WO2022023405A1

WO2022023405A1 - Use, after sterilization, of a metal implant having a surface that is provided with pore openings, to produce an active ingredient-loaded metal implant

Info

Publication number: WO2022023405A1
Application number: PCT/EP2021/071118
Authority: WO
Inventors: Ralph Wilken; Dirk Salz; Uwe Specht; Kai BORCHERDING
Original assignee: Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung eingetragener Verein
Priority date: 2020-07-31
Filing date: 2021-07-28
Publication date: 2022-02-03
Also published as: DE102020120343A1; EP4188467A1

Abstract

Use, after sterilization, of a metal implant having a surface that is provided with pore openings, to produce an active ingredient-loaded metal implant, the metal implant having, after sterilization, a surface that is provided with pore openings having, at least when first loaded with the active ingredient, a capillary pressure for water of ≥ 1 hPa, preferably ≥ 5 hPa, more preferably ≥ 10 hPa.

Description

The present invention relates to the use of a metal implant with a surface covered with pore openings after sterilization for the production of a metal implant loaded with active substance, the metal implant with pore opening covering - Ter surface has a positive capillary pressure for water at least at the start of loading with the active substance. The invention also relates to a method for loading a metallic implant with a surface covered with pore openings with an active substance and a sterilized metallic implant with a surface covered with pore openings, which is particularly suitable for the use according to the invention and the method according to the invention. When inserting an implant into the human or animal body, the success of the implantation is regularly not only dependent on the design and composition of the implant, but on the one hand the avoidance of infections during the implantation or as a result of the implantation is just as important and on the other hand the integration of the implant into the recipient body. To this end, it is desirable to equip implants as flexibly as possible with active ingredients which bring about and/or support the desired effects, in particular avoiding infections and promoting integration of the implant into the recipient body. Active ingredients suitable for avoiding infections in this context are antibiotics, phages or other anti-infective substances up to cells, integration-supporting substances are, for example, active ingredients that promote osseointegration, growth factors, phosphates, silicates or other medically effective ones substances. It is of great importance to design the implants in such a way that they can be effectively loaded with the desired substances. For example, porous surfaces of implants are known in the prior art, which enable good osseointegration. To this end, there are various strategies with which implants are treated and/or manufactured in order to achieve the desired drug absorption capacity. Examples include: 1. Etching processes or oxidation processes that make the implant surface porous, 2. Additively manufactured implants or implants that have been superficially adapted using additive technologies, for example through Selective Laser Melting (SLM), Electron Beam Melting (EBM), Binderjet, etc. (ImplantCast, Stryker, Aesculap), which provide porosity in the design, 3. Layers by means of plasma spraying, for example hydroxylapatite, titanium, calcium phosphate (DOT, Medicoat), which on Generate porosity due to their structure, 4. Laser structures (product Laser-Lok from Camlog), which creates porosity in the surface. Furthermore, surfaces are disclosed which describe a receiving volume and which can be loaded with antibiotics. In addition to good osseointegration, these should enable local antibiosis, particularly in revision operations: 1. Laser structures (according to WO 2020/127594 A1)) 2. Porous layers with a release control layer (DE 102016204899 A1). Basically, there is a need to load the implants in situ, ie directly before or even during the implantation operation, with the active ingredients suitable for the respective application as flexibly as possible. As a rule, the active ingredients are provided in an aqueous medium for loading. This loading must be simple (can be carried out by specialist staff in the clinic), fast (can be implemented for the acute treatment of emergency patients as well as within the time frame of a planned therapy), reproducible (take up the same dose independently of the person doing it) and preferably without the use of therapeutic agents or auxiliary substances (eg solvents) which damage cells and tissue. The previous metallic porous implant surfaces do not allow reliable loading, especially after sterilization. Individual methods such as SLM produce a comparatively hydrophobic surface (contact angle > 90°), so that the penetration of a load with aqueous solutions into the implant is inhibited. Furthermore, the surface energy changes with age and the storage of the surface, so that the implant surface cannot be loaded sufficiently and not reproducibly. When metallic surfaces are stored, an adsorbate layer develops on metallic surfaces, which reduces the surface energy and changes the wetting behavior, in particular the wetting by aqueous media. This adsorbate layer that forms depends on the environment or the ambient air, so that the resulting wetting behavior of the implant surface varies greatly. Metallic implant surfaces made of titanium or stainless steel (316 L) are always covered with a layer of titanium dioxide or chromium oxide. Immediately after production, the implant surfaces have a high surface energy, because there are always hydroxide groups, especially on titanium oxide. These hydroxide groups react with each other or with components from the ambient air. This means that the titanium dioxide surface will have a water contact angle > 70° over time. Furthermore, it is possible for organic molecules from the ambient air to settle on the implant surface and render the surface hydrophobic. This effect can be observed particularly in packaging processes (heat sealing) and in sterilization processes. Sterilization is a process that completely kills off all germ-forming units (bacteria and their spores, fungi and their spores, and viruses). In comparison, the number of germ-forming units is only reduced by 10 ⁶ during disinfection. The person skilled in the art is particularly familiar with the following sterilization methods: For many implants, especially titanium implants, gamma sterilization is the preferred sterilization method. Co60 is used as the radiation source. After being sealed in packaging, the implant is irradiated with a dose of at least 25 kGy. The advantage of this method is that the implants can be stored and transported in sterile packaging. Implants that are not delivered sterile are sterilized in the hospital. Here, the method of steam sterilization is preferably used. Typically, the items to be sterilized or filled are heated in steam for 20 minutes to 121 °C at a pressure of two bars or for 5 minutes to 134 °C at 3 bars. To destroy prions, the mixture is heated to 134° C. at 3 bar for 18 minutes. Ethylene oxide sterilization is used for medical devices that cannot be sterilized by gamma or steam sterilization. This is the case with cardiac pacemakers, whose electronic components cannot withstand gamma radiation and, for example, with multi-lumen tubing that cannot withstand the temperature of steam sterilization. It plays a subordinate role for metallic implants. Plasma sterilization works with hydrogen peroxide as the working gas. The products to be sterilized come in a special packaging that is permeable to hydrogen peroxide, which guarantees that the product remains sterile after the plasma reactor has been opened. The method is not widely used and is commercially available under the name "Sterrad". Today, implants are often sterilized in blister packs made of polymeric materials. The very hard gamma radiation decomposes the polymers of the packaging material, particularly when the implants are not packaged evacuated, so that molecular fragments are found on the implant surface. This makes the surface highly hydrophobic (contact angle >90°). The other usual sterilization processes (superheated steam sterilization, hydrogen peroxide sterilization with and without plasma phase, low-temperature steam and formaldehyde sterilization or ethylene oxide sterilization) also interact with the implant surface and change it in terms of wettability and internal absorption capacity. These hydrophobic surfaces are state-of-the-art (eg manufacturer Camlog / DOT / Implantcast / Stryker), especially when it comes to titanium implants. Table 1 shows the atomic composition of a titanium implant with a SiO _x coating directly after production, stored in air and variously gamma sterilized (25 kGy). Table 1: Atomic composition of a SiOx surface of a coated implant after different treatment methods.

