ (1939), 269-2 (See page 88).

For example, a common method for replacing hip joints involves inserting an all-metal shaft into the bone marrow cavity. and fixing there with a two-component plastic (bone cement) (ibid., No. 42139 (1960), pp. 28-30).

However, known bone cements do not exhibit sufficient compatibility and biomechanical strength. this During the process, it is generally necessary to enlarge the surface of the prosthesis stem. this can be achieved, for example, by wavy or serrated surfaces (DE-PS 837 No. 294). DE-O82127843 discloses that the same metal substrate and solid A highly bonded porous metal coating is disclosed. This coating enlarges the surface and allows the inner growth of the bone. This is done to enable long-term development. In known coverings, bone ingrowth is It only happens under certain conditions. The surface of such a prosthesis has a reproducible (all It is not possible to obtain results that are transferable to all patients. Therefore, other factors may It serves to ensure growth and fixation for prognostic purposes.

The present invention allows for the induction of desired bone ingrowth and formation of supportive or non-supportive bone structures. Two main factors have been found that easily determine the morphology and the associated load-bearing capacity. Ta. These factors are (1) the morphology of the surface structure at the immobilization site, and (2) the chemistry of the surface. composition (chemical properties).

The extent to which individual osteoclasts and skeletal layers can be induced to form bone and specialized trabeculae To determine, experiments were performed using different morphological structures and chemicals.

Certain morphological structures in the fixation zone significantly induce bone formation by bone cells.

In contrast, different morphological structures provide the best support for remains cells by the remains cell layer. Becomes strongly formed. However, for optimal static results, in-branch The topography required for fixation of the components is taken into account in all designs. must be done. In addition, the overall load and the joint movements that work together also affect the force must be considered in connection with the design of the prosthesis, which is decisive for the introduction of

According to the present invention, the above-mentioned discoveries regarding bone formation and morphology as a shaping standard are achieved. Based on knowledge, four dimensions can be defined for the structuring of bone substitute materials. This 4 The dimensions are named from primary to quaternary structure. Based on this definition, the first order The structure is in the form of an external implant design, i.e. the fixation part of the prosthesis. be. Secondary structure represents the topography of the surface. The secondary structure is For example, surface shapes such as wavy or serrated surfaces or stepwise associated with the stem of a prosthesis. The purpose of these secondary surface structures is to provide mechanical rigidity. It is to support the fixed surface and to distinguish the fixed surface in relation to the load. According to this definition , the tertiary structure is the microstructure of the surface. The tertiary structure is a small sphere in the y, m range. including surface products such as Finally, the quaternary structure becomes a superstructure with a size of about 20 μm. Related.

DE-O82730004 teaches the fixation parts (particularly nails) of total bone prostheses. ing. Its surface consists of a number of interconnected parts connected to the substrate in one part and separated from each other. Shows protrusions. Its feature is that the space separating two adjacent protrusions is the highest between the surface and the protrusions. at least one narrow chi located at a height between the points.

The characteristics of this well-known fixation part vary from the prosthesis design (primary structure) to the microstructure ( tertiary structure), the latter being defined by surface protrusions. The purpose of this protrusion promotes cross-connection of bone tissue in the spaces between the processes, thereby allowing bone tissue to to enable more resistant fixation (preferably without the use of bonding materials) of Ru.

However, this known fixation surface formation exhibits drawbacks. i.e. remains cells and support does not exhibit optimal morphology for cortical bone and does not have shaping elements. moreover , this surface structure is not even partially absorbable. Therefore, to the substratum of bone cells The adhesion of is not as good as on absorbable surfaces. Additionally, bioactive effects and chemotactic effects (osteoinduction), especially in non-absorbable surface coatings. is mixed into the absorbent coating, it is not as large as in the absorbent coating. most Later, the microstructure on the surface of the anchoring part known from DE-O32730004 was Using a mixture of hemostatic agents, ashes material, antibiotics, vasoactive substances, bone-store hormones, etc. I can't do it.

The biggest drawback is that the surface structure does not allow the formation of a continuous supporting arch structure. be.

DE-OS 26 20 907 is an absorbable (based on calcium phosphate) Discloses coating of prosthetic stem consisting of ceramic material and non-absorbable plastic are doing. When the ceramic is absorbed, the continuous porous plastic structure Formed with bioactivated ceramic residue on the internal surface of the pores.

