An implant composed of a substrate material infiltrated with a bioactive donor material and a method for manufacturing the same

Abstract

The present invention relates to an implant (1) for implantation into a patient, having an implant body which is at least partially absorbable and at least partially porous in regions, the implant body being composed of a ceramic base material (2), the base material being provided with a donor material (3) which releases ions for influencing the cell metabolism of the patient in the implanted state, wherein the donor material (3) penetrates into the base material (2). Furthermore, the present invention also relates to a method for manufacturing such an implant (1).

Description

Technical Field

[0001] The present invention relates to an implant for implantation into the body of a (human) patient, such as an intracranial implant. Additionally, the present invention also relates to a method for manufacturing such an implant. Background Art

[0002] An implant is herein a medical device external to the body that is placed into the body of a human or animal and that generally remains in the body for a determined period of time. An intracranial implant is herein a cranial implant, i.e., an implant used in the region of the human or animal skull.

[0003] Absorbable / bioresorbable components / materials are materials / substances that are bioabsorbable by the (patient's) body.

[0004] Cell metabolism or metabolism includes all physical and chemical processes in the body that convert chemical raw materials into semi-finished and finished products.

[0005] Ceramic or non-ceramic bone regeneration products available on the market or known as components of implants are particulate materials, curable cements, or prefabricated bodies with simple standard geometries. Here, there are few implants that are patient-specific and have a personalized three-dimensional matching shape, structure, and bioactive configuration.

[0006] Materials with bioactivity or bioactive substances are interactive substances that cause a positive cell response and / or "repair" body tissue.

[0007] Coating an implant with a bioactive (coating) is well-known, where there are stability problems with such a coating for the implant and it is not suitable for long-term activity

[0008] In addition, ceramic materials directly placed into the patient's body as particulate materials or viscous pastes are well-known. Such implants do not allow pre-implant shaping of a specific structure and geometry. Such implants with a gradient distribution of micropores can only be manufactured by randomly changing the implant composition.

[0009] Thus, for example, a medical device is known from EP 0 923 953 B1, which has at least one part that can be implanted into a patient's body. Here, at least a part of the device part is covered with a coating for releasing at least one bioactive material, wherein the coating includes a lower layer having an outer side surface and including a polymeric material that contains a large amount of bioactive material therein for timed release therefrom. Additionally, the coating includes a discontinuous covering layer, the covering range of which is less than the entire outer side surface of the lower layer, wherein the covered and uncovered areas are formed by the entire outer side surface of the lower layer. The covering layer includes a polymeric material that does not contain micropores and porogens.

[0010] Furthermore, US 7 101 394 B2 discloses a medical device that delivers bioactive material to a patient's body. The first covering layer has a bioactive material and optionally has a polymeric material that is disposed on the surface of the medical device. The second covering layer having magnetic microparticles and a polymeric material is disposed on the first covering layer. The second covering layer substantially free of bioactive material protects the bioactive material. SUMMARY OF THE INVENTION

[0011] In this context, the object of the present invention is to alleviate or prevent problems in the prior art and to provide a particularly durable or stable implant that better allows ingrowth of body tissue than conventional implants.

[0012] This object of the present invention is achieved by an implant, in particular in such a way that the implant has an at least partially absorbable and at least in part porous implant body made of a ceramic base material, such as α-TCP, β-TCP, hydroxyapatite, biphasic calcium phosphate, bioglass, β-SiAION or a bioresorbable photopolymer. Here, the base material is provided according to the present invention with a donor material that releases ions for influencing the metabolism of the patient's cells in the implanted state, and the donor material penetrates into the base material. Furthermore, according to the present invention, the ion-releasing bioactive donor material is arranged in the implant in an inherent structure and does not exist in the form of an implant coating.

[0013] The inherent bioactivity means that the bioactivity is a property of the implant itself, rather than just being externally applied to the implant. That is to say, the donor material is present throughout the implant volume. One such implant of the present invention enables optimal growth of body soft tissues and new bone formation. At the same time, the growth improves the strength of the implant. Additionally, the implant of the present invention has a longer-term bioactivity than, for example, a coated implant, because the bioactivity of the implant of the present invention comes from within (is inherent), rather than only the surface being active as in a coated implant.