In addition to the increase in carbon content in the gamma-sterilized samples, the oxidation state of the nitrogen is important. In the gamma-sterilized sample, it is in the positive oxidation state and not, as in the other samples, as an amino compound in the negative oxidation state. The fact that porous implants from the prior art have hitherto regularly had relatively hydrophobic surfaces or, at least depending on the storage and/or sterilization conditions, have repeatedly had surface conditions that are negative for loading, has kept experts from considering these implants as for a (subsequent), in particular an in situ, loading with the desired active substances. Against this background, it was also the object of the present invention to provide a possibility by means of which implants can be reliably loaded with active substances even after sterilization. The loading processes should preferably take place quickly. This object is achieved by using a metallic implant with a surface covered with pore openings after sterilization for producing an active substance-loaded metallic implant, the metallic implant with a surface covered with pore openings having a capillary pressure of ≧1 hPa, at least at the start of loading with the active substance ≥ 5 hPa, preferably ≥ 10 hPa for water. A surface covered with pore openings within the meaning of the present invention is a surface that includes openings that create a connection between the area surrounding the implant and one or more spaces that are below the implant surface (inside the implant). In the context of the present invention, it is not necessary for the entire surface of the implant to be covered with pore openings; it can also be useful to provide only specific areas of the implant with corresponding pore openings and the pores underneath. A pore within the meaning of the present application is a cavity in a solid material with at least one opening to the environment of the material. In order to ensure good fillability, pores within the meaning of this application are preferably open-pored, ie many pores form an open-pored material in that the majority of the pores have at least two openings to an adjacent pore or to the implant surface. The pores can be channel-like, spherical or sharp-edged. The open-pored material is preferably located as a layer on the surface of the implant. The shape of the pores is determined by the pore walls and the openings. There is always an opening if there is a minimal opening cross-section when cutting through the pore layer by layer. In order to find the minimum opening cross-section, the cuts may have to be made in all spatial directions. In case of doubt, the capillary pressure for water is measured as specified below. It is to the credit of the present invention to specify a parameter, namely a corresponding capillary pressure, which makes an implant appear suitable for loading with an aqueous active substance solution or aqueous active substance dispersion. It has been found that the capillary pressure depends on essential properties of the area of the implant to be used according to the invention that is provided for the absorption of the active ingredient. The capillary pressure is determined thermodynamically and is dependent on the equation in the (simplified) case of a tube

σ: OF energy of the liquid (mN/m) Θ: contact angle r: capillary radius (mm) The positive capillary pressure for water in the sterilized metallic implants to be used according to the invention can be ensured by various measures. Preferred within the meaning of the present invention is a use in which the sterilized metallic implant with pores is configured at least before loading (i) in such a way that, even after storage for 180 days under atmospheric conditions and 23° C., it has a capillary pressure of ≧1 hPa, preferably ≧5 hPa, more preferably ≧10 hPa for water or (ii) a restored capillary pressure of ≧5 hPa, preferably ≧10 hPa for water or (iii) a capillary pressure produced by a specific process of ≧5 hPa, preferably ≧10 hPa, more preferably ≧15 hPa for water. Variant (i) of the preferred use according to the invention is ultimately a material property and structural property that characterizes the implant in that it maintains its capillarity to water to a minimum even under certain circumstances, here during storage. In the context of the present invention, in case of doubt, storage takes place in germ-proof, preferably non-evacuated packaging made of film, material A117A; Aluminum polyethylene composite material from Gruber-Folien GmbH & Co. KG, Straubing. It is also possible, within the meaning of variant (ii) of the preferred use according to the invention, to restore a capillary pressure that was originally present, for example by using a targeted purification process to remove adsorbates, such as carbon-containing adsorbates, in order to reduce the corresponding capillary pressure for water and to ensure that the use according to the invention can be ensured. In addition to classic bath-assisted wet-chemical processes (e.g. aqueous cleaning, aqueous pickling processes, ultrasonic cleaning, solvent cleaning, vapor degreasing), dry processes such as plasma processes both at low pressure and at atmospheric pressure, UV radiation, particularly for titanium-containing implant surfaces, Vacuum UV irradiation, laser processes, flame treatment, ozone in question. As a further possibility, it is possible, in the sense of variant (iii) of the preferred use according to the invention, to generate the desired capillary pressure for the implant according to the invention via a post-processing step (a specific method). A specific method within the meaning of the present invention is such a method step which is intended in particular to produce the desired capillary pressure and which can be differentiated from the production of the pores. Such steps could be, for example, an etching process to enlarge the pores, a coating process that improves the wettability of the pore surfaces, or any method that effects the configuration and/or surface properties of the pores after their creation. A sterilized metallic implant is preferred for the purposes of the present use, which preferably comprises one or more of the following metals on its surface, optionally without considering a coating to increase the capillary pressure with respect to water, selected from the group consisting of titanium, Aluminum, Vanadium, Iron, Chromium, Molybdenum, Manganese, Nickel, Cobalt, Tantalum, Zirconium, Tin, Niobium, Zinc, Magnesium, Tungsten, Copper, Silver, Gold, Platinum, Palladium, Rhodium. It is preferred that the pore layer (beneath the surface of the implant covered with pore openings) is designed in the sense of an open-pore foam. In this context, open-pored means—as already indicated above—that the majority of the pores have more than one opening, so that cavities are provided that can be formed from a number of interconnected pores and even channels. It is important for many applications within the meaning of the present invention that there is not only a sufficiently high capillary pressure with respect to water for the fundamental possibility of loading the metallic implant to be used according to the invention, but that loading is also preferably desired to take place relatively quickly. While the capillary pressure is essentially a thermodynamic quantity, the loading rate represents a kinetic quantity. The Washburn equation describes the path of a liquid in a porous medium (uniaxial horizontal expansion):

with L: propagation length σ: surface energy of the liquid r: capillary radius t: time Θ: contact angle η: viscosity of the liquid to achieve fast loading speed, the radius should be as large as possible. Against this background, a use according to the invention is preferred, in which case the implant after sterilization with complete wetting of the upper surface covered with pore openings surface with water within ≦300 s, preferably ≦10 s, more preferably ≦1 s, particularly preferably ≦100 ms and very particularly preferably ≦10 ms, a filling with water of 90% of the volume that can be filled with water is achieved. These high filling speeds ensure that, in the use according to the invention, in situ loading of active substance is also possible, for example during an operation. The propagation coefficient κ (see measurement example 4.1) is defined by

