WO2014063816A1

WO2014063816A1 - Percutaneous implant and method for producing such an implant

Info

Publication number: WO2014063816A1
Application number: PCT/EP2013/003194
Authority: WO
Inventors: Michael Meyer; Richard Skiera
Original assignee: Otto Bock Healthcare Products Gmbh
Priority date: 2012-10-26
Filing date: 2013-10-24
Publication date: 2014-05-01
Also published as: DE102012021003B4; DE102012021003A1

Abstract

The invention relates to a percutaneous implant (1) that has an extracorporeal region and an intracorporeal region (600, 700) as well as a contact region (730) in which skin tissue (10) enters in contact with the implant (1). In said contact region (730), the surface has a porous structure with interconnecting pores (2), the size of the pores being smaller than 1 μm.

Description

Percutaneous implant and method of making such an implant

The invention relates to a percutaneous implant having an extracorporeal region and an intracorporeal region and a contact region, in which skin tissue comes into contact with the implant and there in particular with the surface of the implant, and a method for producing such an implant.

Implants may be in contact with both hard tissue, such as bone, and soft tissue, such as connective tissue or skin tissue. Depending on the application, there is a more or less pronounced interaction between the implant and the tissue. Medically, fibrous encapsulation in particular is considered disadvantageous. Most implant surfaces are designed to prevent encapsulation and seek integration through a well-designed regeneration tissue. In this case, cell-adherent integration is desired. An example of this is long-term implantable, percutaneous or transcutaneous implants.

Percutaneous implants, regardless of whether they are anchored in the soft tissue or bone, represent a discontinuity of the skin and thus of the epidermis. Thus, the barrier function of the epidermis against biological external influences, such as bacteria, viruses, fungi and other environmental influences such as sweat, cleaning mit - Contaminations or, for example Dirt or the like weakened or canceled. Via the so-called 3-phase line, at which the extracorporeal environment, the implant and the biological tissue meet, pathogens can enter the body and cause spontaneous or delayed foreign body reactions, for example superficial to deeper inflammations or infections. Another foreign body reaction or phenomenon of wound healing is the endeavor of the body or the skin to end the discontinuity of the skin penetration and encapsulate or repel the contact area or the implant. Thus, many models of skin conduction, a deep growth of the epidermis, also called Marsupialization.

In few cases, however, no deep growth occurs, but due to fibrous deposits, connective tissue-like cuffs are formed on the skin, which also

CONFIRMATION COPY outgrow extracorporeal. Thus, the formation of a gap and thus also relative movements between the tissue and the implant surface are always possible. This situation may also promote deeper infections in the area of skin penetration.

The prior art discloses a large number of implants that are implanted for a long time and in contact with soft or hard tissue. In tumor dop- rothetics, textiles are used to attach the connective tissue to the prosthesis and to stabilize muscles, allowing only indirect binding of the tissue. Such a textile may be formed as a tubular and cover the endoprosthesis over large areas. The fixed muscle and connective tissue encapsulates the textile, but finds no firm connection to the modified prosthesis surfaces. Associated with this, relative movements between the implant and the tissue can occur and prevent vascularization in the vicinity of the implant. It creates scar tissue or a fibrous encapsulation, a normal blood flow near the implant is then no longer guaranteed.

Even implants with a skin penetration are in contact with soft tissue. They are used to transmit mechanical loads, substances or electrical signals. For example, load-bearing, osseously anchored, percutaneous implants for attaching exoprostheses to the human body, for anchoring dental prostheses or for fixing bone segments to an external support structure (external fixator for osteosynthesis) are used. For the passage of substances or electrical signals implants such as catheters or cannulas are used with a variety of residence time.

Various solutions for shaping skin passages and the fixation or integration of soft tissue are known from the prior art. Of particular importance is the application of load-bearing, bone-anchored, percutaneous implants for long-term implantation. For long-term implantation, the requirements for integration into the tissue and anatomical structures are the most demanding. DE 80 89 74 C1 describes a prosthesis fastening device with a fastening rod which is inserted directly into the extremity skeleton. The fixation rod is inserted into the marrow sheath of the bone and fixed there, the exoprosthesis is releasably connected to the passing through the skin attachment rod. The design of the skin passage is not described.

US Pat. No. 4,143,426 A describes the permanent connection of artificial limbs with the aid of a load-bearing implant anchored in the long bones. Formulation requirements for the penetration of the skin are formulated and it is pointed out that in the contact area of the skin penetration tissue adhesion and the ingrowth of tissue are of great importance for the prevention of infections and the maintenance of the barrier function of the skin. Attention is drawn to the use of foamed or textile materials, in particular to the use of suede fibers.