However, non-absorbent plastic matrices have drawbacks. In other words, plastic is , due to the shear forces occurring at the interface, and the wear material cannot be absorbed.

This can cause inflammation and cause the prosthesis to become loose. DE-O9262 Another major drawback noted in No. 0907 is that the absorbent ceramic particles This further reduces the overall absorbent capacity of the coating.

For this reason, the bone surrounding the prosthesis fixation area is deep enough to reach the base (supporting area). And they can't grow fast. This results in a decrease in strength.

The surface structuring of the fixed part of the stem prosthesis is described in US-PS No. 3 855 638. known from. A porous metal coating with a thickness of 100 to 20 μm is applied to a substrate of the same metal. is coated on. This coating consists of spherical metal particles with a size of 50 to 150 μm. , and those having pores with a size of 20 to 200 μm distributed between them.

However, US-PS 3 855 638 and US-PS 4 206 516 The size and distribution of the spherical forming elements described in No. 1 and 2 are not very effective.

The size of the forming elements for remains cells is less than 50 μM, preferably between 15 and It is 30 μs. The forming elements for the supporting trabeculae include a 500μ shoulder and a 1000μ shoulder. It is between. Size of non-absorbable forming elements in coatings described in the above-mentioned U.S. patents distribution does not allow rapid and sustained bone fixation. As shown in these patents In the above, the spaces allow for ingrowth of fibrous structures and even woven bone, but the upstream large voids It does not allow for the ingrowth and invasion of the mature supporting bone structure required for the stomach.

The problem of the present invention is to cover and surface structuring the bone implant and to The objective is to create a bone substitute material suitable for use as a bone substitute. This imblanc The bone must be deeply and rapidly penetrated by the supporting bone structure, thereby causing Produces a stable implant that can withstand loads. The problem is that the basic layer is reticulated It is said to have a structure and leave an almost ideal morphological space in its cavity system. The problem was solved by a surprising discovery. These spaces should be filled with absorbable filler (strong filled with a coating material consisting of a lucium compound (based on a lucium compound) and an absorbable binding substance. Ru. This induces bone ingrowth and formation of a supportive bony arch.

Therefore, it is an object of the present invention to provide basic structures surrounding interconnected and delimited spaces. Based on a three-dimensional support structure with body or forming elements and strong calcium compounds. A coating consisting of an absorbable filler and an absorbable binding substance (matrix) It is a bone substitute material. Furthermore, the object of the invention is to provide a complete bone substitute material of this kind. prosthesis, to Fixation parts for joint prostheses, covers for bone implants and joint implants. It is a closure material for caps, bone nails, and marrow cavities. Bone substitute material according to the invention The material exhibits both characteristic tertiary and quaternary structure. Therefore, the bone at the interface Not only does ingrowth occur, but the ingrowth columns grow together to form an arch. This also makes it possible to create a supporting bone structure.

The invention will be explained in more detail on the basis of the following figures.

Figure 1: Two spheres of quaternary structure forming the basis of a bone cell.

Figure 2 Schematic representation of a dense assortment of 3-order spheres with a 4-order spherical surface structure and bone Illustration of ingrowth.

Fig. 3 A covering having two spherical base bodies, a spherical filler, and a fiber-reinforced matrix Diagrammatic representation of.

FIG. 4 A view corresponding to FIG. 3 using stocking-like filler contained in the matrix.

FIG. 5 A diagram corresponding to FIG. 4 using a bead chain-shaped filler.

Figures 6 and 7: Bone replacement nail and medullary cavity closing material of the bone substitute material according to the present invention.

Figures 8 to 1O: Other embodiments and uses of the above materials.

First, the formation of a tertiary structure in the bone substitute material of the present invention will be explained.

A specimen consisting only of basic body layers of a specific size and shape is completely penetrated by bone. In fact, the bone structure in that cross section is almost indistinguishable from the sponge-like structure of physiology. That was a surprising discovery.

In particular, a layered spherical network with a size of 200 to 3000 μm is different from other coatings. It was found that the larvae also filled the spaces between the corpuscles with bone much more rapidly. Sara As a result, the most physiological supporting tertiary structure ('ri configuration method) is generated. . The expansion of the surface obtained in this way creates a huge surface that can withstand forces. arise. This surface follows an almost ballistic course with respect to the lines of force acting on it. Take.