[0014] Advantageous embodiments are the subject matter of the dependent claims and are described in detail below.

[0015] It can be considered that the donor material has ceramic and / or metal microparticles. Here it is stipulated that the ceramic microparticles are bioresorbable. Such materials are particularly suitable for releasing ions and thus have absorbability and bioactivity.

[0016] In addition, it is suitable for the implant to be divided into layers or partial regions of different densities and / or porosities. Thus, the bioactivity is controlled by the layer geometry of the implant and by the ions released from the storage material. Additionally, such an implant is particularly well-suited for body tissue growth.

[0017] It is also advantageous if the individual micropores in the implant are interconnected via connecting channels. Such connecting channels connect the micropores to each other, such that they allow the exchange of substances between or beyond the micropores and thus enable improved and longer-lasting ion release.

[0018] It can also be imagined that the donor material is arranged and concentrated in the base material such that when ions are released in the implanted state, connecting channels (secondary connecting channels) are compulsorily generated, or connecting channels (primary connecting channels) already exist in the implant before it is implanted into the patient's body. The implanted state is a state in which the implant has been implanted into a patient's body or already exists in the patient's body.

[0019] Preferably, the implant has a total porosity between 3% and 60%, particularly between 5% and 10%, preferably between 25% and 30%, further preferably between 50% and 60% and particularly preferably between 75% and 80%. The total porosity within this range is particularly favorable for ingrowth of the implant.

[0020] Furthermore, it is advantageous if the micropores in the implant have a size in the range of 300 μm to 1500 μm, in particular 350 μm to 450 μm, 800 μm to 900 μm, 1000 μm to 1200 μm. The pore size is predefined in terms of planning and then precisely implemented in terms of construction. Thus, the pore size does not occur randomly. By selecting the pore size suitable for the corresponding application, the mechanical conditions can be optimized while achieving the largest possible porosity, and enabling perfect growth of soft tissue and new bone formation in the patient's body.

[0021] In addition, a pore gradient of 200 μm to 900 μm or up to 2500 μm can be considered, where the pore gradient segments are 100 μm each. In addition, it can also be considered that the implant has a closed structure with a pore gradient exceeding 10 μm.

[0022] It is also advantageous if the ceramic base material (in the non-finished implant) is present in the form of powder or granular ceramic microparticles. Here, the particle shape affects the geometric and biological properties within the implant.

[0023] In addition, it is possible that the ceramic microparticles are arranged in a partially crystalline or crystalline form. Thus, a more durable and longer-lasting implant can be achieved.

[0024] A particular embodiment is characterized in that the ceramic microparticles and the metal microparticles are spherical, the corresponding particle size of the metal microparticles is 5 to 10 μm and the corresponding particle size of the ceramic microparticles is 25 to 120 μm, and / or the ceramic microparticles and the metal microparticles are cubic, the side length of the metal microparticles is 5 to 25 μm and the side length of the ceramic microparticles is 40 to 60 μm. In particular, a favorable bio-mechanical strength is ultimately achieved through a mixture of spherical and cubic microparticles.

[0025] In addition, it can be considered that the implant has a first layer of material (e.g., the outermost 0 to 30 layer of the implant), a last layer of material, and an intermediate layer of material (main layer), where the intermediate layer is surrounded by the first and last layers, and the first layer is solid, the intermediate layer is porous, and the last layer is solid or the first layer is porous, the intermediate layer is solid, and the last layer is porous.

[0026] Furthermore, it is appropriate if the implant is constructed to be hydrophobic or hydrophilic on different, in particular opposite, surfaces. This enables various different possibilities for the mechanical and physical interaction between the implant and the patient's body tissue. These tissue interactions can be influenced (enhanced or reduced) via the partial absorbability (Resorbierbarkeit) of certain structural or geometric parts of the implant.

[0027] Furthermore, it can be specified that the implant is produced by an additive manufacturing method. Implants processed using this method can be manufactured particularly economically.

