DE19654884C2 - Molded body - Google Patents

Description

The invention relates to a shaped body, which as a shaped, Support and growth substrate serves, comprising an Ab covering membrane for tissue regeneration and / or knot Chen regeneration and its use.

The molded body according to the invention, which as a molded, Support and growth substrate is used at the stand not a role model for technology. In the state of the art very much however, various covering membranes are well known.

In bone surgery, for example in the recon structure of bones in plastic surgery or  in jaw surgery, it is common Bone defects in the form of recesses or height lungs in the body's own bone tissue with bone on fill building material, which usually consists of a Mixture of bone substitute material such as hydroxyapatite granules, and the body's own bone particles. To ensure that the bone building material in the essentially only from the bone side through bones, but not in undesirable Way of epithelium and subepithelial connective tissue closed the recess with a cover membrane. Only if a completely bony one Growing of the bone building material guaranteed the bone defect site can be essentially remove.

In the prior art, cover membranes are, for example described from polytetrafluoroethylene films, each but have the disadvantage that after the Bone defects remain in the body and thereby may give rise to complications.

With the development of bioresorbable polyester foils lien, such as B. described in WO 92/15340 A1, the Provided that during or after loading side of the bone defect by waxing in own bone tissue the previously required Ab Cover membrane no longer available due to absorption was.  

A major disadvantage of such polyester films is however, in their high stiffness and brittleness lack of addition of plasticizers. These properties have the consequence that Herge from such material made covering membranes difficult for the three-dimensional nal trained bone defects are to be adapted. In addition, it persists until the time of absorption the latent danger that the very thin, over the mem Bran lying soft tissue (mucosa) is injured.

Stiffness and brittleness can be reduced by using Eliminate the set of plasticizers as far as possible, but is the use of appropriate plasticizers itself not unproblematic with a view to that through they may cause foreign body reactions, such as e.g. B. nerve irritation or allergic reactions. Another disadvantage of using Plasticizers can currently be seen in the fact that the results Clinical trials of relevant substances zen only on a very small number of conducted tests with an equally small number of different plasticizers.

Another disadvantage of polyesters Cover membranes are in their low mechanical loading resilience to see. Even with low mechanical Such membranes become stressed in the bones defective pushed in with the result that only a part the bone defect is filled with bone.  

WO 92/10218 A1 describes a polymer material for cover membranes, the glass transition temperature near the Kör temperature. As a result, the membrane is in situ flexible and the adaptation of such Ab Cover membrane on a bone defect can easily be machined be made. This does indeed solve the problem solved flexibility of the polyester material, not however, that of poor mechanical stability.

Another aspect to consider when designing Ab cover membranes to consider is the biocom compatibility of cover membranes that differ in their Be wettability, the extent of cell ingrowth so like the rate of cell growth in the Expresses membrane surface. With synthetic membra NEN is typically attempted that the material in inherent low biocompatibility due to a corresponding appropriate surface design to compensate for what ever but both with a view to the resulting he result and the associated costs unsatisfied is prevailing.

In contrast to synthetic membranes, cover Membranes based on collagen have a clearly different improved biocompatibility. In addition, egg ne collagen membrane when wet by 20 to 50 be stretched, which allows the diaphragm to go over three diodes to tension dimensionally complicated bone defects.  

However, it is precisely this extensibility that such Covering membranes even less to accommodate mechanical ones Forces are more suitable than the synthetic membranes. Accordingly, a cover membrane on Col Bone defect covered by the layer practically full constantly with augmentation material or bone replacement material be filled up. Especially with larger knots The use of augmentation mate can cause defects rial or bone replacement material due to the need Maneuverability of the stable anchoring and a through penetration of the material mentioned by the body's own Bone material will be difficult.

As stated at the beginning, the intention is to use it to see a covering membrane in that the Kno Chenaufbaumaterial essentially exclusively from the bone side grows through. This assumes that for the entire cover to be dismantled comparable degradation kinetics prevail, or but not this by attaching the cover membrane changed in an uncontrolled manner. Will ever but a collagen membrane over a bone defect spans, thinning occurs at specific points of the membrane leading to an accelerated breakdown kin tic and ultimately lead to the bone defect not exclusively bones from the bone side will grow through.