L(t): length of propagation at time t L(0): length of propagation at time t=0 t: contact time A use according to the invention is preferred, wherein the coefficient of propagation κ in at least one spatial direction within the implant after sterilization is ≧50 mm ² /s ≧100 mm ² /s, more preferably ≧200 mm ² /s, more preferably ≧500 mm ² /s, more preferably ≧700 mm ² /s, more preferably ≧1000 mm ² /s and particularly preferably ≧1500 mm ² /s s is. The mass increase coefficient µ _w (see measurement example 4.2) is defined by:

w(t): mass at time tw(0): mass at time t=0 t: contact time Alternatively or additionally preferred is a use according to the invention, wherein the mass increase coefficient µ _w in at least one spatial direction within the implant tes after sterilization ≧50 mg ² /s, preferably ≧100 mg ² /s, preferably ≧200 mg ² /s, preferably ≧500 mg ² /s, preferably ≧700 mg ² /s, preferably ≧1000 mg ² /s s and more preferably ≥ 1500 mg ² /s. Both coefficients κ and µ _w are individually but also jointly an expression of structural properties of the porous layer of the implant. A high κ can be generated, for example, by primarily having trench structures in the porous layer, with the trench structures preferably being arranged parallel to one another, while the respective (available) pore volume plays an important role for the increase in mass in addition to a corresponding structuring . For the measurement of the measurands κ and µ _w , reference is made to the measurement examples below. According to the invention, preference is given to a use in which, after sterilization, the implant has a volume of ≧0.1 μL/cm ² , preferably ≧0.3 μL/cm ² , more preferably ≧1 μL/cm ² , which can be filled by wetting with water at the start of loading , more preferably ≧3 μL/cm ² , particularly preferably ≧10 μL/cm ² based on the surface of the implant covered with pore openings, preferably based on the entire surface of the implant. It has been found that suitable measures (cf. also below) can be used to provide implants to be used according to the invention which have a good absorption volume for active ingredients in aqueous solutions or aqueous dispersions. The volume that can be filled with water is a parameter for this. To determine the volume that can be filled with water, reference is also made to below. As already indicated above, the sterilization procedure is of great importance for the usability of an implant in the sense of the present invention. This applies in general and also to the preferred embodiments. A number of sterilization methods lead to hydrophobic treatment of the implant surface, so that the sterilized implant is not sufficiently suitable for in situ loading with aqueous active substance solutions. In principle, however, it is surprising that it is possible for a person skilled in the art to find appropriate sterilization methods, depending on the configuration, which ensure sufficient capillarity—in the sense of the present invention—for the implant. In addition, however, the invention fundamentally provides the person skilled in the art with further possibilities, even with a sterilization method in which an excessive loss of capillarity can occur, of maintaining the implant in a loadable state. It is quite surprising that, for certain post-treatment steps can ensure sufficient capillarity despite less suitable sterilization methods, while on the other hand it is possible by suitable measures to restore a capillarity required in the sense of the present invention even after sterilization. Preference is given to a use according to the invention, in which the metallic implant after sterilization in the area of the surface covered with pore openings has a static water contact angle Θ ≤ 80 °, preferably ≤ 60 °, more preferably ≤ 30 °, ≤ 15 °, ≤ 10 ° and particularly preferably ≤ 5 ° has. For the purposes of the present invention, the static water contact angle between the material of the implant on the surface and the loading medium is crucial for easy-to-achieve loading success within the meaning of the present inventive use: A static water contact angle of ≥ 90 ° would result in the loading medium could not penetrate into the capillaries without further measures. It would only be possible to generate the corresponding filling of the cavities/capillaries via an external pressure. This is very disadvantageous, particularly in the case of time-sensitive loading processes, such as those that take place in situ during an operation. Within the scope of our own research, it surprisingly turned out that the ratio between the mean radius of the pores and cosine Θ is of particular importance for the loading capacity of the metallic implants to be used in the application according to the invention. Accordingly, a use according to the invention is preferred, with the quotient r/cos(Θ) being 5 μm-200 μm, with r=average radius of the respective narrowest pore point of the pore below the surface covered by a pore opening and Θ=static contact angle. To determine the mean radius, reference is made to the description below. In order to ensure the properties of the implant to be used according to the invention that are desired for the use according to the invention, the following measures are particularly suitable: An effective approach to setting a high capillary pressure for water in the area of the surface covered with pore openings of the implant to be used according to the invention is to provide the pores in the form of trench structures with an area coverage of ≧95% based on the surface covered with pore openings. The surface covered with pore openings in the sense of this text is generally that part of the surface of the implant that has pore openings. Only those surface parts are included that have at least 10 pore openings per mm², preferably at least 100 pore openings per mm² and more preferably at least 400 pore openings per mm², with the measurement area under consideration always being one mm². When setting the trench structures (with overlap), it must be taken into account that trench openings that are too large or too long lead to a capillary blockage and thus limit the possible capillary pressure. Open trenches generally result in only a low capillary pressure being produced, while largely closed trenches lead to a high capillary pressure. In this context, reference is also made to the examples. A further variant, which can also be used if necessary, for setting the desired properties is in particular the influencing of the static contact angle Θ by means of a suitable coating. A use according to the invention is correspondingly preferred, in which case a hydrophilicity-increasing coating is present in the area of the pore-covered surface. Increasing hydrophilicity in the sense of the present invention is a separately applied coating (after production of the pores), which increases the hydrophilicity compared to the uncoated variant. In order to achieve an improved hydrophilic surface, in particular in the case of titanium surfaces, two methods are preferred, on the one hand the coating of the titanium surface, in particular the outer titanium surface, preferably deposited from the gas phase. Surprisingly, the outer coating already helps to improve the penetration of water into the cavities/pores without significantly changing the surface chemistry of the cavities/pores. Without being bound to a theory, the coating, especially in the opening areas of the pores/cavities, means that the hydrophobic opening areas of the pores lose their effect as a capillary barrier and the liquid medium can thus enter areas of higher capillarity and thus develop the suction effect . Coatings based on silicon oxides (SiOx), polyalkylene oxide, in particular polyethylene oxide (PEO), polyvinyl alcohol, polyacrylates, carbohydrates, mucins, hydrogels and hydroxylapatite are preferred here. The application of such layers by means of plasma polymerisation, plasma-enhanced chemical vapor deposition (PECVD), metal-organic chemical vapor deposition (MOCVD) or physical vapor deposition (PVD), eg sputtering, evaporation, in particular electron beam evaporation, is particularly preferred. On the other hand, the implant surface can be coated from the liquid phase, in particular by means of dip coating in a solution mixed with a coating material. After drying, the pores / cavities are provided with a thin (preferably < 1 µm) thick layer of the coating material. The following substances in particular are suitable as coating material: carbohydrates, in particular glucose, fructose, galactose, mucins; PPO-PEO block copolymers (poloxamers), polysorbates, sorbitan esters (such as sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan tristearate, sorbitan monooleate), phospholipids, hydrophilic natural or synthetic polymers such as e.g. B. alginate, dextran, chitosan, carrageenan, polyethylene glycol (PEG), soluble polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), carboxymethyl cellulose (CMC), HES (hydroxyethyl starch). Hydrogel-forming polymers can be obtained by a polymerization or a polyaddition or polycondensation containing at least one of the substances from the following group: polymerized hydroxyethyl methacrylate (HEMA), polymerized hydroxypropyl methacrylate (HPMA), polymerized α-methacryloyl -ω-Methoxypolyethylene glycol, polymerized methacryloyloxyethylphosphorylcholine (MPC), polyethylene glycol bisacrylate and their copolymers, crosslinked resorbable pre-polymers of the type ABCBA with commercially sold examples Focalseal® (Genzyme) or Advaseal® (Ethicon) with A = acrylic or methacrylic group, B=hydrolytically divisible group, the polymers of lactide, glycolide, 2-hydroxybutanoic acid, 2-hydroxyvaleric acid, trimethylene carbonate, polyorthoester, polyanhydrides, polyphosphates, polyphosphazenes and/or polyamides and/or copolymers thereof, and C= hydrophilic polymers, in particular polyethylene glycol (PEG), Polyvinylalcohol (PVA), polyvinylpyrrolidone (PVP), poly(N-isopropylacrylamide) (PNi-PAAM) or sol-gel systems. It is particularly preferred that the coating has good solubility, in particular good solubility in water. The coating is removed during the loading procedure. For this purpose, attention is paid to the molecular weight, particularly in the case of polymer coating materials. Molecular weights <5000 g/mol are preferred. A further variant with which the hydrophilicity of the surface can be improved for the purposes of the present invention is irradiation of the surface covered with pore openings with high-energy radiation, in particular in the UV spectral range with wavelengths between 100 nm and 380 nm. In a further embodiment Irradiation with wavelengths of up to 700 nm is advantageous, especially if titanium surfaces contain other foreign elements in addition to titanium and oxygen. Here, too, there is an effect similar to that of the hydrophilic coating: the hydrophobic opening areas acting as a capillary barrier are rendered