Pasty, biocompatible material for use in a method for supporting bone regeneration, the composition thereof, and moulded part formed from the pasty material

Abstract

The invention relates to a pasty, biocompatible material for use in a method for supporting bone regeneration in a planar lesion not determined by surrounding bone material, on a bone base or in or on a bone, in particular in a jaw bone, wherein the pasty biocompatible material is designed, after filling in the planar lesions not determined by surrounding bone material, to cure and to form a dimensionally stable moulded part, wherein the material consists of or comprises between 50 wt.% and 70 wt.%, preferably 65 wt.%, of a calcium-containing base material, between 15 wt.% and 40 wt.%, preferably 20 wt.%, mineral trioxide aggregate (MTA) and between 15 wt.% and 25 wt.% of at least one antibiotic, between 0.1 wt.% and 1.0 wt.% of a liquid, preferably demineralised water or sodium chloride solution (NaCl), and the base material is completely resorbed once regeneration of bone material and / or bone augmentation is complete.

Description

[0001] Description

[0002] Pasty, biocompatible material for use in a method for supporting new bone formation, its composition and molded part formed from the pasty material

[0003] The present invention relates to a pasty, biocompatible material for supporting new bone formation in flat lesions on or in a bone, particularly a jawbone, that are not determined by surrounding bone material. In this context, "flat" refers to the situation where bone material has been resorbed to such an extent that only the bone base remains, but no surrounding bone material or bone walls. The latter is the case, for example, in a tooth extraction. The cavity created by the extraction is surrounded on four sides by bone material, which provides bone cells for independent regeneration and new bone formation.

[0004] The material consists of a combination of calcium-containing base material, mineral trioxide aggregate (MTA), antibiotic, and a liquid. The calcium-containing base material is completely resorbed, while the MTA remains in the newly formed bone.

[0005] To date, various materials have been used for bone repair and regeneration. However, many of these materials have the disadvantage of being insufficiently biocompatible or lacking sufficient stability and strength. Furthermore, existing materials are resorbed too quickly and therefore cannot be used for satisfactory bone augmentation. Known applications of MTA have only shown treatment success in small, clearly defined lesions surrounded by bone material on multiple sides.

[0006] In dentistry in particular, these conventional procedures have proven to be disadvantageous. When treating bone loss caused by periodontitis, it is important to fill large lesions with new bone material without removing the surrounding bone. Conventional replacement materials have the disadvantage that they resorb too quickly, meaning that new bone is not formed sufficiently. However, the newly formed bone material must be sufficiently stable and present in a quantity and depth appropriate to the original bone in order to be able to securely anchor implants, for example, in a follow-up treatment.

[0007] Until now, replacement pieces made from the patient's own bone material, taken from the jaw joint or hip bone, have been used, particularly in periodontal treatment. However, the associated procedures are complex and stressful for the patient, and not always successful.

[0008] The present invention overcomes the disadvantages of known materials and treatments by providing a pasty, biocompatible material specifically developed for new bone formation in flat lesions not determined by surrounding bone material. The material hardens after filling the lesions, forming a dimensionally stable molded part. The pasty material consists of a mixture of calcium-containing base material, mineral trioxide aggregate (MTA), antibiotic, and a liquid. In this context, "flat" refers to the situation where bone material has been resorbed to such an extent that only the bone base remains, but not the surrounding bone material or bone walls. The latter is the case, for example, with a tooth extraction.The cavity created by the extraction is surrounded on four sides by bone material, which provides bone cells for self-regeneration and new bone formation. The resulting dimensionally stable preform allows the migration of bone cells from the bone base and provides a stable base and scaffold structure for the formation of new bone and complete regeneration of the lesion, as well as sufficient bone augmentation.

[0009] The calcium-containing base material, which makes up between 50 wt.% and 70 wt.%, preferably 65 wt.% of the material, can come from a variety of sources, including aragonite, mussel shell, shell limestone, allogeneic bone material, autogenous bone material, xenogeneic bone material, FDBA (freeze-dried bone allocrafts), DFBA (decalcified freeze-dried bone allocrafts), algae or algae extract, ceramic, calcium phosphate, in particular tri- or tetracalcium phosphate, X- or ß-tricalcium phosphate, hydroxyl apatite, calcium phosphate ceramic, bioglass, aragonite-based bone substitute material (e.g. BioCoral®) or mixtures thereof.

[0010] In particular, it is also conceivable to produce the calcium-containing base material from donor bones. Calcium-containing base material produced from bones from bone banks is also encompassed by the invention. The invention also considers the use of FDBA (freeze-dried bone allocrafts) or DFDBA (decalcified freeze-dried bone allocrafts) to be advantageous. By forming the calcium-containing base material from material taken from a genetically different individual of the same species, bone growth can proceed optimally. The likelihood of inflammatory reactions is advantageously reduced. The use of xenogeneic materials for producing the calcium-containing base material has also proven advantageous. Bones from cattle, pigs, and horses are particularly suitable for producing calcium-containing base materials suitable for humans.It is also possible, and encompassed by the invention, to provide the calcium-containing base material from algae, in particular algae extracts, corals, or mussels. Mussel shells prove particularly suitable for the production of the calcium-containing base material, as they consist of a calcium-protein mixture, more precisely, aragonite, and can therefore be particularly well absorbed by the body.