A bone mass consisting only of a network of layered corpuscles and well adapted to the bone in terms of elasticity. The replacement material is completely penetrated by the bone in a very short time (12 weeks) and therefore Generates a permanent bone structure.

It has been found that such implants can withstand bending loads. this This is because the load is distributed over the entire surface. Huge surface area and resulting Due to the low mechanical loads, fatigue failures no longer occur.

The bone substitute material of the present invention further has the following advantages. The mass of the entire implant is The head weight of all commercially available prostheses is significantly reduced and therefore eliminated. be removed. This head weight can cause the prosthesis to loosen over time.

Edge phenomena and stress concentrations are avoided due to the preferred spherical structure of the basic body. Strictly across the bone surface represented by a mature bone structure with parallel fibers and a lamellar arrangement. The force is distributed uniformly.

Unlike full-stem prostheses, which are assembled by individual spheres at the surface, the present invention The layered network in the bone substitute material has a mechanical stimulation effect on the bone cells. . Does this indicate a bone structure capable of deep ingrowth? I can hear it.

Bone ingrowth is accelerated, especially when large and small balls are combined. 2・ Diameter ratios from I to 3:l are particularly good. - As an example, 200-1000μI (normal A sphere with an average diameter of 500 μl has a diameter between 800 μl and 3000 μl (average 10 μl). Can be combined with a ball with a diameter of 00μ shoulder). Small spheres preferably 300μm and 700μl The larger sphere has a diameter between, more preferably between 450μ and 550μπ Between 800μ and 2000μm, more preferably between 900μ2 and 1200μm with a diameter between The small and large balls each preferably have approximately the same diameter , for example 500 or 1000 μm. Bone accumulation consists of small spherical elements. It happens more rapidly. In contrast, the arch of the supporting bone is made of large spherical elements. formed around. All spheres are tightly connected to each other or at least mutually The fact that they are adaptable and flexibly connected to each other is consistent with the almost normal bone design. enables the generation of In this way, a permanent integration of the fixation part is formed between Becomes certain along with the marrow space of the vascular system.

A relatively rigid bond when each floor is in fixed contact with at least three adjacent balls. or occur. Depending on the structure of the supporting frames, each floor may contain more than three pieces, e.g. 1pl, 6@mafko can make solid contact with 8 neighboring balls, and this 1st piece has a solid frame. occurs. In the bone substitute material of the present invention, the basic body of the tertiary structure, preferably a sphere, is A system consisting of an absorbable organic polymer with a thickness from 5071i to 300 μm; One side with non-absorbable thread or wire of thickness from 100μm to 750μm or both, and are held together to form a three-dimensional bag of maximum density.

The basic body is preferably titanium, tantalum, cobalt, chromium, molybdenum, etc. their alloys, special steel-like metals and/or ceramics, apatite or TCP, and/or a mixture of two or more of these materials, and/or or of other inert materials. The base body is an absorbable material, e.g. polypep chloride, polylactate, polyglycol hydrochloride or their co-precipitates, gelatin, Substances from which quaternary structures are formed, such as collagen, calci as a matrix highly porous tricalcium phosphate as filler, Preferably from human apatite particles or particles from related calcium compounds It's good to have a lot of things.

Even if the weir body is not spherical, it is preferable to mix two weir bodies of different sizes. be done. Each of the diameters mentioned above is defined as an average diameter.

Spherical surfaces can be created as microstructures, which consist of spheres with a diameter of 15-30 μm. Alternatively, it may take the form of a spherical section such as a hemisphere.

In the bone substitute material of the present invention, the space in the tertiary basic body structure is filled. and/or the surface of the space is covered with a covering. Characteristics of this coating is completely absorbable (both matrix and filler).

The microstructure (tertiary) of the surface of the sphere, together with the characteristic covering (if present) , represents the quaternary structure (superstructure) of the bone substitute material of the present invention.

This coating (quaternary structure) will be explained in more detail below.

In one embodiment, the filler is 10 μ x hs et al. 20.0 μ summer (preferably Preferably, from 15 μl to 50 μl, more preferably from 15 μl to 30 μl. It consists of highly porous spherical particles with a diameter of , optimally about 20μλ). these The spherical particles have a pore volume of 25-65%, more preferably greater than 40%. do. According to the ultrastructure of the present invention, individual bone cells and bone cell layers are specialized trabeculae. stimulates the formation of Furthermore, the bone substitute material of the present invention also stimulates individual bone cells. be done. This results in very rapid bone ingrowth in this alternative material. let A rigidly fixed sphere of size 15μI to 50μ sides, especially 20μR. The spherical or spherical part is the surface of the optimal structure (quaternary (See Figure 1). The diameter of the spherical particles is preferably is about 20 μπ, which is the same size as a bone cell.