DE 43 02 709 C1 relates to a covering device for temporarily covering one with bone augmentation tissue  rial, such as hydroxyapatite granules, filled recess in the body's own bone tissue with a covering membrane, wherein the covering membrane assigned a stiffening layer is not.

DE 43 02 708 A1 also describes a covering membrane for temporarily covering one with bone structure material, such as hydroxyapatite granules, filled recess tion in the body's own bone tissue, the covering membrane consists of resorbable membrane material.

DE 44 14 675 C1 describes a covering device for temporarily covering one with bone building material al. such as hydroxyapatite granules, filled bone end fektstelle, in particular recess, in the body's own Bone tissue, with the defect site in the main perforated reinforcement covering form-stable tion element made of relatively stiff, but bending same material, such as metal support grids or the same, and one ge through the stiffening element worn single or multi-layer covering membrane, whereby at least one of the layers of the cover membrane as Lö medium film on the application-specifically shaped Stiffening element is applied.

DE 195 20 867 A1, published December 12, 1996, be meets a cover membrane made of body-compatible, possibly also from at least partially absorbable mem branch material for temporarily covering one with Bone building material, especially hydroxylapatite gray  nulate, filled recess in the body's own tissue, the soft tissue and / or the bone tissue be facing side of the cover membrane (each) Reten tion support facility to improve Re tention of the soft tissue or the (respective) colla gene structure (s) on the covering membrane sen.

EP 0 637 452 A1 describes a material for medicine use, which consists of two layers of a colla Genmembran exists that by means of an adhesive are attached to each other, and a grid-like intermediate Has interposed material, the average pore size of the intermediate material between 100 and is 2000 microns.

Patent Abstract of Japan from September 12, 1995 / JP 07236688 A, relates to a layer material made of bioabsorbent plastic and collagen, being a three-layer Structure is provided that consists of a collagen sponge layer, a coating layer of polylactic acid and there is another layer of collagen sponge, the Hy contains droxylapatite granules.

WO 90/13302 describes a composition for the ge controlled tissue regeneration which is a biodegradation bare, bioactive membrane comprising a first and has second side, the first side of the mem bran one or more biologically active substances  points, which does not exist on said second page they are.

DE 195 20 866 A1, published December 12, 1996, be hits a device for treating one in verbin area of the two legs of a tooth bifurcation formed bone recess, with one, a cell occlusion active covering membrane with flat Ab covering device for temporarily covering the kno Chen recess in relation to the surrounding soft tissue, which after passing between the legs of the Bifurcation towards the distal end of the tooth bendable and after connecting to the two for connection line of the longitudinal central axes of the two legs in the we substantial parallel tooth surfaces in the border area between dental cement and enamel can be attached to the tooth is, the cover on both of them Border area between dental cement and enamel speaking distal transverse edges a fixing aid has, the fixing aid a fastening device for positive and / or non-positive Festle has the covering membrane on the tooth.

The invention has for its object a form provide body that is particularly well biocompatible and, especially with large bone defects, a high one has mechanical stability, and uses the same.  

According to the invention, the object is achieved by a molded article per, which serves as a form, support and growth substrate, solved according to claim 1.

Furthermore, the problem is solved by the use gene according to claims 35 and 36.

Further embodiments result from the subordinate sayings.  

The following are special designs and We kungen of the molded body with covering mask bran mentioned.

The invention is based on the surprising finding reasons that the molded body according to the invention forming covering membrane for tissue regeneration and / or bone regeneration that is at least three Has layers, the two each outer Layers consist of a naturally occurring material and at least one intermediate layer of minde there is at least one plastic material, a biodegra representable or bioresorbable membrane which a particularly good degradation and resorption kin tics and in addition to their high mechanical stability lity in an excellent way that for the tissue rain regeneration and / or bone regeneration required Barrier function ensures that without it there by affecting the rigidity of the Barrier function ensuring layer comes In addition, an adaptation of the cover membrane to the due to the geometry of the bone defect to be repaired given form allowed.