hydrophilic (eg via a photocatalytic effect), so that the medium can enter the area of higher capillarity. A similar effect can be achieved by plasma treatments or treatment with ozone, preferably in combination with high-energy radiation, in particular in the UV spectral range with wavelengths between 200 nm and 380 nm. Accordingly, a use according to the invention is preferred, in which case the production or restoration of the capillary pressure (particularly after sterilization) takes place at least in part by increasing the hydrophilicity through irradiation and/or plasma treatment and/or ozone. Another very effective starting point is to design the pore production in such a way that nanopores are provided at least on part of the pore walls of the pores with the main volume (micropores). Accordingly, a use is preferred according to the invention in which the pores below the surface covered with pore openings include both nanopores with a pore radius r _nano of 5 nm-100 nm and micropores with a pore radius r _micro of 5 μm-500 μm. In order to enable both good thermodynamic wetting properties and good wetting speeds, the combination of porosity on different size scales is advantageous: The porosity on small scales increases the capillary pressure (5 nm ≤ r _nano ≤ 100 nm). Due to the porosity on large scales, the flow resistance is reduced. (5 µm ≤ r _micro ≤ 500 µm). The porosity ratio is preferably: r _micro /r _nano ≧10. In order to keep the flow resistance low, preferably only the pore surfaces of the large-scale porosity are covered with a thin layer of small-scale porosity. The layer thickness of the layer of small-scale porosity is preferably ≦1/10*r _micro . In case of doubt, the procedure for determining the pore boundaries and the pore radii is as follows: A cross section through the pore-containing layer of the substrate to be used according to the invention is prepared perpendicularly to the surface. The pore spaces are filled with a suitable embedding compound, eg an epoxy embedding compound, so that all cavities are filled with the appropriate material, even if no opening to the surface (pore opening) is visible in the section. The further procedure is explained in more detail with reference to FIG. 1: FIG. 1 schematically shows a cross-sectional section through the pore area of an implant to be used according to the invention ; (2) District that has only smaller neighboring districts in the immediate vicinity; (3) substrate; (4) Circle that has at least one smaller and at least one larger circle as neighbors in the immediate vicinity; (5) lower limit of cover layer; (6) pore space; (7) pore opening. Procedure (schematic): 1. A circle is drawn at each point of the pore area in such a way that the circle touches the pore wall at at least one point but does not intersect it. 2. All circles that touch the pore wall at only one point are discarded and not considered further (not shown). 3. All circles that have at least one smaller and at the same time at least one larger circle as neighbors in the immediate vicinity are again discarded (4 in Figure 1). 4. The connection of the two points of contact of circles (1 in Figure 1), which only have larger neighboring circles in the immediate vicinity, form the pore transition or the pore opening. 5. The radius of the circles (2 in Figure 1), which only have smaller neighboring circles in the immediate vicinity, is the respective pore radius. To determine r _micro and r _nano , two groups of pore radii are formed, namely the group of pore radii ≥ 1 µm and the group of pore radii < 1 µm. The radius of the micropores r _micro is the arithmetic mean of the group of pore radii ≥ 1 µm. The radius of the nanopores r _nano is the arithmetic mean of the group of pore radii < 1 µm. Part of the invention is also a method for loading a sterilized metallic implant with a pore-covered surface with an active substance, comprising the steps: a1) providing a sterilized metallic implant with a pore-opening-covered surface, as defined above, variant (i), preferably in an embodiment defined in more detail above or a2) providing a sterilized metallic implant with a surface covered with pore openings, as defined above, variant (ii) or (iii), preferably in an embodiment defined in more detail above, b) at least in the case a2) Establishing or restoring the capillary pressure, as defined above, and c) contacting the implant at least in the region of the surface covered with the pore openings with a preferably aqueous solution or aqueous dispersion of the active substance. By means of the method according to the invention it is effectively possible to load sterilized implants with a surface covered with pore openings quickly and reliably with a desired active substance (in particular in an aqueous solution or aqueous dispersion). Part of the invention is also a sterilized metallic implant with a surface covered with pore openings, the implant having a capillary pressure of ≧1 hPa, preferably ≧5 hPa, more preferably ≧10 hPa after storage for 180 days under atmospheric conditions and 23° C for water. The sterilized metallic implant according to the invention with pores on the surface is preferably configured as defined in more detail above. Also preferred according to the invention is a sterilized implant according to the invention, the propagation coefficient κ in at least one spatial direction within the implant being ≧50 mm ² /s, preferably ≧100 mm ² /s, more preferably ≧200 mm ² /s ≧500 mm ² /s, preferably ≧700 mm ² /s, preferably ≧1000 mm ² /s and more preferably ≧1500 mm ² /s and/or wherein the mass increase coefficient _μw in at least one spatial direction within the implant is ≧ 50 mg ² /s, preferably ≧100 mg ² /s, preferably ≧200 mg ² /s, preferably ≧500 mg ² /s, preferably ≧700 mg ² /s, preferably ≧1000 mg ² /s and more preferably ≧1500 mg ² /s. These metallic implants according to the invention are particularly well suited for the use according to the invention or the method according to the invention. The invention is explained in more detail below using examples. Measurement examples and implementation examples: In case of doubt, the measurement examples are the variant with which a variable in the sense of the present text is determined. 1. Measurement of the capillary pressure by means of a rise experiment: A metal strip that is 1 cm wide and 30 cm is provided with a porous structure. The sample is immersed in the center of a glass vessel filled to 1 cm with demineralized water. The height of rise is determined in equilibrium (with the lid closed). The capillary pressure P _Κ can be determined from the rise height h according to P _Κ = ρ ∙ g ∙ h with ρ: density of the liquid g: gravitational acceleration 20 cm correspond to ~ 20 hPa 2. Measurement of the capillary pressure using a top-down cell (procedure to be used in case of doubt) : A three-dimensional implant with a porous surface structure is placed on a placement cell according to FIG. The pressures are read before placement and after equilibration of the pressure conditions with the implant placed. The capillary pressure is obtained by forming the difference. FIG. 2 shows the measuring arrangement schematically with: 1 container that is as stiff as possible (e.g. metal pipe) 3 Test medium (here water) 5 Seal, eg O-ring 7 Pressure gauge attached gas-tight to the vessel 9 Structured metal surface, can also be 3D-shaped 11 Knurled screw to increase the water column 13 Connection pipe to the pressure gauge and the knurled screw. A V2A steel tube with an internal diameter of 5 mm and an external diameter of 7 mm and a length of approx. 1 m is used for the pressure measuring cell (1). A digital pressure gauge DPI 104 from the manufacturer General Electric is used as the manometer (7). The manometer measures pressures between 0 and 700 mbar with an accuracy of 0.05% FS including non-linearity, hysteresis, repeatability and temperature effects from 14 °F to 122 °F (-10 °C to 50 °C). The display updates twice per second. The measuring cell is filled with water (3), the sample (9) is placed on the O-ring (5). The air gap between the structured metal surface and the water surface in the metal tube and the O-ring is then filled with water by raising the water column using the knurled screw (11). The initial pressure initially increases to p _start [mbar]. As soon as the water column comes into contact with the porous metal surface, the pressure in the system drops. The pressure drop is then observed until a saturation value pmin is reached and the pressure that can be read fluctuates by less than 0.01 mbar per 3 seconds. The sample (9) is then pulled off the surface so that the pressure rises again to p _end . The capillary pressure is determined from the differential pressure, the minimum pressure p _min and the pressure after lifting the substrate p _end . 3. Measurement of the accessible pore volume using a Wilhelmy balance: Use of the Wilhelmy balance DCAT25 from Dataphysics Use of a sample with surface porosity, sample size: 2 cm×2 cm—immersing the sample so that there is contact with the water. - The Wilhelmy balance automatically brings the samples into contact with the water surface and measures the time-resolved increase in mass. If the sample is completely wetted, a mass saturation value Ms (in mg) is set. This depends on the area of the sample Ap (in cm²), on the pore volume per area MVA (in µl/cm²) and on systematic measurement errors Merr (in mg) that are independent of the surface area, such as the sample buoyancy due to partial water immersion. Ms(Ap) = Merr +MVA ∙ Ap The measurement of the saturation masses Ms of two samples of different lengths, with the same width and thickness, which have the same contact surfaces to the water, without being bound to a theory also the same systematic error Merr . The difference in the saturation mass divided by the difference in area Ap1-Ap2 of the samples gives the embedded mass in the pore volume per area MVA. The quotient of the MVA and the density of the water (1g/cm³) gives the pore volume per area. - Measurement of weight gain after complete filling / wetting of the pores - Reference of weight gain to the wetted / filled area. The accessible pore volume can be determined by considering the density of the water, taking into account the increase in mass. 4.1. Measurement of the filling as a function of the contact time: Use of a sample with surface porosity, sample size: 2 cm x 2 cm Depositing a drop of water with a defined volume on the sample surface, which is aligned as horizontally as possible. Video recording from above onto the sample surface (viewing direction parallel to the surface normal) of the wetting process parallel to the sample surface. Determination of the propagation length L(t) depending on the contact time t. The propagation length L(t) plotted over time results in a surface-specific curve. The parameters of the non-linear function can be determined by means of a regression calculation