[0011] It is also possible to produce the calcium-containing base material from autogenous material, i.e. material provided by the patient themselves. For this purpose, bone material is first removed from the patient, processed into powder or granules, and prepared for use in the pasty material according to the invention, which is inserted or implanted into the patient as part of a subsequent treatment. This minimizes the likelihood of inflammatory reactions occurring in the patient's body. Furthermore, it is possible to use alloplastic materials such as calcium phosphates, ceramics, or bioglasses to produce the calcium-containing base material. The mineral trioxide aggregate (MTA), which makes up between 15 and 40 wt.%, preferably 20 wt.% of the material, consists of a mixture of tricalcium silicate, dicalcium silicate, tricalcium aluminate, and gypsum.

[0012] In a preferred embodiment, the mineral trioxide aggregate (MTA) can additionally contain a substance that increases radiopacity, such as bismuth(III) oxide. The proportion of bismuth(III) oxide (Bi205) in the MTA component is then between 0.1 and 30 wt.%, preferably 20 wt.%. The antibiotic, which makes up between 10 wt.% and 25 wt.% of the material, can be selected from a variety of antibiotics, particularly those used in dentistry, or mixtures of several antibiotics.

[0013] The pasty, biocompatible material may also contain an additional substance that supports bone regeneration. This additional substance may be selected from the group consisting of statin, vitamin, trace element, hyaluronic acid, hyaluronic acid derivative, collagen, and / or mixtures thereof. The proportion of this additional substance in the material is preferably between 0.1 wt.% and 3 wt.%, in particular between 0.2 wt.% and 1.5 wt.%, preferably 0.25 wt.%.

[0014] The hyaluronic acid (or hyaluronic acid derivatives) usable in connection with the present invention has a beneficial effect on the treatment of pathological changes in the periodontium and exhibits positive effects on fibroblasts, bone regeneration, and wound healing. In connection with the present invention, hyaluronic acid (or its derivatives) can be added or mixed directly into the composition according to the invention. Alternatively, after preparing the pasty material and during insertion or application onto a bone substrate, the application site can be added or rinsed with a hyaluronic acid preparation. Hyaluronic acid has various functions in this context. The basic principle of action of hyaluronic acid in connection with the present invention is that, in an aqueous environment, three-dimensional mesh networks form as a result of spontaneous aggregation of the hyaluronic acid chains.Cellular and fibrous components can be embedded within this. This promotes and encourages the formation of a bone structure. At the same time, hyaluronic acid has a regulatory function in the organization of the extracellular matrix and its components. The resulting hyaluronic acid network is a prerequisite for metabolic exchange and simultaneously serves as a barrier against the penetration of foreign substances. Through the formation of the networks and their condensation, cells can be protected from degradation processes and hydroxyl radicals. The resulting hyaluronic acid shells serve as protection for various cell types against external influences, such as viral or bacterial ones, and thus also increase the survival rate of osteoblasts.Negatively charged hyaluronic acid also has the ability to bind large amounts of water and various plasma proteins via hydrogen bonding and its polar ends, thus acting as a kind of "osmotic buffer" of the extracellular matrix. Hyaluronic acid has also proven beneficial in combating chronic inflammation and exhibits anti-inflammatory potential. Hyaluronic acid also influences cellular growth factors, thus positively impacting cellular growth processes and supporting tissue regeneration. These numerous advantages are utilized in connection with the present invention and the composition.

[0015] Surprisingly, it has been shown that the regeneration of bone or bone material can be significantly improved. Surprisingly, it has been shown that the present invention enables a form of ossification or osteogenesis that is clearly superior to the prior art, particularly in patients in whom bone material has been resorbed to such an extent that only the bone base remains, but not the surrounding bone material or bone walls. In contrast, for example, in cavity-creating treatments such as tooth extractions, the cavity created by the extraction is surrounded on four sides by bone material. This provides bone cells for independent regeneration and new bone formation. In the case of flat lesions, however, spontaneous bone regeneration and augmentation from the bone base is not possible.

[0016] With regard to the further optional additives selected from the group consisting of statins, vitamins, trace elements, or mixtures thereof, vitamins and trace elements promote the supply of newly formed cells, while statins or statin preparations serve to modulate the immune system and thus reduce the tendency to inflammation. The invention is not limited to the aforementioned substances, but includes all substances and substance mixtures familiar to the person skilled in the art and usable in connection with the present invention.