Among naturally occurring material, also here as natural material are referred to in this Zu also derivatized forms and mixtures understood the same.  

The membrane forming the shaped body according to the invention bran can handle small and medium-sized bone defects Maintain barrier function for at least 6 months ten and then within a period of 9 to 12 months from Body or organism without clinical complications are metabolized. For large-volume bone defects the barrier function is at least 9 months, and the membrane can be in a period of 15 to 18 months of the body or organism without clinical complications ions are metabolized.

Due to the high biomechanical stability of the the covering membrane forming the shaped body is not Bone replacement material needed for support like this is required for mechanically unstable membranes, to prevent collapse in the bone defect.

The fact that the two outer layers consist of a naturally occurring material, one results quick and easy integration of the soft partially woven into the membrane surface of the covering membrane, which is an important biological and clinical prerequisite is to avoid the dehiscences of the membrane.

The use of plastic material that is biological degradable is not only due to its metabolizability the covering membrane forming the molded body, but is also of importance insofar as an Un depending on the availability of suitable biological material is guaranteed, beyond that  may show batch-dependent differences can which the properties of the cover membrane in not can change predictably.

The use of plastic material, and especially egg thermoplastic, also offers a special ren advantage over z. B. made from collagen Membranes as it is in the adaptation of the molded body training covering membrane to three-dimensional archi tectonically complicated bone defects do not become one Thinning of the rele for the function of the covering membrane vanten layer (s) as a result of the adaptation process which then accelerates to an uncontrolled rate would require building kinetics.

Especially the use of poly (D, L-lactide) or Po ly (L-lactid-co-D, L-lactid) as plastic material ver borrows the covering membrane forming the molded body unique degradation and resorption kinetics, as they are using the currently available biode not guarantee gradable natural materials is, with a weight ratio of L-lactide to D, L-lactide of 40:60, 50:50, 70:30 or 80: 20 with a view of the degradation and resorp tion kinetics is particularly advantageous.

The consisting of a plastic material, between the two outer be made of a naturally occurring material standing layers can be a zel have a occlusive porous structure. For the bones  regeneration it is very important that a class re separation between those on the tissue and / or knot tissue regeneration involved becomes. It can be advantageous that the celloc inclusive structure is porous. This is particularly useful Things start when due to the growth charac Cell characteristics, for example, a rough upper area is required and this, for example, as an setpoint for growing cells. Vice it can also be beneficial if the celloc inclusive layer has a non-porous structure, especially if that's between the two outer consisting of a naturally occurring material Layered layer of cells does not exist delt, but is required as a barrier to for example, contact inhibition of cell growth effect and thus to a defined tissue structure to get.

The use of collagen in the molding forming cover membrane is with a number of advantages len connected, which can both result from that at least one of the two outer from a natural Lich existing material layers Has collagen as well as the fact that at least one the two outer be made of a natural material standing layers of collagen.

The use of collagen in particular speaks for itself high biocompatibility and generally given  Biodegradability of this material. Because the stability as well as the barrier required for a covering membrane refunction essentially from that between the two outer consisting of a naturally occurring material Layers of layers of at least one art material with the collagen associated disadvantages regarding the stability of the Materials and thinning in places with high tension compared to the excellent biodegradability be accepted and lend as a whole the covering membrane according to the invention their unique egg properties.  

The fact that at least one of the two outer from a natural Lich existing material consisting of layers of collagen stands, the wetting and ingrowth of cells and finally the speed of the soft tissue weave growth in the membrane surface improved, see with the conditions when using excl Lich synthetic polymers or Ab built up from them cover membranes.

The advantages mentioned above apply particularly when if the collagen is type I and / or IV.