L(t): Propagation length at time t L(0): Propagation length at time t=0 t: Determine the contact time that results in the temporal behavior of the wetting length. L(t) is the propagation length as a function of the contact time t, κ is the propagation coefficient in mm²/s and L(0) is the droplet radius in mm at the measuring time t equal to zero. The adjustment calculation takes place within the time interval t = 0 s up to the contact time t _inter , until the propagation length reaches L _inter = 2/3 [L _max – L(0)] + L(0). L _max is the maximum propagation length measured (saturation value) and L(0) is the minimum propagation length at time t = 0. The measuring interval of the contact time t between t =0s and t _inter should ideally consist of at least 8 evenly distributed measuring points. There are surfaces, for example, with parallel channels, which have a preferred direction of propagation in the surface plane, so that longer propagation lengths are covered in the same contact times than in other directions on the sample. Therefore, surfaces can have different propagation coefficients κ. 4.2. Kinetic measurement using a Wilhelmy balance: Use of the Wilhelmy balance DCAT25 from Dataphysics Use of a sample with surface porosity Immersing the sample so that there is contact with the water. - The Wilhelmy balance automatically brings the samples into contact with the water surface and measures the time-resolved increase in mass until the sample is saturated, or the equilibrium state of capillary pressure, atmospheric pressure and hydrostatic pressure. - The mass w(t) plotted over the contact time t results in a surface-specific curve. The parameters of the non-linear function can be determined by means of a regression calculation