[0017] The mineral trioxide aggregate (MTA) in the pasty material consists in particular of a mixture of tricalcium silicate, dicalcium silicate, tricalcium aluminate, and gypsum. The proportion of a mixture of tricalcium silicate (CaOs SiC t e ), dicalcium silicate (CaO2 SiO 2 ), and tricalcium aluminate (CaOs Al O s ) in the MTA is preferably between 70 and 80 wt.%, preferably 75 wt.%, while the proportion of gypsum (CaSO4 2 H 2 O) is between 1 and 10 wt.%, preferably 5 wt.%. The pasty, biocompatible material is used to form a dimensionally stable molded part after curing. This molded part is formed by applying the pasty material to the remaining bone base in a flat lesion under the periosteum, not determined by surrounding bone material, and then allowing it to cure. The periosteum covers the lesion and is preferably injected with the pasty material.

[0018] The pasty, biocompatible material to support bone regeneration and / or bone augmentation consists of 50 wt.% to 70 wt.% calcium-containing base material, 15 wt.% to 40 wt.% mineral trioxide aggregate (MTA), 15 wt.% to 25 wt.% of one or more antibiotics and 0.1 wt.% to 1.0 wt.% of a liquid, which is preferably demineralized water or saline solution (NaCl). The calcium-containing base material can come from various sources, such as aragonite, mussel shell, allogeneic bone material, autogenous bone material, xenogeneic bone material, FDBA (freeze-dried bone allocrafts), DFBA (decalcified freeze-dried bone allocrafts), algae or algae extract, ceramic, calcium phosphate (especially tri- or tetracalcium phosphate, X- or ß-tricalcium phosphate, hydroxyl apatite), calcium phosphate ceramic, bioglass, aragonite-based bone substitute material (e.g.Bi- oCoral®) or mixtures thereof. The antibiotic can be selected from a group of antibiotics used particularly in dentistry, or mixtures thereof. Examples of antibiotics are penicillin, amoxicillin, clindamycin, metronidazole, erythromycin, tetracycline, doxycycline, ciprofloxacin, levofloxacin, azithromycin, minocycline, lincomycin, gentamicin, vancomycin, moxifloxacin, rifampicin, sulfamethoxazole / trimethoprim, amikacin, ceftazidime, ceftriaxone, imipenem, meropenem, ampicillin, chloramphenicol, nystatin, ketoconazole, fluconazole, or voriconazole, without limiting the invention thereto.

[0019] Surprisingly, it has been shown that the non-resorbable MTA in the biocompatible molded part exhibits several beneficial effects on new bone formation, thus enabling a significantly higher rate of bone growth. During the course of new bone formation, particularly in the jawbone, the calcium-containing base material is resorbed, but the non-resorbable mineral trioxide aggregate (MTA) remains in the newly formed bone material in the filled bone lesion and is incorporated into the newly forming bone substance. During the resorption of the calcium-containing base material, the mineral trioxide aggregate (MTA) forms a scaffold structure. During the course of new bone formation, osteoclasts degrade the calcium-containing base material and thus provide the basis for the settlement of osteoblasts in the cavities formed by the degradation.The bone structure surrounding the cavities is additionally stabilized by mineral trioxide aggregate (MTA), and the period during which bone growth is possible is thus extended. This results in greater, i.e. higher bone augmentation and enables the formation of new bone in larger bone sections or lesions. This is also the case in patients in whom only the bone base remains. Mineral trioxide aggregate (MTA) also provides a basis for cell growth, as bone cells attach to the mineral trioxide aggregate (MTA), thus additionally promoting new bone formation. The bone augmentation of an existing bone structure is significantly improved. In particular, bone augmentation of up to 1.8 to 2.0 cm is possible.Mineral Trioxide Aggregate (MTA) has the further advantage of having a blood-binding effect immediately after the surgical procedure and also has an anti-inflammatory effect due to the establishment of a basic pH value in the surgical area.

[0020] During use, i.e., during the course of bone formation, the molded part formed from the hardened paste-like material in the lesion is resorbed down to the mineral trioxide aggregate (MTA) content. This resorption is accompanied by a corresponding filling of the lesion with newly formed bone material or the filling with osteoblasts, which initiate or carry out osteogenesis.

[0021] This invention thus provides an improved pasty, biocompatible material to support new bone formation and bone augmentation, which has been specifically developed for the treatment of lesions on or in bones, in particular jawbones, where only the bone base is present but no surrounding bone material or bone walls are present.

[0022] The present invention also relates to a composition for producing a pasty, biocompatible material for use in flat lesions on or in a bone, in particular in a jawbone, which are not determined by surrounding bone material. The composition consists of a calcium-containing, structural base material, mineral trioxide aggregate (MTA), and at least one antibiotic. The calcium-containing structural base material can be selected from a variety of materials, including aragonite, mussel shell, allogeneic bone material, autogenous bone material, xenogeneic bone material, FDBA (freeze-dried bone allocrafts), DFBA (decalcified freeze-dried bone allocrafts), algae or algae extract, ceramic, calcium phosphate (in particular tri- or tetracalcium phosphate, β- or β-tricalcium phosphate, hydroxyl apatite), calcium phosphate ceramic, bioglass, aragonite-based bone substitute material (e.g., BioCoral®), or mixtures thereof.