The collagen provides the cells and the tissue with an optimum le surface for colonization and waxing available. Furthermore, the collagen is due to the cells Natural origin compounds for biochemical Processes and bonds available. This will for example in the case of bone defect regeneration ten, which is essential for successful bone regeneration tig necessary blood coagulum bound and on site, d. H. at the Bone defect, held. This enables the soft tissue side  Collagen a rapid growth of the tissue of the mucosa, so that the covering membrane in the soft in a short period of time partial tissue is integrated without complications.

The outer layers consisting of collagen can ent neither be porous or fibrous or one layer one porous or fibrous and the other a smooth structure exhibit. If the side of the bone defect facing the Covering membrane has a porous or fibrous structure, are the be in terms of ingrowth behavior particularly advantageous surfaces. Conversely guaranteed the smooth structure of the second outer layer that its Settlement by both wanted and unwanted tissues barking largely absent or controllable is delayed. Furthermore, you have the Possibility to continue the resorption kinetics influence, and not just that of the outer one naturally occurring material existing layer (s) but also the intermediate one consisting of plastic material Layer. In this way, by a surface Chen modification further influence on the resorp tion kinetics of the barrier function ver middle layer made of plastic material ge be taken.

Conversely, through a fibrous or porous structure the two outer ones made of natural material, and special Collagen, existing layers are ensured that for both sides of the membrane the cell opening growth and thus the uncomplicated integration of Cover membrane created necessary conditions  become. Such a configuration can then be particularly useful be of advantage if the bone defect to be repaired ver is equally small and the speed and the The amount of cell growth is approximately the same on both sides is, so that a targeted slowdown in cell growth on one side of the membrane, typically that of the Soft tissue, by offering one for cell wax tum less suitable surface, for example in the form a smooth surface structure, is not required.

A collagen edge of the cover membrane allows for the absorption a certain part of the mechanical forces involved in the Adaptation of the covering membrane to the tissue to be repaired or bone defect occur due to the polymer matrix reinforcement. In addition, such a colla allows genrand, which can be 5 to 10 mm, that the Ab cover membrane is adapted close to the bone. As a result the phenomenon of thinning does not occur as it does for Collagen membranes are observed.

Has at least one of the covering membranes Laying up a bone substitute material is guaranteed The regeneration of bones is significantly faster expires and the corresponding known in the art Bone replacement materials as a starting point for further chondroblastic and osteoblastic activities to serve.

Basically, bone substitute material can be used in any Layer of the cover membrane are introduced, taking it out obvious reasons is particularly advantageous, the Kno  Chen substitute material in one of the two outer from a natural ch existing material to incorporate existing layers, and preferably in those facing the bone defect, and / or possibly another, between the outer end of the bone made of a naturally occurring material the layer on the one hand and that between the two outer ones layers consisting of a naturally occurring material layer of at least one plastic material on the other hand, assigned layers.

In addition to the installation of bone substitute material, the In incorporation of at least one biologically active agent the possibility of using a regeneration process Influence a variety of biological processes.

Basically, a corresponding biologically effective Agens practically everyone who builds the covering membrane Layer and the elements or structure contained therein doors, e.g. B. the bone substitute, who added the.

There are special advantages if the between the two outer ones made of a naturally occurring material Layers of layers have a content of min least has a biologically active agent.

As biologically active agents, growth can factors, antibiotics, pain relieving agents, agents cien that affect cell division and vascularization flow, coagulating and anti-coagulating agents, immunosuppressive and immunostimulating agents, cyto  kine, chemical attractant, enzymes and combinations there of serve.

The effectiveness and especially the mechanisms of action of be said agents are known to the person skilled in the art. So z. B. Growth factors serve to generalize cells and possibly to stimulate special cell populations for increased growth conditions to the existing tissue or bone defect fill up as quickly as possible. The use of antibiotics is particularly indicated if it is large or is difficult to clean tissue defects or the environment in which the covering membrane is inserted, has a high germ load. Agents that the cell Allow division and influence vascularization in addition, a rapid regeneration of the tissue or Bone defect. Depending on the blood flow ver The addition of coagulating as well as of anti-coagulating agents. The Ver Use of immunosuppressive agents is special then displayed when e.g. B. due to allergic reaction otherwise worsen the healing process would come. Conversely, immunostimulating agents be advantageous if it is desired in the field of Cover membrane to generate an enhanced immune response. Cytokines and chemical attractants can Mechanism of action the immigration of different cell populations represent a possibility, the healing process continue to steer or force. The addition of Enzymes allow a further modification of the rain generation process and can affect both the material the covering membrane as well as on the regenerated or itself  regenerating tissue.