- w(t): mass at time t - w(0): mass at time t=0 - t: determine the contact time, which results in the temporal behavior of the mass increase. Here µ _w is the mass increase coefficient in g²/s and w(0) is the initial mass in g at the measurement time t equal to zero. The compensating calculation takes place within the time interval t = 0 s up to the point in time up to the contact point in time t _inter , until the mass reaches w _inter = 2/3 [w _max – w(0)] + w(0). Here, wmax is the maximum measured mass (saturation value) and w(0) is the mass at time t = 0. The measuring interval of the contact time t between t =0s and t _inter should ideally consist of at least 8 evenly distributed measuring points. There are surfaces, for example, with parallel channels, which have a preferred direction of propagation in the surface plane, so that longer propagation lengths are covered in the same contact times than in other directions on the sample. Therefore, surfaces can have different mass increase coefficients _µw . 5. Determination of the static water contact angle Θ In case of doubt, the water contact angle is determined according to DIN EN ISO 19403-2 6. Performing gamma sterilization and sealing with evacuation Co60 is used as the radiation source. The gamma sterilization was carried out by BGS Beta-Gamma-Service GmbH & Co. KG in Wiehl with a dose of 25 kGy. The samples to be sterilized are sealed in a vacuum in a PE bag (packaging material: packaging bag, Gruber foil material A117A; aluminum-polyethylene composite material, Gruber-Folien GmbH & Co. KG, Straubing) and gamma-sterilized. 7. Performing gamma sterilization and sealing without evacuation Co60 is used as the radiation source. The gamma sterilization was carried out by BGS Beta-Gamma-Service GmbH & Co. KG in Wiehl with a dose of 25 kGy. The samples to be sterilized are sealed in a PE bag (packaging material: packaging bag, Gruber foil material A117A; aluminum-polyethylene composite material, Gruber-Folien GmbH & Co. KG, Straubing) and gamma-sterilized without evacuation. In general, the following applies: In exemplary embodiments 6 and 7, the samples to be sterilized can also be wrapped in aluminum foil. Even a simple wrapping brings slight improvements in terms of maintaining capillarity. Exemplary embodiments: Exemplary embodiment 1: Laser structure (L29) Description of production/storage Material: Ti6Al4V flat substrate (supplier: ARA-T Advance GmbH, D-46539 Dinslaken) Laser: 100 W Nd:YAG laser (type CL100 from CleanLaser, Herzogenrath, Germany with Stamp optics and f(330) f-theta lens Emitted wavelength: 1064 nm Energy distribution in the laser spot: Gauss spot diameter in focus: approx. 107 µm Target power: 100% (100 W) Pulse repetition frequency: 100 kHz Pulse length: 130 ns Laser fluence on the substrate: 10.5 J/cm2 Number of consecutive laser pulses per position: 26 Number of repetitions of the complete laser treatment (number of cycles): 1 Feed between the individual laser positions: 0.065 mm Line spacing: 0.160 mm Scanning speed was 10000 mm/s. The measurements according to measurement examples 1, 2 and 3 were carried out within 48 hours after the samples were produced. The capillary pressure was measured according to measurement example 1: Sample geometry: 50 mm x 300 mm x 1 mm Treated area: strips 10 mm x 300 mm on one side of the sheet: The laser treatment was performed line by line along the longitudinal direction of the sheet metal. The height of rise from the water surface, determined using a ruler, is 23 cm. This corresponds to a capillary pressure of ~ 23 mbar. Measurement of the capillary pressure according to measurement example 2: Sample geometry: 20 mm x 130 mm x 1 mm Treated area: 20 mm x 130 mm over the entire area on one side: The laser treatment took place scanning line by line along the longitudinal direction of the sheet. The minimum pressure of the top-down cell set in after 2400 seconds, with the cell pressure dropping by less than 0.03 mbar/s. The minimum pressure was p _min = 61 mbar. After detaching the sample, the pressure in the attachment cell rose to p _end = 90 mbar. The difference in pressure results in a capillary pressure of 29 mbar for surface treatment with L29. After gamma sterilization according to example 6, the capillary pressure measured according to the measurement example was 225 mbar. If, on the other hand, the gamma sterilization was carried out according to example 7, the capillary pressure measured according to the measurement example was 20 mbar. Measurement of the pore volume according to measurement example 3 after sterilization according to implementation example 6: Sample geometry: 1 cm x 4 cm and 1 cm x 8 cm, treated with the laser on both sides with Ap1 = 8 cm² and Ap2 = 16 cm². The Wilhelmy measurement gives a value of Ms = 280 mg for the saturated mass of the samples with Ap = 16 cm². For the samples with Ap = 8 cm², Ms = 244 mg. The difference in the saturated masses divided by the difference in the areas and the density of the water gives a pore volume per area of 5 µl/cm². Measurement of the propagation kinetics according to measurement example 4 after sterilization according to implementation example 6: Test setup: - high-speed camera: Photron NOVA S6800k 16GB; 10,000 fps - Pipette: 1 – 10 µl, Eppendorf - 10 µl demineralized water - Titanium substrate: 2 x 2 cm², laser-treated on one side with parameter L29 The high-speed video was processed using the public domain image processing programs VLC-Mediaplayer and ImageJ, the propagation lengths L( t) determined in different propagation directions from the center of the applied water droplet at different times t. The measured values were plotted using the Origin Pro V9.7 software and the propagation coefficient was determined by means of a fitting calculation. For L29, this is κ = 2000 mm²/s with a residual of 0.98 in the direction with the fastest propagation. On the surface perpendicular to the fastest direction of propagation, the slowest propagation occurs with a κ = 240 mm²/s with a residue of 0.72 Measurement of the mass absorption kinetics according to measurement example 4.2 after sterilization according to example 6: Sample geometry: A sample L29, 1 cm x 8 cm , treated with the laser on both sides, parallel to the longitudinal axis of the sample as described above. A second sample L29_quer, 1 cm×4 cm, was banded with the laser perpendicular to the longitudinal axis. The increase in mass at the different points in time t was determined using a Wilhelmy scale. The measured values were plotted using the Origin Pro V9.7 software and the mass increase coefficient µ _w was determined by means of a fitting calculation. For L29, this is µ _w = 2000 mg²/s with a residual of 0.97 for the direction with the fastest propagation. If the surface is wetted along the slowest propagation, µ _w = 2 mg²/s results with a residual of 0.91. Exemplary embodiment 2a: Laser structure (L2) Description of production/storage Material: Ti6Al4V flat substrate (supplier: ARA-T Advance GmbH, D-46539 Dinslaken) Laser: 100W Nd:YAG laser (type CL100 from CleanLaser, Herzogenrath, Germany land with stamp optics and f(330) f-theta lens Emitted wavelength: 1064 nm Energy distribution in the laser spot: Gauss Spot diameter in the focus: approx. 107 µm Target power: 100% (100 W) Pulse repetition frequency: 200 kHz Pulse length: 200 ns Laser fluence on the substrate: 5.3 J/cm2 Number of consecutive laser pulses per position: 20 Number of repetitions of the complete laser treatment (number of cycles): 1 Feed between each laser position: 0.053mm Line spacing: 0.107mm Scan speed was 10000mm/s. The first measurement according to measurement example 1 was carried out within 48 hours after the samples were produced. The capillary pressure was measured according to measurement example 1: Sample geometry: 50 mm x 300 mm x 1 mm Treated area: strips 10 mm x 300 mm on one side of the Sheet metal: The laser treatment was carried out line by line along the longitudinal direction of the sheet metal. The rise height from the water surface, determined using a ruler, is 18 cm. This corresponds to a capillary pressure of ~ 18 mbar. Measurement of the propagation kinetics according to measurement example 4.1: Experimental setup: - High-speed camera: Photron NOVA S6800k 16GB; 10,000 fps - Pipette: 1 - 10 µl, Eppendorf - 10 µl demineralized water - Titanium substrate: 2 x 2 cm², laser-treated on one side with parameter L2 From the high-speed video, the propagation lengths L(t) from the center of the applied water drop at different points in time t were determined using the public domain image processing programs VLC-Mediaplayer and ImageJ. The measured values were plotted using the Origin Pro V9.7 software and the propagation coefficient was determined using a fitting calculation. For L2, this is κ = 1300 mm²/s with a residual of 0.98 for in the direction with the fastest propagation. Perpendicular to the surface to the fastest propagation, the slowest propagation results with a κ = 130 mm²/s with a residual of 0.3. Measurement of the capillary pressure according to measurement example 2: Sample geometry: 20 mm x 130 mm x 1 mm Treated area: 20 mm x 130 mm over the entire area on one side: The laser treatment took place scanning line by line along the longitudinal direction of the sheet. The minimum pressure of the top-down cell set in after 1600 seconds, with the cell pressure dropping by less than 0.03 mbar/s. The minimum pressure was p _min = 71 mbar. After detaching the sample, the pressure in the attachment cell rose to p _end = 91 mbar. The difference in pressure results in a capillary pressure of 20 mbar for the surface treatment with L2. This value was reduced to 14 mbar by sterilization according to example 6 and to 0 mbar according to example 7. Exemplary embodiment 2b Laser structure (L2 after gamma sterilization and storage) The sample from exemplary embodiment 2a was gamma sterilized according to exemplary embodiment 6. The measurement according to measurement examples 1 and 2 was carried out after storage for 180 days at room temperature. Measurement of the capillary pressure according to measurement example 1: The rise height from the water surface determined using a ruler is 0.3 cm. Penetration of water into the cavities after contact with water was not observed. Measurement of the capillary pressure according to measurement example 2: The capillary pressure determined using the attachment cell according to measurement example 2 is 0.5 mbar. Penetration of water into the cavities after contact with water was not observed. Example 3: Laser structure (L2) + pppolyacrylic acid Description of the production Laser structure Material: Ti6Al4V flat substrate (supplier: ARA-T Advance GmbH, D-46539 Dinslaken) Laser: 100W Nd:YAG laser (type CL100 from CleanLaser, Herzogenrath, Germany - land with stamp optics and f(330) f-theta lens Emitted wavelength: 1064 nm Energy distribution in the laser spot: Gauss Spot diameter in focus: approx. 107 µm Target power: 100% (100 W) Pulse repetition frequency: 200 kHz Pulse length: 200 ns laser fluence at the substrate: 5.3 J/cm2 Number of consecutive laser pulses per position: 20 Number of repetitions of the complete laser treatment (number of cycles): 1 Advance between the individual laser positions: 0.053 mm Line spacing: 0.107 mm Scanning speed was 10000 mm/s. Description Deposition of the acrylic acid layers The plasma polymer acrylic acid layers (ppAA) are produced with the help of the plasma polymerisation of acrylic acid at low pressure. For this purpose, a 360 l plasma reactor is evacuated to a base pressure of 5*10-3 mbar and then enough acrylic acid vapor is let into the reactor that a pressure of 0.03 mbar is established. A high-frequency plasma (13.56 MHz) is ignited using a plasma electrode (35 x 35 cm) placed 7 cm above the chamber floor. The samples to be coated (silicon wafers and laser-structured titanium substrates) are attached to a stainless steel plate 7 cm above the plasma electrode. After a process time of 160 s, the following layer thicknesses and contact angles were measured on the silicon wafer. In addition, the layer thickness was measured on the silicon wafer after a brief period of water storage (approx. 10 s).