[0028] Furthermore, the object of the present invention is achieved by a method for manufacturing the implant according to the present invention. Here, the method has the following steps, which are advantageously carried out successively and preferably in this order:

[0029] a) Mix a base material and a donor material, which is either in powder form, granular form, liquid form, or viscous form, into a raw mixture.

[0030] b) Combine the raw mixture - for example, by laser sintering - in a spatially resolved manner (preferably with different and gradually applied energy according to a single layer) into a plurality of single layers (for example, combining the raw mixture elements at determined positions to obtain a specific implant shape of the implant).

[0031] c) Stack the plurality of single layers and bond them layer by layer to form a finished implant.

[0032] The implant manufactured according to these steps has the advantages determined above.

[0033] By, for example, manufacturing the first material layer under the application of high energy, manufacturing the intermediate material layer under the application of low energy, and manufacturing the last material layer under the application of high energy, in this example, the center of the implant, that is, the intermediate material layer of the implant has more micropores than the first and last material layers, enabling them to be absorbed more quickly.

[0034] In other words, the present invention relates to a three-dimensional implant, which is produced by productive processing, wherein the implant, for example, has α-tricalcium phosphate (α-TCP), β-tricalcium phosphate (β-TCP), and hydroxyapatite (HA), as well as a mixture composed of β-TCP and HA, a so-called biphasic calcium phosphate (TCP), a bioactive glass component, and a mixture composed of α-TCP, β-TCP, and HA, ZrO 2 、AI 2 O 3 、β-SiAION, a biodegradable photopolymer, a composite material composed of ceramic and metal particle components. Here, ceramic particles or a composite material composed of ceramic powder and an organic polymer matrix or an inorganic composite material composed of ceramic absorbable or non-absorbable materials are combined with one or more metal particles or bioactive glass components in a spatially resolved manner under the application of energy. Through layer-by-layer connection and subsequent curing, by stacking and connecting many single layers, a three-dimensional implant with structurally determined macroscopic and microscopic porosities is formed.

[0035] Thus, it is possible to ensure the manufacture of the implant in a short time and to match the implant to the human structural region of the patient's body. By combining different porosities with an additive / productive manufacturing method, it is possible to form here a new, shape-related gradient geometry (formgebundene Gradientengeometrie) which can generate specific bioactivity through bioabsorption.

[0036] A pore size of about 600 μm allows rapid ingrowth of blood vessels, connective tissue and possibly bone tissue. Since the nutrient supply of important cells within the implant scaffold can only take place at a distance of 150 to 200 μm, especially by diffusion, the regeneration of blood vessels is a decisive process for the successful integration of the implant. Through the gradient design of the material composition and porosity and the implant-specific absorption characteristics of the implant, the nutrient supply of the biological tissue is optimized. At the same time, specific structures in the range of 300 to 500 μm and larger micropores in the range of 800 to 1,200 μm are formed. By means of a construction strategy, the micropores are distributed in a gradient manner, thus forming a gradient pattern which enables the largest possible porosity while optimizing the mechanical conditions.

[0037] Therefore, the implant according to the invention is either completely or at least partially absorbable. This enables optimal growth of soft tissue and new bone formation. This comprehensive blood vessel growth also helps to transport important anti-infection cells deep into the implant. Large implants or smaller implants with a structurally enlarged surface are particularly beneficial.

[0038] The growth of soft tissue additionally increases the strength of the implant, and the bioactivity of the implant is not controlled by growth factors, but jointly controlled by the geometry of the implant and the absorbable components, especially by the release of metal and non-metal ions. At the same time, metabolic and cytophysiological reactions (a chemical and physical reaction or process within a cell) are activated or favorably modified for the healing process.

[0039] Therefore, the implant according to the invention does not receive a coating / painting, but the bioactivity of the implant according to the invention is structurally inherent in this implant. Thus, the implant becomes more durable during installation, and the bioactivity of the implant is distributed over the entire time the implant is present in the patient's body.