With the agents mentioned, it is also possible in principle Lich, both within the layers and over the Layer cross-section and / or layer longitudinal section Gra served to realize the respective requirements to correspond to tissue regeneration.

Additional advantages of the covering membrane particularly related Lich their stability results from the fact that at least one of the two outer ones consist of a naturally occurring material de Layer a polymer matrix from plastic material sums up. This polymer matrix can be made of plastic material be built, similar to that in the between the two outer ones made of a naturally occurring material Containing layers of plastic material is. The benefits mentioned there regarding degradation Availability and deformability also apply here analogously.

Due to the porous structure of the polymer matrix, an grow cells that contain the polymer matrix de (n) layer (s) of the covering membrane possible. Consequently can the natural material through the ingrown tissue to be resorbed or replaced and, depending on the selection of the polymer matrix material or its dimensions ionization, the absorption kinetics of which are controlled, with the result that the polymer matrix in the rain tissue is transferred and this additional Sta imparts til it finally resor beers.  

Although it makes sense to use the poly mermatrix in several of the layers of the invention It is particularly important to integrate the cover membrane partial to integrate them into those layers that are between the tissue to be regenerated and / or bone and that between the two outer ones from a naturally occurring one Material existing layers are lying layer especially in this area, especially for large Bone defects require mechanical stability guarantee.

Due to the three-dimensional deformability of the covering membrane bran will be an optimal adjustment to the one to be fixed Tissue and / or bone defect guaranteed, especially in Connection with the collagen margin already mentioned. The thermal deformability is essentially due to the Material properties of the plastic material influenced and allows fine modeling of the cover membrane if necessary, after it is already in place without large mechanical forces would have to be applied, resulting in a particularly gentle and reliable application of Cover membrane leads.

As can already be seen from what has been said, this is an option especially the in vivo use of the invention Cover membrane. Beyond that there is the possibility ability to use such covering membranes in vitro, for example, when it comes to complex three-dimensional generate tissue or organ structures that may be transplanted.  

A basic application is also ex vivo. B. possible in heart-lung or dialysis machines. Here fulfill existing equipment Tissue or organ parts that the the invention Molded cover membrane as growth and Use shaping substrate, functions that nor sometimes taken over by the body's own structures the.

Basically, the molded articles according to the invention can be used for a variety of applications so z. B. for the regeneration of tissue and / or bone end fect. The following is an example of the benefits received a shaped body, which the elimination of Serves bone defects. However, it is for the skilled person obvious that corresponding configurations of the Shaped body according to the invention also for the elimination of their defects as a bone defect, as described here, can be used and similar advantageous Resulting effects.  

The molded body according to the invention has in terms of two outer ones made of a naturally occurring material Layers of the covering membrane forming the molded body Difference in porosity level based on that in it there is that typically the bone defect neat outer consisting of a naturally occurring material Layer has a higher degree of porosity, which indicates visibly the growth rate of cell material and Formation of a solid tissue structure is particularly advantageous is imprisoned. In addition, this high porosity allows that the bone defect is practically completely filled in and only then the mass reduction between the two outer ones layers consisting of a naturally occurring material layer, which comprises the plastic material, with controlled kinetics, so that per unit time only as much metabolic products are metabolized by the body, like the organism with a clinically irrelevant Can cope with foreign body reaction.

The different strength of the bone defect th layer (s) of the covering membrane forming the shaped body on the one hand and those who averted the bone defect th layer (s) is of great advantage, being more typical the outer one facing the bone defect from one naturally occurring material existing layer of the covering membrane  is much thicker than that of the bone defect turned outer consisting of a naturally occurring material Layer of the covering membrane. One reason for this is in the completion of that caused by the bone defect Cavity through the corresponding layers of Ab cover membrane or the molded body formed therefrom. No ben a resulting increased mechanical sta bility becomes a direct interaction of the outside Layer of the as a form, support and growth substrate the molded body with the remaining tissue ensures.