The pores of highly porous fillers can be filled with absorbable and compatible substances . This substance is preferably the binder used. As a special example of a binder polypeptide, polylactate, polyglycolate or their co-precipitates, There are latin, collagen and calcium compounds. The filler preferably binds Harder than the agent.

Organic matrices form bone cell layers much more rapidly than metal or ceramic surfaces. It turns out that it can be done. Ceramic surfaces are better for growth than metal surfaces I understand. However, the surface of sintered apatite is even more Subject to more rapid cell proliferation. The collagen matrix is also a pure ceramic surface. It was found that cells proliferate (distribute) more rapidly than on pure apatite surfaces. Ta. The optimal growth rate is that the organic matrix (e.g. collagen) is This is achieved when including. This coating has a quaternary structure ( superstructure).

The coating of the present invention is fully absorbable. Completely absorbable matrix is absorbable It has great advantages compared to its parent body. This covering should be It is always rapidly absorbed and replaced by bone. The closed remains cell layer is a dense tertiary sphere. In a very short time from the assortment (see Figure 2) and the thin collagen coating that remains on the sphere. You can get it at This layer of bone cells forms a layered bone that can withstand heavy loads. can. The density of the assortment of spheres, its specific size, and the first arrangement of osteoblasts. Columns have a special structure. For this reason, rearrangement of cells and trabeculae that form is unnecessary. be. As a result, resorption and new bone formation (remodeling) steps are not necessary.

In one embodiment of the bone substitute material, some of the filler of the dressing is in the form of fibers.

The monofilamentous filler preferably has a diameter of between 100 μm and 300 μm, preferably about It consists of fibers of different lengths with a thickness of 200 μm. This fiber preferably has 2 between ii and 15xz, more preferably at least 3 mm and at most ]Oxx , the most suitable length is between 4 and 5R11. The monofilament filler is carbon, collagen, polypeptide, polyacetate, polyglycolate or The coprecipitate and gelatin may also consist of a substance such as guttate. single The proportion of fibrous filler is between about 5% and 15%, preferably about 10%. be. In a preferred embodiment of this embodiment, the fibrous filler is a matrix-free and dense filler. Part of the network. The network structure consists of a chain of beads. and the diameter of the beads is between 15 μm and 50 μm, preferably about 20 μm. . The beads are so closely packed that they touch each other in a three-dimensional structure.

The network can be arranged as a stocking, especially as a multilayer stocking. Ru.

The production of the bone substitute material of the present invention uses collagen as an example of a fully absorbable binder. will be explained below using Using conventional methods, large amounts of collagen are extracted from animal bones. Manufactured from. Collagen, like glue, is composed of spherical apatite or TCP. (In the present invention, the expression "apatite" preferably refers to "hydroxyl rTcPJ means "tricalcium phosphate". ). of the sphere Dense assortments are produced using ultrasound, vibrators and/or other agitators . The supporting frame of the basic body is then filled with this coating. Thus, the present invention A structure in which a tertiary structure and a quaternary structure are combined is obtained. This structure is a preferred embodiment of the present invention. This shows one of the preferred bone substitute materials.

A tertiary bone substitute material combined with a quaternary superstructure can also be obtained by the following method. can. A ball with an optimal size between 200μ shoulder and 3000μ shoulder is made of apatite or T It is made from multiple collagens mentioned above including C'P. These spheres then absorb Lay on the possible thread and form a chain of beads. This chain is circular They are made into continuous stockings using a knitting machine. A network of chains of beads forms be done. Implants of various types, for example for the treatment of bone defects, can be It can be manufactured by bending the chain structure inward and pointing outward.

The mechanical stability of the bone substitute material of the present invention is determined by the ability of threads, fibers, and thread networks of various lengths. Alternatively, it can be significantly improved by bonding steel to the matrix (see Figure 3). child Bone replacement materials such as Bone Replacement Materials are also a preferred embodiment.