[0040] In other words, the present invention thus relates to a manufactured, ceramic or partially ceramic implant with a complex geometry, having a three-dimensional and highly gradient, interconnected and / or partially interconnected open-cell structure. By gradually applying different energies to the respective material layers (for example, applying energies between 49.52 and 2971.20 mJ / cm 2 between, especially from 80 to 110 mJ / cm 2 , preferably from 150 to 200 mJ / cm 2 and particularly preferably from 260 to 290 mJ / cm 2 ), higher strength can be achieved. In addition, higher strength can also be achieved through different irradiation durations (between 1 and 60 seconds), irradiation intensities (5 to 49.52 mW / cm 2 ) and waiting times for each single layer of the implant. Here, a longer irradiation duration in the first and main material layers results in a higher strength of the implant.

[0041] In addition, implants manufactured in an additive manner obtain increased strength, different energy applications for each material layer, and the pore chains (Porenstrang) connected by connecting channels are irradiated to different degrees. After irradiation, the ceramic implant is then heat-treated (in temperature steps at intervals of 250 to 300 °C, 380 to 400 °C, 450 to 470 °C and 600 to 650 °C), without closing the micropores at the same time. In addition, the heat treatment results in an additional increase in strength, a structural transformation and changed surface properties of the implant. By different heat treatment methods (in temperature steps at intervals of 750 to 800 °C, 870 to 890 °C, 900 to 950 °C, 950 to 1050 °C, 1130 to 1170 °C, 1200 to 1300 °C and 1400 to 1450 °C), smooth surface properties can be achieved, where the implant is porous inside. The implant can be made of at least one or two or three or four of the aforementioned material components.

[0042] The absorbable part of the implant according to the invention can be between 0 and 100%, especially between 20 and 30% or between 45 and 50% or between 65 and 80%. The implant can be constructed from the outside in (from its outer layer to its inner layer) such that the outer material layer is mostly absorbable, and the absorbability of the material layer decreases continuously or discontinuously from the outer layer to the inner layer.

[0043] In addition, the implant of the present invention may have a special structure for fixation by means of bolts or fixing devices made of titanium, medical high-grade alloy steel, absorbable metal alloys, polymers, and absorbable polymer materials. The orientation of such a special structure extends at an angle between 5 to 28 degrees, 30 to 50 degrees, 55 to 75 degrees, and 80 to 85 degrees with respect to the implant surface. The fixation structure should have a wall thickness between 0.5 mm and 20.0 mm here.

[0044] In particular, it can be considered that the three-dimensional implant of the present invention is provided with notches or voids in the case of expansion using the implant of the present invention, especially dental implants (a method for autologous bone reconstruction using heterologous, allogeneic, or synthetic bone substitute materials). The purpose of these notches is to be able to fill autologous bone tissue or bone fragments (the patient's own bone tissue / bone fragments) during implantation (during the placement of the implant into the patient's body). These notches can have dimensions of, for example, 1.0 to 1.5 mm, 1.5 to 2.0 mm, 2.0 to 2.5 mm, or 2.5 to 2.8 mm. If larger bone fragments are to be placed into the implant, or if the implant is to absorb larger bone fragments, the implant can accordingly have a fixation structure with an enlarged geometry for receiving the respective bone fragments.

[0045] The materials used for the implant of the present invention are in powder, granular, and liquid or viscous mixture forms, and these materials are mixed with each other in different amounts and compositions. In this case, the particle shape is particularly important because the desired geometric and biological properties of the implant are adjusted by applying energy, and this applied energy depends on the powder and granular forms.

[0046] In this case, spherical microparticles with sizes of 5 to 18 μm and 25 to 120 μm can be used, where the metal component is less than the ceramic microparticles. In addition, the ceramic microparticles can have a completely or partially cubic shape with side lengths of 5 to 25 μm and 40 to 60 μm. Furthermore, the first component of the ceramic microparticles can contain a mixture of geometrically non-uniform powder microparticles and the ceramic component can have a crystalline or partially crystalline arrangement.

[0047] The implant of the present invention, which is structurally layered, has a gradual or stepwise decline (degradability), making it possible for the implant to grow specifically into the patient's body in a cell type-specific manner in view of cell migration (actively changing the position of cells or cell populations within the patient's tissue). In addition, such an implant beneficially contributes to the definite activation of cell physiological processes above and within the implant. Description of the Drawings

[0048] The embodiments of the implant of the present invention and the method for manufacturing the implant will be described in detail with reference to the accompanying drawings below.