Table 2: Properties of ppAA layers depending on the plasma power

The lasered Ti sample with stable polyacrylic acid (175 W) was gamma sterilized according to Example 7 and stored for 2 years. After the storage period, a capillary pressure of 19 mbar was detected. These hydrophilic and water-insoluble layers have the disadvantage that they remain on the implant and are therefore also implanted. Alternatives are hydrophilic ppAA layers, which completely dissolve in water after a short storage time (max. 5 minutes). This means that the surface is hydrophilic during loading with an antibiotic solution and the implant used does not have a ppAA coating on the surface. Thus, the complex question of the biological properties of the ppAA surface does not apply. The water-soluble layer is produced with a plasma power ≤ 125 W. After gamma sterilization according to Example 7 and 180 days of storage, a capillary pressure of 20 mbar was detected in each case. Exemplary embodiment 4: Laser structure (steel -LPC) Description of production/storage Material: stainless steel samples (AISI 316L; WNr.1.4404) flat substrate laser: 100W Nd:YAG laser (type CL100 from CleanLaser, Herzogenrath, Germany with stamp optics and f(330) f-theta lens Emitted wavelength: 1064 nm Energy distribution in the laser spot: Gauss Spot diameter in focus: approx. 107 µm Target power: 100% (100 W) Pulse repetition frequency: 100 kHz Pulse length: 130 ns Laser fluence on the substrate: 10 .5 J/cm2 Number of consecutive laser pulses per position: 20 Number of repetitions of the complete laser treatment (number of cycles): 1 Feed between the individual laser positions: 0.065 mm Line spacing: 0.240 mm Scanning speed was 10000 mm/s. The measurement took place within 48 h after the samples were stored and examined at a room temperature of 20 – 25 °C and a humidity of 20 – 25 % rh Measurement of the capillary pressure according to measurement examples 1 and 2 Sample geometry: 50 mm×300 mm×1 mm Treated area: Strips 10 mm×300 mm on one side of the sheet: The laser treatment was carried out scanning lines along the longitudinal direction of the sheet. The sample is immersed in the center of a glass vessel filled to 1 cm with demineralized water. The height of rise is determined in equilibrium (with the lid closed). The rise height from the water surface, determined using a ruler, is 16 cm. This corresponds to a capillary pressure of ~ 16 mbar. According to measurement example 2, a capillary pressure of 17 mbar could be determined with a top-down cell. After superheated steam sterilization according to DIN EN 285:2016-05, the capillary pressure measured according to the measurement example was 215.5 mbar. Exemplary embodiment 5 Detection of micro- and nanoporosity L2 and L29: Material: Ti6Al4V flat substrate (supplier: ARA-T Advance GmbH, D-46539 Dinslaken) Laser treatment analogous to exemplary embodiment 1 for the laser parameter L29 and exemplary embodiment 2a for L2 for pores > 10 µm, the pore radii were examined using metallographic sections and light microscopy as described above. Porosities < 10 µm were examined using scanning electron microscopy (SEM) or transmission electron microscopy (TEM) on a Tecnai F20 S-TWIN microscope. The laser treatment with L2 leads to the formation of interconnecting pores in the form of channels on the sample surface. The average radius r _micro of these pores is 35 µm. This porosity is covered with a 150 nm thick porous titanium oxide layer of smaller porosity, the average pore radius r _nano of which is 10 nm. The laser treatment with L29 leads to the formation of interconnecting pores in the form of channels on the sample surface. The mean radius r _micro of these pores is 50 µm. This porosity is covered with a 300 nm thick titanium oxide layer of smaller porosity, the mean pore diameter r _nano of which is 25 nm. A gamma sterilization according to example 6 and example 7 did not change the pore geometry of either L29 or L2. Exemplary embodiment 6: Laser structures (after sterilization and storage) Material: Ti6Al4V flat substrate (supplier: ARA-T Advance GmbH, D-46539 Dinslaken) Sample geometry: 50 mm x 300 mm x 1 mm Laser-treated area: strips 10 mm x 300 mm on a Side of the sheet Laser treatment analogous to example 1 for the laser parameter L29 and analogous to example 2a for the laser parameter L2 The samples, sterilized according to example 6, were stored for 180 days. It turns out that sample L2 does not have good storage stability for 180 days. After storage, the capillary pressure measured according to the measurement example was 20 mbar. Sample L29, on the other hand, has good storage stability for 180 days. After 180 days of storage in a laboratory atmosphere, the capillary pressure for L29 is 220 mbar, measured according to the measurement example. Example 7 Laser Structures Hydrophilization or Restoration of the Hydrophilicity The test specimens from example 2a and gamma sterilization according to example 7 and storage for 180 days were subjected to the following plasma treatments. low pressure plasma treatment. The specimens were fixed near the HF (13.56 MHz) operated cathode. After the rectangular low-pressure reactor with a volume of 360 l and an installed suction capacity of 4500 m³/h to a pressure less than 0.02 mbar, the oxygen was admitted into the reactor at a flow rate of 280 sccm. A self-bias voltage of 250 V was set on the test specimens with the aid of a high-frequency plasma discharge (13.56 MHz). The duration of the treatment was 5 minutes. After the system had been ventilated, the specimens were removed and tested. Atmospheric pressure plasma treatment: Atmospheric pressure plasma treatment was carried out using an atmospheric pressure plasma system (PFW10) from Plasmatreat, Steinhagen. The compressed air plasma burned at a transformer discharge voltage of 300 V. The compressed air was supplied at 30 l/min. A single plasma nozzle was used, which meandered over the sample in the longitudinal direction at a distance of 6 mm between the substrate and the nozzle head in three treatment cycles at a speed of 5 m/min in 4 mm increments. Measurement after low-pressure plasma treatment: L2 after gamma sterilization according to Example 7, 180 days of storage and low-pressure plasma treatment: the water rise height is 12.5 cm. This corresponds to a capillary pressure of ~ 12.5 mbar. The capillary pressure measured according to measurement example 2 is 14 mbar. Measurement according to atmospheric pressure plasma: L2 after gamma sterilization according to example 7 and atmospheric pressure plasma: the water rise height is 16 cm. This corresponds to a capillary pressure of ~ 16 mbar. The capillary pressure measured according to measurement example 2 is 18 mbar. Exemplary embodiment 8: cellulose cloth (not to be used according to the invention) Description of the production/storage Measurement of the capillary pressure according to measurement example 1: Material: paper filter (manufacturer: Whatman), folded, Grade 2V, diameter 320 mm, pore size 8.0 μm (smoothed) Sample geometry: 10 mm x 300 mm The height of rise from the water surface, determined using a ruler, is 11.5 cm. This corresponds to a capillary pressure of ~ 11.5 mbar. Measurement of the propagation kinetics according to measurement example 4.1: Material: Kimwipe KIMTECH SCIENCE* precision wipes, 19 g/m² Test setup: - High-speed camera: Photron NOVA S6800k 16GB; 10,000 fps - Pipette: 1 – 10 µl, Eppendorf - 10 µl demineralized water From the high-speed video, the propagation lengths L(t) in different propagation directions from the center of the applied water drop to different certain points in time t. The measured values were plotted using the Origin Pro V9.7 software and the propagation coefficient was determined using a fitting calculation. This is κ = 12 mm²/s with a residual of 0.85. Measurement of the mass uptake kinetics according to measurement example 4.2: Material: paper filter (manufacturer: Whatman), folded, Grade 2V, diameter 320 mm, pore size 8.0 µm (smoothed) Sample geometry: 10 mm x 40 mm Using a Wilhelmy balance, the mass increase at the different times t definitely. The measured values were plotted using the Origin Pro V9.7 software and the propagation coefficient µ _w was determined by means of a fitting calculation. For the filter paper, this is µ _w = 8.6 mg²/s with a residue of 0.92.