[0023] The mineral trioxide aggregate (MTA) in composition consists of or includes tricalcium silicate (CaOs SiCte), dicalcium silicate (CaC^ SiCte), tricalcium aluminate (CaOs A^Os) and gypsum (CaSO4-2 H2O).

[0024] In a preferred embodiment, the composition of the mineral trioxide aggregate (MTA) additionally comprises a radiopacity-increasing substance, in particular bismuth(III) oxide (Bi205), in an amount between 0.1 and 30 wt.%, preferably 20 wt.%.

[0025] The composition also contains at least one antibiotic selected from a group of antibiotics particularly suitable for use in dentistry, preferably in bone regeneration.

[0026] The composition typically consists of 50 wt% to 70 wt%, preferably 65 wt% of the calcium-containing base material, 15 wt% to 40%, preferably 20% of the mineral trioxide aggregate (MTA) and 15% to 25% of the antibiotic.

[0027] The mineral trioxide aggregate (MTA) is available in powder or granular form and is homogeneously distributed throughout the base material. These properties enable easy handling and application of the composition.

[0028] The composition according to the invention offers an improved treatment option for bone lesions, particularly in the jawbone, by promoting tissue regeneration and wound healing and creating a suitable environment for the cells.

[0029] To produce the pasty, biocompatible material, the previously described powdered components (calcium-containing structural base material, mineral trioxide aggregate (MTA), antibiotic(s), and optionally other aforementioned substances) are first mixed. The liquid, preferably demineralized water or saline solution (NaCl), is then added and stirred to the desired consistency. The pasty material can then be drawn up with an injection syringe and injected into the lesion.

[0030] The present invention also relates to a biocompatible molded part for use in a method for supporting new bone formation, in particular for bone augmentation of an existing bone structure. The biocompatible molded part is characterized in that it is formed from a pasty material as described above after a flat lesion on or in a bone, in particular in a jawbone, not determined by surrounding bone material, has been treated with the pasty material. The molded part consists of a calcium-containing, structural base material, mineral trioxide aggregate (MTA), and at least one antibiotic.

[0031] It is considered advantageous if the molded part contains between 50 wt.% and 70 wt.%, preferably 65 wt.% of the calcium-containing base material, between 15 wt.% and 40 wt.%, preferably 20 wt.% of the mineral trioxide aggregate (MTA) and between 15 wt.% and 25 wt.% of at least one antibiotic.

[0032] In addition, the molded part can in particular contain at least one further substance. The further substance can be selected from the group consisting of statin, vitamin, trace element, hyaluronic acid, hyaluronic acid derivative, collagen, and / or mixtures thereof. The proportion of the further substance in the molded part is in particular between 0.1 wt.% and 3 wt.%, preferably between 0.2 wt.% and 1.5 wt.%, with 0.25 wt.% being preferred.

[0033] When used in a process to support new bone formation, particularly in a jawbone, the molded part provides a basic structure for new bone formation. The base material and the antibiotic are completely resorbed during bone formation, while the mineral trioxide aggregate (MTA) remains in the newly formed bone. The molded part enables the filling of flat lesions on or in a bone, particularly in a jawbone, that are not clearly defined by surrounding bone material or where only the bone base is present, but no surrounding bone material or bone walls.

[0034] The molded part is preferably formed in situ in a flat, not surrounded by surrounding

[0035] A lesion determined by bone material is formed on or in a bone from a hardened, pasty material. In a preferred embodiment, the molded part is formed directly in the lesion after injection of a periosteum covering the flat lesion not determined by surrounding bone material, thus adapting it to its shape and extent.

[0036] The present invention enables effective support of new bone formation and bone augmentation in existing bone structures. The biocompatible molded part provides a structural base and is resorbed during bone formation, while the mineral trioxide aggregate (MTA) remains in the bone. Additional benefits can be achieved by adding other substances.

[0037] The invention also relates to mineral trioxide aggregate (MTA) for use in the treatment of bone deficiencies, in particular in the treatment of periodontitis in a biocompatible molded part made of a pasty material, wherein the filling of a flat lesion not determined by surrounding bone material on or in a bone, in particular in a jawbone, is provided.

[0038] The present invention relates to a mineral trioxide aggregate (MTA) specifically developed for the treatment of bone deficiencies, particularly periodontal disease. Periodontal disease is a disease characterized by a loss of bone tissue around the teeth, leading to a weakening of the periodontal ligament. Various bone regeneration methods are used to counteract these bone deficiencies.

[0039] Mineral trioxide aggregate (MTA) has been used in dentistry primarily for bacteria-tight, retrograde root canal closure in apical surgery.