[0049] In the accompanying drawings:

[0050] Figure 1 is a cross-sectional view of the implant of the present invention; and

[0051] Figure 2 is a flowchart depicting the steps of manufacturing the implant.

[0052] The accompanying drawings are merely schematic in nature and only assist in understanding the present invention. The embodiments are purely exemplary. Detailed Embodiments

[0053] Figure 1 An implant 1 is shown, which has a base material 2 and a donor material 3. The layered structure of the implant 1 can also be seen. Here, the material layers are arranged such that in this embodiment, the first material layer 4 is arranged at the bottom, the intermediate material layer 5 is located above the first material layer 4, and the last material layer 6 is arranged at the top (above the intermediate material layer 5) in this illustration. Here, the first, intermediate, and last material layers 4, 5, and 6 have different densities / porosities from each other.

[0054] Figure 2 A flowchart is shown, which depicts the various steps of obtaining the implant 1 of the present invention. In the first step S1, the ceramic base material 2 and the donor material 3 containing an absorbable component are mixed with each other to form a raw mixture RM. In the subsequent step S2, the components of this raw mixture RM are bonded to each other in a spatially resolved manner by laser sintering, thereby forming a plurality of single layers, such as the first single layer ES1, the second single layer ES2, and additional single layers, where an arbitrary single layer is denoted by ESn. In the third step S3 following step S2, these single layers ES1, ES2,..., ESn are stacked and bonded to each other under the application of energy, thereby obtaining the finished implant 1 as a product.

[0055] List of reference numerals

[0056] 1 Implant

[0057] 2 Base Material

[0058] 3 Donor Material

[0059] 4 First Material Layer

[0060] 5 Intermediate Material Layer

[0061] 6 Last Material Layer

[0062] ES1 First Single Layer

[0063] ES2 Second single layer

[0064] ESn nth (arbitrary) single layer

[0065] RM Raw mixture

[0066] S1 First step

[0067] S2 Second step

[0068] S3 Third step

Claims

1. An implant for implantation into a patient, the implant being manufactured using a productive manufacturing process and having an implant body that is at least partially absorbable and at least partially porous in regions, the implant body being composed of a ceramic base material provided with a donor material that releases ions for influencing the metabolism of the patient's cells in the implanted state, wherein, the donor material penetrates into the base material such that the donor material is present throughout the implant volume, wherein the implant has a first layer, a last layer, and intermediate layers, the intermediate layers being surrounded by the first layer and the last layer, and wherein the first layer, the intermediate layers, and the last layer have different densities / porosities from one another, wherein the donor material has ceramic microparticles and metal microparticles, at least some of the ceramic microparticles and the metal microparticles being cubic, the side length of the metal microparticles being 5 to 25 micrometers and the side length of the ceramic microparticles being 40 to 60 micrometers, and some of the ceramic microparticles and the metal microparticles being spherical, the particle size of the spherical metal microparticles being 5 to 18 μm and the particle size of the spherical ceramic microparticles being 25 to 120 μm, wherein the individual micropores in the implant body are interconnected via connecting channels, and wherein the donor material is arranged and concentrated in the base material such that the connecting channels are necessarily generated in the implant body when ions are released in the implanted state.

2. The implant according to claim 1, characterized in that: the implant body is divided into layers or partial regions of different densities and / or porosities.

3. The implant according to claim 1, characterized in that: the implant body has a total porosity between 3% and 60%.

4. The implant according to claim 1, characterized in that: the size of the micropores in the implant body is in the range of 300 μm to 1500 μm.

5. The implant according to claim 1, characterized in that: the ceramic base material is present in the form of powdered or granular ceramic microparticles.

6. The implant according to claim 1, characterized in that: the intermediate layers have more micropores than the first layer and the last layer.

7. The implant according to claim 6, characterized in that: the first layer and the last layer are solid.

8. A method for manufacturing an implant according to any one of claims 1-7, comprising the following steps: a) mixing a base material and a donor material into a raw mixture, b) combining the raw mixture in a spatially resolved manner into a plurality of single layers, and c) stacking the plurality of single layers and bonding them layer by layer into a finished implant body.

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