Particularly preferred embodiments are filled with knitted stockings or networks of one or more layers. It is used as a filler. It is then filled with a binding substance. Do it like this Also preferred is a thin plate of the fixation part of the prosthesis obtained by. Thin plates have very significant mechanical shows resistance (see Figure 4).

Bone production is particularly effective when the stocking takes the form of a bead chain. It can stimulate.

Such bead chains are made by adding small apatite stones to the fibers as they are extruded. obtained by mixing spheres (15 μm to 30 μm, preferably 20 μm) of be able to. Such embodiments are also preferred. Multi-layered, three-dimensional bead chain The structure can also be used instead of the single layer bead chain according to FIG.

FIG. 6 shows a bone fixing nail for fixing a bone screw made from the bone substitute material of the present invention. An example of 10 is shown below. This bone fitting nail lO has five rings or bulges 12, It consists of a hemispherical tip 14 and a cylindrical end 16. The spherical basic body 18 is A base material structure consisting of a sphere wrapped in a network 19 is formed. After being attached to the bone, The dowel 10 encases and/or strengthens the bone. Dowel nails are It sits securely within the surrounding bone and provides long-term tension when inserted. We can provide screws that will fit your needs. Fixation to the bone is achieved by expanding dowels or This can be accomplished by spreading out the dowel by tightening it inside the screw. Match The nail may have multiple vertical or horizontal grooves to aid insertion into the bone. stomach. Alternatively, from a double-walled stocking basket, corresponding to the dowels shown in Figure 6, It may consist of The bead chains are held in this basket and connected to each other. to form a support frame when the car rotates.

FIG. 7 shows a bone marrow cavity closure (20) made from the bone substitute material of the present invention.

The obturator 20 has a head 22, a conical plug 24 and a plug over the remainder of the marrow cavity. The conical ring 26 is inserted by rotating the screw 28. . The ring 26 then flares out and forms the honeycomb of the bone canal shown diagrammatically in FIG. Firmly engages the interior of the structure. Made from the bone substitute material of the present invention and expands within the bone Closing materials in the form of simple cylinders or large thin plate cylinders or screws treat bone gaps It is a suitable means of filling the hole in the ethmoid bone. Closure material is inserted into the remaining canal by bone screws and then the screws are removed. Such closure materials may be used to close bone canals and/or bone creates an airtight seal against the internal pressure of the medullary canal, prevents secondary bleeding and hematoma formation, and and promote bone healing.

For all shapes: Gap-filling Subonno≦ (see Figure 8) has a bead chain structure. It can be manufactured by bending inward and facing outward. This sponge uses the well-known "polishing" It is in the shape of a "ki pad". The sponge fills the gap between bones by expanding its belly button. can be easily fixed. Spread the sponge using a cone-shaped or nail-shaped stopper. can be done.

Figures 8b and 8c are perspective views of a three-dimensional bead chain network; FIG. Bone substitute materials are also used in prosthetics. Can be placed on a bottle or stem.

The covering shrinks as it dries over the fixed part of the prosthesis, thus reducing the support frame. Intimate contact occurs between the matrix, the matrix coating, the filler and the base material. like this The prosthesis coated with can be inserted into With a suitable support material, a closed osteogenic layer is formed on the surface.

This layer can provide a stable anterior support for the prosthesis component. significant support The trabeculae are formed and then a matrix coating is applied to the trabeculae. Next, the bone It can grow deeply into the surface structure of the foundation object (supporting frame).

FIG. 9 shows the fixation part of the prosthesis of the invention to which the material of the invention is applied. this The material consists of a bead chain structure. Figure 9b shows the basic material and the 3D structure. Figure 3 shows a schematic cross-section of the layers. Figure 9c shows a view of the top layer of this structure.

The tertiary structure may be part of a prosthesis or part of a covering.

If the resorbable covering consists of tertiary and quaternary forming elements, a metallic prosthesis The stem has supporting ribs or allows bone ingrowth and bone support. Must have continuous pores.

For example, due to the inducing effect of small apatite particles coated with collagen, bone growth is stimulated. Bone ingrowth and bone ingrowth can be normal or uncovered in implants. It is even more rapid compared to Imbrandt.

In a particular embodiment of the invention, the bone substitute material itself is a whole implant or Constitutes the fixed part of the prosthesis. This material assumes the appropriate shape during manufacture. support The basic body in the frame is a three-dimensional structure that is strongly supported by external or internal supports. It can be a network.

The simplest form of an implant would be a sintered sphere.