[0040] Surprisingly, it has been shown that mineral trioxide aggregate (MTA) promotes new bone formation in flat lesions on or in a bone, particularly in a jawbone, which are not clearly defined by surrounding bone material. In such flat lesions, the migration of bone cells into the treatment area is difficult because, unlike in cavities that are undergoing degeneration, there is no surrounding bone tissue, and migration can only occur from one side / surface. Mineral trioxide aggregate (MTA) significantly promotes the treatment of bone defects, for example, those resulting from periodontitis.Due to the original purposes of MTA in dental therapy as a sealing material for root canals and perforations in milk teeth or in the filling of cavities, the use of mineral trioxide aggregate (MTA) in the treatment of flat lesions or bone deficits on or in a bone, particularly in a jawbone, which are not clearly determined by surrounding bone material through new formation of bone material to fill defects in bone after operations or disease-related bone loss or the formation of bone lesions where filling with newly formed bone material is indicated and particularly in the treatment of periodontitis is new and not obvious to the expert.

[0041] Mineral trioxide aggregate (MTA) is known from its use in the field of maxillofacial surgery and is suitable for this purpose. However, its use as described above in a pasty, biocompatible material and a molded part formed therefrom according to the present invention have not been known to date. This has surprisingly led to a significant improvement in bone regeneration, particularly in the treatment of periodontal bone damage. Due to the lack of resorption, mineral trioxide aggregate (MTA) provides the molded part or solid body with good stability over a long period of time during bone growth.

[0042] At the same time, mineral trioxide aggregate (MTA) promotes cell growth and the ingrowth of blood vessels. Mineral trioxide aggregate (MTA) is also able to bind and stabilize blood clots that are forming. This increases the chances that blood vessels can grow simultaneously throughout the lesion. These vessels supply nutrients to the osteoblasts, allowing ossification or osteogenesis to occur, during which new bone material is formed and, for example, jawbone damaged by periodontitis can be rebuilt.

[0043] The molded part, which is preferably formed in situ, is more dimensionally stable over a longer period of time than known molded parts and can be individually dimensioned so that after sufficient ossification or osteogenesis, ie when no supporting structure is required anymore, the resorption process is completed and mineral trioxide aggregate (MTA) continues to remain in the bone as a supporting matrix.

[0044] According to the present invention, mineral trioxide aggregate (MTA) is used in a pasty material that is molded into a biocompatible molded part. This molded part allows for precise placement of the mineral trioxide aggregate (MTA) at the affected sites, particularly in flat lesions that are not determined by surrounding bone material. This is particularly advantageous in the treatment of periodontitis, as it allows for targeted and effective filling of bone deficiencies.

[0045] The use of mineral trioxide aggregate (MTA) in a biocompatible molded component offers several advantages. First, it enables improved adhesion and fixation of the mineral trioxide aggregate (MTA) to the target sites, ensuring long-term stability and efficacy. Second, the biocompatible material of the molded component ensures minimal irritation and good compatibility with the surrounding tissue, leading to a reduced inflammatory response and faster healing.

[0046] The use of the mineral trioxide aggregate (MTA) and the biocompatible molded part containing it is particularly preferred for the treatment of periodontal disease in the jawbone. Jawbone is susceptible to bone deficiencies due to periodontal disease, and the targeted use of the mineral trioxide aggregate (MTA) in combination with the biocompatible molded part can lead to effective bone regeneration.

[0047] Overall, the present invention offers an improved solution for the treatment of bone deficiencies.

[0048] The beneficial effect of the material according to the invention is also confirmed by clinical studies.

[0049] In a patient, the pasty material according to the invention was implanted under local anesthesia in a region with reduced jawbone under the periosteum and the biocompatible molded part was formed there in situ.

[0050] The pasty material was prepared by mixing 60 wt% shell limestone,

[0051] 20 wt% mineral trioxide aggregate (MTA) and

[0052] 20 wt.% of an antibiotic, each in powder form Addition of less

[0053] Drops of saline solution (NaCl)

[0054] Manufactured, drawn up using a conventional cannula and then injected under the periosteum to the desired later level of bone augmentation.

[0055] Six months after treatment, a bone cylinder measuring a maximum of 0.7 cm in length and 0.2 cm in diameter was taken from the region where new bone had formed, and this sample was used to determine the regenerative potential of the material. Thin sections were prepared for histological analysis and examined microscopically.

[0056] Microscopic evaluation revealed the formation of vital corticocancellous bone with focal osteoblastic margins and relatively fresh newly formed bone. Focally, amorphous material and extremely few, tiny, non-vital necrotic bone fragments were visible.

[0057] The results showed predominantly vital, partially fresh corticocancellous bone with signs of ingrowth and medullary fibrosis. Focal foreign body reactions in the connective tissue and amorphous material occurred. Overall, however, only microfocal evidence of non-vital necrotic bone or bone substitute material was detectable. However, the vast majority of vital bone had developed, with fresh bone and new bone formation as signs of regeneration. No evidence of florid osteomyelitis and no indication of malignancy was found.