A volume of 1 to 5 mm ^{3 of} the individual pores, as shown, for example, in FIG. 2, of the outer membrane layer facing the bone defect, which is made of a natural material, is particularly suitable for promoting the ingrowth behavior of cells that cause the bone defect remove. This positive effect can be potentiated by the fact that a content of autologous bone material is present in the pores, which, without wishing to be determined hereinafter, serves as the starting point for particularly intensive growth of tissue that removes the bone defect.

Further features and advantages of the invention result emerge from the description below in which several Exemplary embodiments with reference to the schematic drawing explained in detail and examples of manufacture the Ab forming the molded body according to the invention cover membrane are listed.  

It shows:

Figure 1 is a schematic representation of the cross section through an embodiment of the cover membrane forming the Invention inventive body.

Figure 2 is a schematic representation of the cross section through a further embodiment of the covering membrane forming the inventive body.

Fig. 3 is a schematic perspective view of an embodiment of the moldings of the invention forming the covering membrane;

Fig. 4 is a schematic perspective view of an embodiment of an augmentation molded body according to the invention;

Figure 5 is a schematic representation of a cross section through the augmentation shaped body shown in Figure 4 according to the invention.

The prepared Figure 6 is a scanning electron micrograph in Example 1, the OF INVENTION to the invention form body forming Abdeckmem bran.

The produced 7 shows another scanning electron micrograph in Example 1, the moldings of the invention forming From covering membrane.

Fig. 1 shows an embodiment of the covering membrane forming the moldings according to the invention, which is composed of three layers, the two outer layers 1 and 1 'consisting of collagen and having a porous structure. Between the two outer layers of collagen there is an intermediate layer 2 consisting of a plastic material. The width of the two outer layers of naturally occurring material be larger than that of the intermediate layer 2 , which leads to the fact that a typical 5 to 10 mm wide collagen edge 3 exists, which is particularly suitable for the adaptation of the covering membrane to the area to be fixed Tissue or bone defect is suitable and also absorbs part of the mechanical stress that occurs.

The embodiment shown in FIG. 2 of the covering membrane forming the inventive body is characterized in that the outer layer 1 consisting of collagen has a significantly higher degree of porosity than the outer layer 1 'consisting of collagen. The highly porous collagen material from layer 1 also has bone substitute material 5 , which serves as the starting point for particularly intense tissue generation activity. The bioresorbable plastic material of the layer 2 lying between the two layers consisting of collagen prevents the cells from growing through layer 1 . Layer 1 'has a structure which is also locally active.

FIG. 3 again illustrates in the spatial representation the construction principle of the covering membrane that builds up the molded body according to the invention. Layer 1 , in the present case consisting of collagen, has a porous structure that particularly facilitates cell ingrowth. At layer 1 consisting of egg nem biodegradable plastic material includes to existing layer 2, the len under the influence of 'ingrowing into the lay from Kol existing layers 1 and 1 Zel intended purpose of these or their biochemical activities rule is dissolved. The last layer is layer 1 'in this three-layer embodiment of the covering membrane according to the present invention, which has a much more compact collagen structure that is cell-occlusive. Layer 1 also has a polymer matrix made of biodegradable plastic material, which gives the entire covering membrane increased mechanical stability due to its interconnecting effect.

Fig. 4 illustrates the basic structure of an augmentation molded body according to the invention for the elimination of bone defects. The particularly strongly embossed layer 1 consisting of collagen, which has a very high degree of porosity, is followed by layer 2 consisting of the biodegradable plastic material. The collagen layer 1 'facing away from the bone defect has a significantly lower porosity and thickness than layer 1 . Layer 1, due to its strength, allows the bone defect to be filled in and the direct contact to ensure rapid cell ingrowth. Polymer matrix 4 , made from biodegradable material, allows a special reinforcement of layer 1 and thus significantly increases the mechanical loading capacity of the shaped augmentation body, which has a major advantage, particularly in the case of large bone defects to be repaired.