Such an assortment of spheres can also be achieved by external binding (holding basket). Ru. In addition, bead chains can be shaped like supporting ribs or “tires.” Either by a skeleton that absorbs internal pressure or by individual melts with adjustable elasticity. Processed and supported by hardening with contacts. bone substitute material The elasticity of a section is determined by the number and density of welds that firmly connect the beads to each other. can.

Figure 1O shows that the network is extensive and has no necessary stiffening or support. This indicates a fixed part that is also a fixed part. For example, for instructional purposes or for surgical purposes. Artificial bones for humans can also be advantageously produced from the bone substitute material of the present invention.

The three-dimensional network consists of implants with different elasticities (e.g. different cross-sections of the runt) or interwoven to produce Book The bone substitute material of the invention can be used as a covering, a canopy, a cylinder, a flat coil spring, a ball or a spong. It can take the form of ji.

Induced bone formation is achieved by adding chemically active substances to the parent material. It can be further promoted. Chemotactically active substances from bone matrix and necrotic bone are known. For example, it contains "bone morphogenetic protein" and has a particularly large inducing effect on bone formation. effect. Preferably, such a mixture is added.

The induced bone formation is caused by highly porous spherical particles used as fillers surrounding It has been shown that this is particularly preferred when the material is harder than the parent material. This is what this means. allow these particles to exert a mechanical stimulation effect on the remains cells. such implementation Examples are also preferred.

Another advantage of the bone substitute material of the present invention is that it contains a significant amount of binding agent. this The material should have a large capacity with good release rates for the mixture of active substances. I understand.

Implants, which lack blood vessels and are not protected by the body's self-defense mechanisms, are easily colonized by bacteria. It is known to be dangerous. This means that antibiotics may not be used in bone substitute materials. This can be prevented by adding Many studies have shown that bone cement It has been carried out on several antibiotic mixtures. To date, cement-free prostheses does not have this protection. However, bone substitute materials made of resorbable substances are All types of cement-free plastics with effective preventive protection against infectious diseases. It makes it possible to provide rotese and implant.

Local application of other drugs, such as hemostatic agents, is known from external treatments. the By mixing such substances with the bone substitute material of the present invention, such substances can also be It can also affect organs that cannot be accessed by treating the body. The hemostatic agent in the binder is in the bone bed Adjust bleeding immediately.

Vasoactive substances such as noradrenaline and its derivatives also cause vasoconstriction due to their vasoconstriction. Helps control bleeding. In this way, blood penetration into the interface can be prevented and the mechanical strength of the interface degree can be maintained for a longer period of time. As already mentioned, bone-inducing and chemotactic can be mixed with active substances and binders. These substances make new bone formation more rapid. cause it to occur quickly. The use of hormones, along with substances like calcitonin, can be used locally have an effect. These prevent newly formed bone from being resorbed.

The following examples serve to clarify the invention.

Example 1 A three-dimensional support framework, that is, a basic body that touches each other and surrounds a demarcated space. Bone substitute materials (including those with and without coverings) are as follows: can be manufactured. Absorbable organic matrices such as polyglycolates and polylactates Polypeptides, which are substances, are made by mixing various additives such as softeners until they are melted. heated in the extruder. Filler particles (highly porous tricalcium phosphate spheres) ) is then added and the whole is heated and stirred vigorously. tricalcium phosphate The spheres are preferably made of highly porous sintered tricalcium phosphate (mostly (exhibiting beta structure) is obtained by grinding in a ball mill.

In this way, the melt produces a homogeneous filler distribution upon stirring. Apply pressure The material in the melt is extruded through a narrow nozzle, and in a settling tank, it is It becomes a thick fiber. Spherical or spherical structures on fibers can be obtained in various ways . Spheres with large diameters (e.g. from tooooμl to 3000μm) are pure can be drawn mechanically into a thread, or directly at the opening of the nozzle, which can be varied infinitely. The diameter can be changed by vibration. The latter method is particularly suitable for small direct lines of about 500 μm order. More preferred for spheres with a diameter of

In this way, a continuous bead chain with adjusted bead size is created. , can be produced by settling the melt in a tank.

A small sphere of filler with a diameter of about 15 μm to 30 μm is probably surrounded by the matrix material. , this bead chain can be attached to the outside.