[0058] Similar findings were found in five other patients examined.

[0059] Further advantages and practical features can be found in the figure description and the drawing. It shows:

[0060] Fig. 1 shows the situation of a lesion before treatment in a schematic representation, Fig. 2 shows the situation after filling the lesion and forming the biocompatible molded part according to the invention in a schematic representation,

[0061] Fig. 3 the situation with completely regenerated lesion and completed bone augmentation in a schematic representation

[0062] Fig. 1 : Situation of a lesion before treatment

[0063] Fig. 1 shows a schematic representation of the situation of a lesion 1 immediately after treatment with the pasty material of the invention. This was a flat lesion 1 in which the surrounding bone material 2 had been resorbed, leaving only the bone base 3. This can occur, for example, in periodontitis in the jawbone. Remaining teeth 4 can be seen in Fig. 1, outside the resorbed bone structure. The resulting space 5 is, unlike in extractions, not surrounded by bone material that could ensure the regeneration and formation of new bone cells. The lesion 1 is covered by periosteum 8.

[0064] Fig. 2 shows a schematic representation of the situation after filling the lesion 1 with the pasty, biocompatible material 6. The material 6 has hardened and has formed a dimensionally stable molded part 7 in the lesion 1. This creates a stable base and framework structure that allows the bone cells to penetrate into the lesion 1 and form new bone. In Fig. 2, the molded part 7 was formed in situ in a flat lesion 1 not determined by surrounding bone material on the remaining bone base 3 from the pasty material of the present invention and after its hardening. The molded part 7 is injected after a periosteum 8 covering the lesion directly in the lesion 1 and thus on its

[0065] Shape and extent coordinated, formed on the bone base 3.

[0066] The non-resorbable MTA 10 in the biocompatible molded part 7 enables a significantly higher growth of bone material. During the course of new bone formation, particularly in the jawbone, the calcium-containing base material 11 is resorbed, but the non-resorbable mineral trioxide aggregate (MTA) remains in the newly formed bone material in the filled lesion 1 and is incorporated into the newly forming bone substance. During the resorption of the calcium-containing base material, the mineral trioxide aggregate (MTA) forms a scaffold structure. During the course of new bone formation, osteoclasts break down the calcium-containing base material and thus provide the basis for the settlement of osteoblasts in the cavities formed by the breakdown. The bone structure surrounding the cavities is additionally stabilized by the mineral trioxide aggregate (MTA), and the period during which bone growth is possible is thus extended. This results in a larger, i.e.i.e. higher bone augmentation or it enables the formation of new bone in larger bone sections or lesions 1 . This is also the case in patients in whom, as shown in Fig. 1 , only the bone base 3 is still present. Mineral trioxide aggregate (MTA) also provides a basis for cell growth, as bone cells attach to the mineral trioxide aggregate (MTA), thus additionally promoting new bone formation. The bone augmentation of an existing bone structure is significantly improved. In particular, bone augmentation of up to between 1.8 and 2.0 cm is possible. Mineral trioxide aggregate (MTA) has a further advantage in that it has a blood-binding effect directly after the surgical intervention and, by establishing a basic pH value in the surgical area, also has an anti-inflammatory effect.

[0067] Fig. 3 shows a schematic representation of the situation after complete regeneration of lesion 1 and bone augmentation. The pasty material has led to the formation of new bone adjacent to the existing bone material and enhancing the bone base 3, which has completely regenerated lesion 1. This provides a sufficient amount and height of bone to securely anchor implants 9, for example.

Claims

Claims 1. Pasty, biocompatible material for use in a method for supporting new bone formation in a flat lesion (1) on a bone base (3) or in or on a bone, in particular in a jawbone, wherein the pasty, biocompatible material is designed to harden after filling the flat lesions (1) not determined by surrounding bone material and to form a dimensionally stable molded part (7), wherein the material consists of: between 50 wt.% and 70 wt.%, preferably 65 wt.% of a calcium-containing base material, between 15 wt.% and 40 wt.%, preferably 20 wt.% of mineral trioxide Aggregate (MTA) and between 15 wt.% and 25 wt.% of at least one antibiotic, between 0.1 wt.% and 1.0 wt.% of a liquid, preferably demineralized water or saline solution (NaCl), and wherein the base material is completely resorbed until the completion of new bone formation and / or bone augmentation.