FIG. 5 shows the augmentation molded body from FIG. 4 in cross section. The two outer layers 1 and 1 'give the best existing layer 2 made of biodegradable plastic.

The Ab forming the molded body according to the invention Deck membrane was manufactured using a process provides, based on the following games to be illustrated.

EXAMPLES

For all examples listed in Table 1 herein the following procedure was implemented:

A first collagen layer was made into a mold inserted and then the polymer in granular form (amount in grams) on the first collagen layer. The second layer of collagen was then applied to the Plastic material placed in granulate form, the factory stuff closed with a ram and as a whole placed in a high pressure autoclave.  

The high pressure autoclave was filled with CO ₂ , which was compressed using a piston diaphragm pump. The pressure p and the temperature T in the pressure vessel were set with means of the pressure increasing unit and temperature control unit. A temperature control of the autoclave used was in principle possible between -70 ° C and 400 ° C. After a gassing time, the pressure was released with an adjustable gradient. The tool was then removed from the high-pressure autoclave, opened and the three-layer covering membrane thus produced was removed from the tool according to the invention.

The test parameters can be found in Table 1 with PDLLA Poly (D, L-lactide) and TCP Tricalci umphosphate means.

The collagen layers used had a thickness of 0.2 mm, regardless of whether they are rectangular or circular were shaped.  

Table 1

All covering membranes produced in this way had egg ne high mechanical stability and were thermal deformable.

From FIGS. 6 and 7 it can be seen that the bioresorbable polymer layer is compact and the fiber structure of the collagen layers undamaged.

Claims (36)