The beaded chain produced in this way is then, for example, a Weissenburg Continuous circular knitting manufactured by Müller and Doubeet of Neuenburg On a machine, it can be knitted to form a continuous stocking. stockings Rotate inward several times and you'll see a very dense three-dimensional network of bead chains. can. Its outer shape resembles that of a tire. This network ideally It is occluded within the bone cavity by a central expander.

Example 2 A network of layered corpuscles allows for outward rotation of such a network. It can also be formed by This means that metal bead chains can be woven into networks. or weld them and turn them outward (- to make several layers and make them harder by welding) This is made possible by This means that you can set different elasticities on the whole implant. and make it possible. One very simple way is to create such a network as a core ball. The core is completely surrounded, like a stocking, by rotating . For example, after rotating the stocking 1'80°, the second layer can be rotated.

This process allows this continuous bead chain stocking to form multiple layers. It can be repeated until.

The second method is to create a layered network of corpuscles according to a precisely calculated f = plan. The process involves welding and hardening the sets. Further curing results in filler grains exhibiting a quaternary structure. Whether or not it contains offspring, the cavity is filled with organic parent material. Matrix and filling The characteristics of the agent particles are that they are absorbable and can be coated with materials.

Example 3 The stem of a complete prosthesis consisting only of a network of layered bodies: Individual or layered networks of constant parts can be produced in a variety of ways. 2. Kidney Fixation parts containing a network of corpuscles can be prepared at reasonable cost using conventional methods. It can be produced in The production of tertiary structures is based on the method of casting into lost shapes. This shape is , can be produced using a layered network of wax spheres as a meltable mold. this Their method is known from dentistry and all simple on cast metal shafts. Based on a unique surface structuring method. The support framework thus obtained is then used to fill the cavity. If used for this purpose, it is coated with an organic matrix. The coating material is preferably filled with It contains filler particles and exhibits all the features of quaternary structure described above. The coating transforms the tertiary structure into a quaternary structure. This can be done by immersing the structure in the melt.

Example 4 There are also bone substitute materials that consist of a three-dimensional support frame with a tertiary structure of the basic body and do not have a covering. , can be used as a starting material for artificial bones. First of all, the fundamental field is, for example, plus Pour into the casting mixture consisting of ticks and completely surround. Next, the basic body is It is removed from the casting mixture leaving only the tubular structure of the casting mixture. In this case, the base The body consists of a substance that is chemically soluble in a solvent that does not affect the casting mixture, or In this case, the basic body is physically (eg, electrostatically) removed from the casting mixture.

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INTERNATIONAL APPLICAT ON No, PCT/EP 85100711 (SA 11760)C! (-A-6117942910 6/79 None+J-A-001180911106/80 DE-A, C 28SO5E16 2910S/80DE-A-291703717104/E IONoneCH-A-64373229106/[14None

Claims (35)