2. Pasty, biocompatible material according to claim 1, characterized in that the base material is selected from the group consisting of: aragonite, mussel shell, shell limestone, allogenic bone material, autogenous bone material, xenogenic bone material, FDBA (freeze-dried bone allocrafts), DFBA (decalzed freeze-dried bone allocrafts), algae or algae extract, ceramic, calcium phosphate, in particular tri- or tetracalcium phosphate, X- or ß-tricalcium phosphate, hydroxyl apatite, calcium phosphate ceramic, bioglass, bone replacement material based on aragonite (e.g. BioCoral ®) or mixtures thereof, the mineral trioxide aggregate (MTA) comprises or consists of tricalcium silicate (CaOs SiCte), dicalcium silicate (CaC^ SiCte), tricalcium aluminate (CaOs A^Os) and gypsum (CaSO4-2 H2O), and the antibiotic is selected from the group comprising or consisting of penicillin, amoxicillin, clindamycin, metronidazole, erythromycin, tetracycline, doxycycline, ciprofloxacin, levofloxacin, azithromycin, minocycline, lincomycin, gentamicin, vancomycin, moxifloxacin, rifampicin, sulfamethoxazole / trimethoprim, amikacin, ceftazidime, ceftriaxone, imipenem, meropenem, ampicillin, chloramphenicol, nystatin, ketoconazole, fluconazole or voriconazole or mixtures thereof.

3. Pasty, biocompatible material according to claim 1 or 2, characterized in that the material contains at least one further substance, in particular wherein the at least one further substance is selected from the group consisting of statin, vitamin, trace element, hyaluronic acid, hyaluronic acid derivative, collagen and / or mixtures thereof, wherein the at least one further substance in particular has a proportion of between 0.1 - 3 wt.%, in particular of between 0.2 - 1.5 wt.%, preferably 0.25 wt.% of the pasty, biocompatible material.

4. Pasty, biocompatible material according to one of the preceding claims, characterized in that the mineral trioxide aggregate (MTA) comprises between 70 and 80 wt.%, preferably 75 wt.% of a mixture of Tricalcium silicate (CaOs SiCte), dicalcium silicate (CaC^ SiCte), tricalcium aluminate (CaOs A^Os), and between 1 and 10 wt.%, preferably 5 wt.% gypsum (CaSO4'2 H2O).

5. Pasty, biocompatible material according to one of the preceding claims, characterized in that mineral trioxide aggregate (MTA) comprises a substance that increases radiopacity, in particular bismuth(III) oxide (Bi2O3).

6. Pasty, biocompatible material according to claim 5, characterized in that mineral trioxide aggregate (MTA) contains between 0.1 and 30 wt.%, preferably 20 wt.%, of bismuth(III) oxide (Bi205).

7. Pasty, biocompatible material according to one of the preceding claims, characterized in that the dimensionally stable molded part (7) is formed after injection of a periosteum covering the flat lesion not determined by surrounding bone material after curing of pasty, biocompatible material.

8. Pasty, biocompatible material for supporting the formation of new bone material and / or for bone augmentation in a mammalian bone by forming a shaped part after curing, wherein the pasty biocompatible material consists of between 50 wt.% and 70 wt.%, preferably 65 wt.% of a calcium-containing base material, between 15 wt.% and 40 wt.%, preferably 20 wt.% of mineral trioxide Aggregate (MTA), between 15 wt% and 25 wt% of at least one antibiotic and - consists of or comprises between 0.1 wt.% and 1.0 wt.% of a liquid, preferably demineralized water or saline solution (NaCl), wherein the calcium-containing base material is selected from the group consisting of: aragonite, mussel shell, shell limestone, allogenic bone material, autogenous bone material, xenogenic bone material, FDBA (freeze-dried bone allocrafts), DFBA (decalzed freeze-dried bone allocrafts), algae or algae extract, ceramic, Calcium phosphate, in particular tri- or tetracalcium phosphate, X- or ß-tricalcium phosphate, hydroxyl apatite, calcium phosphate ceramic, bioglass, aragonite-based bone substitute material (e.g. BioCoral ®) or mixtures thereof, the mineral trioxide aggregate (MTA) comprises or consists of tricalcium silicate (CaOs SiCte), dicalcium silicate (CaC^ SiCte), tricalcium aluminate (CaOs A^Os) and gypsum (CaSO4-2 H2O), and the antibiotic is selected from the group consisting of penicillin, amoxicillin, clindamycin, metronidazole, erythromycin, tetracycline, doxycycline, ciprofloxacin, levofloxacin, azithromycin, minocycline, lincomycin, gentamicin, vancomycin, moxifloxacin, rifampicin, Sulfamethoxazole / trimethoprim, amikacin, ceftazidime, ceftriaxone, imipenem, meropenem, ampicillin, chloramphenicol, nystatin, ketoconazole, fluconazole or voriconazole or mixtures thereof. Composition for producing a pasty biocompatible material according to one of claims 1 to 8, in particular for use in a flat lesion (1) not determined by surrounding bone material on a bone base (3) or on or in a bone, in particular in a jawbone, comprising or consisting of a calcium-containing, structural base material, Mineral trioxide aggregate (MTA) and at least one antibiotic, wherein the calcium-containing structural base material is selected from the group consisting of aragonite, mussel shell, shell limestone, allogeneic bone material, autogenous bone material, xenogeneic bone material, FDBA (freeze-dried bone allocrafts), DFBA (decalzified freeze-dried bone allocrafts), algae or algae extract, ceramic, calcium phosphate, in particular tri- or tetracalcium phosphate, X- or ß-tricalcium phosphate, hydroxyl apatite, calcium phosphate ceramic, bioglass, aragonite-based bone replacement material (e.g. BioCoral ®) or mixtures thereof, the mineral trioxide aggregate (MTA) comprises or consists of tricalcium silicate (CaOs SiCte), dicalcium silicate (CaC^ SiCte), tricalcium aluminate (CaOs A^Os) and gypsum (CaSO4-2 H2O), and the at least one antibiotic is selected from the group consisting of penicillin, amoxicillin, clindamycin, metronidazole, erythromycin, tetracycline, doxycycline, ciprofloxacin, levofloxacin, azithromycin, minocycline, lincomycin, gentamicin, vancomycin, moxifloxacin, rifampicin, sulfamethoxazole / trimethoprim, amikacin, ceftazidime, ceftriaxone, imipenem, meropenem, ampicillin, chloramphenicol, nystatin, ketoconazole, fluconazole or voriconazole or mixtures thereof.