Claims

Claims: 1. Use of a metallic implant with a surface covered with pore openings for the production of an active substance-loaded metallic implant, wherein the metallic implant with a surface covered with pore openings after sterilization has a capillary pressure of ≥ 1 hPa, preferably ≥ 5, at least at the start of loading with the active substance hPa, preferably ≧10 hPa for water. 2. Use according to claim 1, wherein the metallic implant after sterilization with pores at least before loading (i) is designed such that it has a capillary pressure of ≥ 1 hPa, preferably ≥, even after storage of 180 days under atmospheric conditions and 23 ° C 5 hPa, more preferably ≧10 hPa for water or (ii) a restored capillary pressure of ≧5 hPa, preferably ≧10 hPa for water or (iii) a capillary pressure of ≧5 hPa, preferably ≧, produced by a targeted method 10 hPa, preferably ≧15 hPa for water. 3. Use according to claim 1 or 2, wherein the implant after sterilization with complete wetting of the surface covered with pore openings with water within 300 s, preferably 10 s, more preferably 1 s, particularly preferably 100 ms and very particularly preferably 10 ms a filling with water of 90% of the volume that can be filled with water is achieved. 4. Use according to one of the preceding claims, wherein the propagation coefficient κ in at least one spatial direction within the implant after sterilization is ≥ 50 mm ² /s, preferably ≥ 100 mm ² /s, more preferably ≥ 200 mm ² /s, more preferably ≧500 mm ² /s, more preferably ≧700 mm ² /s, more preferably ≧1000 mm ² /s and particularly preferably ≧1500 mm ² /s. 5. Use according to one of the preceding claims, wherein the mass increase coefficient µ _w in at least one spatial direction within the implant after sterilization is ≥ 50 mg ² /s, preferably ≥ 100 mg ² /s, preferably ≥ 200 mg ² /s, preferably ≧500 mg ² /s, preferably ≧700 mg ² /s, preferably ≧1000 mg ² /s and more preferably ≧1500 mg ² /s. 6. Use according to one of the preceding claims, wherein the implant, after sterilization, at the start of loading, has a volume that can be filled by wetting with water of ≧0.1 μL/cm ² , preferably ≧0.3 μL/cm ² , more preferably ≧1 μL/cm ² , particularly preferably ≧3 μL/cm ² based on the surface of the implant covered with pore openings related to the entire surface of the implant. 7. Use according to one of the preceding claims, wherein the metallic implant after sterilization in the area of the surface covered with pore openings has a static water contact angle Θ≦80°, preferably ≦60°, more preferably ≦30°, ≦15°, ≦10° and more preferably ≤ 5°. 8. Use according to one of the preceding claims, wherein the quotient r/cos(Θ) is 5 μm-200 μm, with r=mean radius of the respective narrowest pore point of the pore below the surface occupied by the pore openings and Θ=static contact angle. 9. Use according to one of the preceding claims, wherein a hydrophilicity-increasing coating is present in the area of the surface covered with pore openings. 10. Use according to one of the preceding claims, wherein the pores below the surface covered with pore openings include both nanopores with a pore radius r _nano of 5 nm - 100 nm and micropores with a pore radius r _micro of 5 μm - 500 μm. 11. Use according to one of the preceding claims, wherein the production or the restoration of the capillary pressure takes place at least in part by increasing the hydrophilicity by means of irradiation and/or plasma treatment and/or ozone. 12. A method for loading a sterilized metal implant with a surface covered with pore openings with an active substance, comprising the steps of: a1) providing a sterilized metal implant with a surface covered with pore openings, as defined in claim 2, variant (i), preferably in one of the configurations defined in more detail in claims 2 to 11 or a2) providing a sterilized metallic implant with a surface covered with pore openings, as defined in claim 2, variant (ii) or (iii), preferably in one of the configurations defined in more detail in claims 3 to 11, b) at least in case a2) Production or restoration of the capillary pressure, as defined in claim 1, and c) contacting the implant at least in the area of the surface covered with pore openings with a preferably aqueous solution or aqueous dispersion of the active substance. 13. Sterilized metallic implant with a surface covered with pore openings, the implant having a capillary pressure of ≧1 hPa, preferably ≧5 hPa, more preferably ≧10 hPa for water after storage for 180 days under atmospheric conditions and 23°C. 14. Sterilized metal implant with pores on the surface according to claim 13, in the configuration according to the definition in one of claims 2 to 11. 15. Sterilized metal implant according to claim 13 or 14, wherein the propagation coefficient κ in at least one spatial direction within of the implant ≧50 mm ² /s, preferably ≧100 mm ² /s, more preferably ≧200 mm ² /s, more preferably ≧500 mm ² /s, preferably ≧700 mm ² /s, preferably ≧1000 mm ² /s , and more preferably ≧1500 mm ² /s and/or wherein the mass increase coefficient _μw in at least one spatial direction within the implant is ≧50 mg ² /s, preferably ≧100 mg ² /s, preferably ≧200 mg ² /s , preferably ≧500 mg ² /s, preferably ≧700 mg ² /s, preferably ≧1000 mg ² /s and more preferably ≧1500 mg ² /s.