[Claims] (1) A three-dimensional support structure of a basic body that touches each other and surrounds a partitioned space, Absorbable fillers and absorbable binding substances based on strong calcium compounds (matrix ) and a covering consisting of a bone substitute material. (2) The supporting structure is made of absorbable organic material with a thickness of 50 to 300 μm including the basic body. and/or non-absorbable fibers with a thickness of 100 to 750 μm. or wire, and/or the three-dimensional maximum of a basic body of a predetermined size. Bone allowance according to claim 1, characterized in that it consists of a high-density assortment. Replacement material. (3) The basic substance is tricalcium phosphate, apatite, collagen, polypeptide and absorbable substances, such as mixtures of two or more of these substances, and/or , titanium, tantalum, cobalt, chromium, molybdenum, one of these metals metal, such as an alloy, and/or a special steel. Bone substitute material according to item 1 or 2. (4) Claim 1, characterized in that the basic body is a sphere or a spherical object. The bone substitute material according to any one of Item 3 above. (5) A claim characterized in that the size of the sphere is between 200 μm and 3000 μm. Bone substitute material as described in Scope 4. (6) Claim 4 or 5, characterized in that the spheres have different diameters. Bone substitute materials listed in Section. (7) Spheres with diameters between 200 μm and 1000 μm (average 500 μm) and 800 μm and a sphere of diameter between m and 3000 μm (average 1000 μm). A bone substitute material according to claim 6. (8) Some or all of the basic bodies are in solid three-dimensional contact with each other. A bone substitute material according to any one of claims 1 to 7. (9) Individual or layered basic bodies are rigidly supported by internal or external supports. Claims characterized by forming a three-dimensional framework or network The bone substitute material described in any of Items 1 to 8. (10) The three-dimensional network is twisted, interwoven, or reinforced. The bone substitute material according to claim 9, characterized by: (11) A three-dimensional network can be used to develop tension resistance due to internal pressure using the tire method. characterized by being supported like an enclosure or like a framework by internal girders. A bone substitute material according to claim 9 or 10. (12) Claim 1, characterized in that the surface of the basic body has a fine structure. The bone substitute material according to any one of Items 1 to 12. (13) The microstructure takes the form of spheres or spherical sections with diameters between 15 μm and 30 μm. 13. The bone substitute material according to claim 12, characterized in that: (14) The covering fills the space between the basic bodies of the support structure or Claims 1 to 13 characterized in that it covers a surface. Bone substitute material. (15) The filling of the coating is between 10 μm and 200 μm, preferably 15 μm and 30 μm in diameter, with a pore volume of 25%. Any of claims 1 to 14, characterized in that it is between 65% and 65%. A bone substitute material described in (16) highly porous tricalcium phosphate or hydroxyl apatite particles or Particles of related calcium compounds are used as fillers and their pores are absorbable. and compatible substances as described in claim 15. Bone substitute material. (17) The absorbable and compatible substance is the binding substance (base) of the covering. The bone substitute material according to claim 16, characterized in that: (18) Polypeptide, polylactate, polyglycolate or co-precipitation thereof substances, gelatin, collagen or calcium compounds are absorbable and compatible. Claims 16 and 7, characterized in that they are used as substances or binding substances or the bone substitute material described in item 17. (19) From claim 15, wherein the filler is harder than the binding material. Bone substitute material according to any of items up to item 18. (20) Claim 15, characterized in that the diameter of the filling is approximately 20 μm. The bone substitute material according to any one of items 1 to 19. (21) A claim characterized in that a part of the filling of the coating takes a fibrous form. Bone substitute material according to any of Items 15 to 20. (22) The single fibrous filler is a fiber whose length varies from 2 mm to 15 mm. The bone substitute material according to claim 21, characterized in that it consists of: (23) The thickness of the fiber is between 100 μm and 300 μm, preferably 200 μm. The bone substitute material according to claim 22, characterized in that: (24) Single fibrous fillers include carbon, collagen, peptides, polylactate, and polypeptide. polyglycolate or their co-precipitates, gelatin or gut? According to any one of claims 21 to 23, characterized in that: bone substitute material. (25) Claim No. 1 characterized in that the filling forms a closed network. The bone substitute material according to any one of Items 21 to 24. (26) The spheres of the network of sphere chains have a diameter between 15 μm and 50 μm. However, the balls are packed so tightly that they touch and form a three-dimensional frame. Claims 1 to 25 characterized in that Bone substitute material. (27) Claim 26, characterized in that the diameter of the sphere is approximately 20 μm. Bone substitute material. (28) Claims 25 to 25 characterized in that the network is multi-layered. The bone substitute material described in any of items up to item 27. (29) The mother is a hemostatic agent, an osteoblastic substance, an antibiotic, a vasoactive substance, and an osteoactive substance. Claims 1 to 28 characterized in that they contain a mixture of hormones. A bone substitute material as described in any of the above. (30) Contains antibiotics (e.g. gentamicin) effective in treating bone infections The bone substitute material according to claim 27, characterized in that: (31) Noradrenaline and/or its derivatives as a vasoactive substance The bone substitute material according to claim 29, characterized in that it comprises: (32) Claims characterized by containing calcytosine as a bone active hormone Bone substitute material according to paragraph 29. (33) Taking the form of a socket, cylinder, flat coil spring, ball or sponge The bone substitute according to any one of claims 1 to 32, characterized in that material. (34) Treatment of all prostheses, joint prosthesis fixation parts, bone coverage, and bone gaps. Joint implants or joint replacements for fixing bone screws or cutting Claims 1 to 3 as a bone fixing nail for closing a bone marrow cavity in the case of Methods for using bone substitute materials according to any of paragraphs up to 3. (35) A casting mixture is used instead of the coating, and this casting mixture covers the basic body. from a substance or casting mixture whose basic body dissolves in a medium that does not affect the casting mixture. Claims 1 to 32 as an artificial bone made of physically removable material How to use bone substitute materials according to any of the up to.