10. Composition according to claim 9, characterized in that the composition - between 50 wt.% and 70 wt.%, preferably 65 wt.% of the calcium-containing base material, - between 15 wt% and 40 wt%, preferably 20 wt% of the mineral trioxide aggregate (MTA) and - comprises or consists of between 15% by weight and 25% by weight of at least one antibiotic.

11. Composition according to one of claims 9 or 10, characterized in that mineral trioxide aggregate (MTA) comprises a substance which increases the radiopacity, in particular bismuth(III) oxide (Bi205).

12. Composition according to claim 11, characterized in that mineral trioxide aggregate (MTA) comprises between 0.1 and 30 wt.%, preferably 20 wt.%, of bismuth(III) oxide (Bi205).

13. Composition according to one of claims 9 to 12, characterized in that the mineral trioxide aggregate (MTA) is provided in powder form or as granules.

14. Composition according to one of claims 9 to 13, characterized in that the mineral trioxide aggregate (MTA) is provided in powder form or as granules.

15. Composition according to one of claims 9 to 14, characterized in that the mineral trioxide aggregate (MTA) is homogeneously distributed in the base material.

16. Biocompatible molded part (7) for use in a method for supporting new bone formation, in particular for bone augmentation of an existing bone structure, characterized in that the biocompatible molded part (7) is formed from a pasty material according to one of claims 1 to 8 after filling a flat lesion not determined by surrounding bone material on a bone base (3) or on or in a bone, in particular in a jawbone, and consists of a calcium-containing, structuring base material, mineral trioxide aggregate (MTA) and at least one antibiotic.

17. Biocompatible molded part according to claim 16, characterized in that the molded part (7) contains between 50 wt.% and 70 wt.%, preferably 65 wt.% of the calcium-containing base material, between 15 wt.% and 40 wt.%, preferably 20 wt.% of the mineral trioxide aggregate (MTA) and - contains between 15% and 25% by weight of at least one antibiotic.

18. Biocompatible molded part according to claim 16 or 17, characterized in that the molded part (7) contains at least one further substance, in particular wherein the at least one further substance is selected from the group consisting of statin, vitamin, trace element, hyaluronic acid, hyaluronic acid derivative, collagen and / or mixtures thereof, wherein the at least one further substance in particular contains a A proportion of between 0.1 - 3 wt.%, in particular between 0.2 - 1.5 wt.%, preferably 0.25 wt.% of the molded part.

19. Biocompatible molded part according to one of claims 16 to 18, characterized in that the molded part (7) when used in a method for supporting new bone formation, in particular in a jawbone, provides a basic structure for new bone formation, in particular for bone augmentation of an existing bone structure and the base material and the antibiotic are completely resorbed in the course of new bone formation and the mineral trioxide aggregate (MTA) remains in the newly formed bone.

20. Biocompatible molded part according to claim 19, characterized in that the molded part (7) is formed in situ in a flat lesion not determined by surrounding bone material on a bone base (3) or on or in a bone from a hardened, pasty material.

21. Biocompatible molded part according to claim 20, characterized in that the molded part (7) is formed after injection of a periosteum (8) covering the flat lesions not determined by surrounding bone material.

22. Mineral trioxide aggregate (MTA) for use in the treatment of bone deficiencies, in particular in the treatment of periodontitis in a biocompatible molded part (7) formed from a pasty material according to any one of claims 1 to 8.

23. Mineral trioxide aggregate (MTA) for use in the treatment of bone deficiencies, in particular in the treatment of periodontosis in a biocompatible molded part (7) formed from a pasty material according to one of claims 1 to 8, wherein the filling of a flat lesion not determined by surrounding bone material on a bone base (3) or on or in a bone, in particular in a jawbone, is provided.

Images