1. Shaped body, which serves as a mold, support and growth substrate, comprising a covering membrane for tissue regeneration and / or bone regeneration, characterized in that the covering membrane has at least three layers, the two outer layers 1 , 1 'each being natural contain occurring material and at least one intermediate layer 2 consists of at least one plastic material, the layer 2 having a cell-exclusive porous or cell-exclusive non-porous structure. 2. Shaped body according to claim 1, characterized in that in addition to the layer 2 consisting of a plastic material, at least one further of the layers forming the covering membrane contains a polymer matrix made of plastic material. 3. Shaped body according to claim 1 or 2, characterized in that at least one of the two outer layers 1 , 1 'consisting of naturally occurring material contains a polymer matrix made of plastic material. 4. Shaped body according to claim 3, characterized in that the Polymer matrix is porous. 5. Shaped body according to one of claims 1 to 4, characterized characterized in that the consisting of plastic material Layer containing polymer matrix the tissue to be regenerated and / or facing bone. 6. Shaped body according to one of claims 1 to 5, characterized records that the plastic material from a thermoplastic be stands. 7. Shaped body according to claim 6, characterized in that the Thermoplastic at least one polyester from the family of poly-α- Hydroxy acids, especially polytrimethylene carbonate, polydioxa non, polyglycolide, polylactide, poly (L-lactide-co-glycolide) along with their copolymers with one another; Polyorthoesters and / or polyca prolacton, polyhydroxybutyrate or polyhydroxybutyrate-co-hydroxy has valerat.   8. Shaped body according to one of claims 1 to 7, characterized records that the plastic material is poly (D, L-lactide). 9. Shaped body according to one of claims 1 to 7, characterized indicates that the plastic material poly (L-lactid-co-D, L-lactid) is. 10. Shaped body according to claim 9, characterized in that the Plastic material has a weight ratio of L-lactide to D, L-lac tid of 40:60. 11. Shaped body according to claim 9, characterized in that the Plastic material has a weight ratio of L-lactide to D, L-lac tid of 50:50. 12. Shaped body according to claim 9, characterized in that the Plastic material has a weight ratio of L-lactide to D, L-lac tid of 70:30. 13. Shaped body according to claim 9, characterized in that the Plastic material has a weight ratio of L-lactide to D, L-lac tid of 80:20. 14. Shaped body according to one of claims 1 to 13, characterized in that at least one of the two outer layers 1 , 1 'has a content of collagen. 15. Shaped body according to one of claims 1 to 13, characterized in that at least one of the two outer layers 1 , 1 'consists of collagen. 16. Shaped body according to claim 14 or 15, characterized in that that the collagen is of type I and / or type IV. 17. Shaped body according to claim 15 or 16, characterized in that the two outer layers 1 , 1 'consist of collagen and both layers of collagen 1 , 1 ' have a porous structure. 18. Shaped body according to claim 15 or 16, characterized in that the two outer layers 1 , 1 'consist of collagen and a layer consisting of collagen has a porous structure and the other layer consisting of collagen has a smooth structure. 19. Shaped body according to claim 15 or 16, characterized in that the two outer layers 1 , 1 'consist of collagen and both layers consisting of collagen have a fibrous structure. 20. Shaped body according to claim 15 or 16, characterized in that the two outer layers 1 , 1 'consist of collagen and a layer consisting of collagen has a fibrous structure and the other layer consisting of collagen has a smooth structure. 21. Shaped body according to one of claims 15 to 20, characterized in that the covering membrane has a collagen edge 3 . 22. Shaped body according to claim 21, characterized in that the collagen edge 3 has a thickness of 5 to 10 mm. 23. Shaped body according to one of claims 1 to 22, characterized records that at least one of the covering membrane building Layers containing a bone substitute. 24. Shaped body according to claim 23, characterized in that at least one of the two outer layers 1 , 1 'and / or at least one layer between said outer layers 1 , 1 ' is mixed with a bone substitute material. 25. Shaped body according to one of claims 1 to 24, characterized records that at least one of the covering membrane building Layers and / or the bone replacement material contains min at least has a biologically active agent. 26. Shaped body according to claim 25, characterized in that at least one of the two outer layers 1 , 1 'and / or an intermediate layer between said outer layers and / or the bone substitute material contains at least one biologically active agent. 27. Shaped body according to claim 25 or 26, characterized in that the biologically active agent is selected from the group the growth factors, antibiotics, pain relievers, Agents that affect cell division and vascularization sen, coagulating and anti-coagulating agents, immunosuppressive lubricating and immunostimulating agents, cytokines, chemical Attractants, enzymes and combinations thereof.   28. Shaped body according to one of claims 1 to 27, characterized records that the cover membrane is three-dimensional, in particular is thermally deformed. 29. Shaped body according to one of claims 1 to 28, characterized in that the degree of porosity of the two outer layers 1 , 1 'of a naturally occurring material of the covering membrane forming the shaped body is different. 30. Shaped body according to claim 29, characterized in that the the bone defect facing outer, from a natural occurring material existing layer of the covering membrane has a higher degree of porosity than that of the bone defect turned outer layer made of a natural material the cover membrane. 31. Shaped body according to one of claims 1 to 30, characterized records that the thickness of the outer defect facing the bone defect layer of a naturally occurring material Cover membrane is different from the thickness of the bone defect facing away from a naturally occurring material existing layer of the covering membrane. 32. Shaped body according to claim 31, characterized in that the the bone defect facing outer from a naturally occurring the existing layer of the covering membrane is thicker than the outer one facing away from the bone defect from a natural one Material existing layer of the covering membrane.   33. Shaped body according to one of claims 1 to 32, characterized in that at least the individual pores of the bone defect facing outer layer of a naturally occurring material of the covering membrane have a volume of 1 to 5 mm ³ . 34. Shaped body according to one of claims 1 to 33, characterized records that at least the pores facing the bone defect ten outer made of a naturally occurring material Layer of the covering membrane contains an autologous bone mat ial. 35. Use of the shaped body according to one of claims 1 to 34 as a shaped augmentation body to remedy bone defects. 36. Use of the shaped body according to one of claims 1 to 34 for the controlled tissue regeneration and / or the controlled kno Chen regeneration.