WO 2005/055858 AI describes a skin passage of a osseär anchored dental implant, which should achieve an adhesion of the oral mucosa through an implant surface with pores of a mean diameter of less than Ι μηι. This porous surface produced by anodic oxidation should be advantageous for the Weichgewebeanbindung, by the very small pore size, penetration of bacteria is prevented, at least not promoted.

DE 103 53 400 AI describes a realization of a skin passageway with a load-bearing, ossär anchored implant in which the skin tissue in the area of the skin passage no fixation is provided, but the immobilization of the soft tissue is ensured by a fixation in macroscopic porous structures of deeper soft tissue structures ,

DE 103 57 579 B4, EP 382515 A2, US 2006/0041318 A1 and WO 02/38083 A1 describe constructive elements for the fixation of soft tissue. These are structures such as cuffs, hooks, nets or nonwovens, which fused with the subcutaneous tissue, the so-called subcutis, so that there is a mechanical relief on the 3-phase line. Even the sole use of soft Tissue anchors on or under the skin can lead to long-term infections.

A solution against Marsupialisation is described in DE 101 000 69 Cl, in which a material on the skin passage of intracorporeal, extracorporeal is pulled, so that colonizing germs and bacteria are pulled out of the body. An increase in the material at the skin passage is not provided.

US 2003/0171825 A1 describes the physiological and physical adhesion behavior of cells and bacteria with regard to hydrophobicity or hydrophilicity. A hydrophobic, extracorporeal surface makes the adhesion behavior more difficult so that the formation of biofilms can be reduced. Intracorporeal hydrophilic surfaces are arranged. EP 1 481 696 A1 describes a method for producing an implant with a bioactive, strontium-substituted, ceramic apatite coating. For this purpose, the implant to be coated is immersed in a solution of strontium, calcium and phosphate ions. At a pH of 5 to 8 and at a temperature of 30 ° C and 50 ° C an apatite coating should be carried out with substituted strontium ions. A porous surface is not achieved in this process.

WO 2008/074175 Al describes a strontium-rich apatite coating, which is realized via an anodic oxidation. As a result, an improved adhesion is to be achieved.

WO 03/039609 A1 describes a method for coating implants, in which a layer which optionally comprises several layers is applied to a titanium substrate by melting the surface by means of an applied direct current. Then, a topcoat is applied by immersing the implant in a solution of vesicles having an inner layer of phospholipid and an outer layer of calcium phosphate, again depositing on the implant while applying an electrical potential. A porous surface is not produced thereby. WO 2002/087648 A1 describes improved cell adhesion by coating an implant with titanium oxide and / or silicon oxide. With the help of the sol-gel technique, titanium oxide layers or composites of titanium dioxide and silicon dioxide with pores between 1 and 50 nm can be produced. These surfaces show an increased number of OH groups, to which, for example, the cell adhesion promoting proteins can be coupled.

EP 0 642 362 B1 states that the sol-gel method can be used to supply bioactive, inorganic substances which improve cell adhesion. In analogy to the skin penetration on the tooth, US Pat. No. 5,035,711A describes the advantageous effect of hydroxyapatite on skin penetration. Monolithic ceramics, made of calcium phosphates, were used. US 2003/0171825 A1 also describes the use of hydroxylapatites in the area of contact to the soft tissue, also in combination with biopolymers such as laminin and fibronectin, and a porous surface topography which is intended to enable soft tissue ingrowth. The pore structure is closed.

DE 101 58 302 A2 also describes the preparation of a coating of implantable and percutaneous metal bodies with calcium phosphate by means of an electrochemical method. In this case, the metal body is pretreated with NaOH or Ca (OH) _{2 in} order to achieve the improvement of the adhesive strength. However, the method does not allow a pore structure of the coating.

AT 44 13 78 E relates to osseointegrated implants, for example a dental implant with a nanostructure and a microstructure for improved growth of the surfaces in the bone. The pore structure is closed.

US 2007/0071788 A1 describes a percutaneous skin passage for anchoring exoprostheses with a skin connection on or in the implant in that the skin tissue grows into an open-pored macrostructure. In addition, antibacterial substances such as silver are used to counteract infection. US 2010-00249784 A1 describes a biocompatible polymer and ceramic coating for a percutaneous abutment in the craniofacial area of application, which has a porosity at the skin passage and is coated with active ingredients in a polymer or ceramic matrix. The pore structure is closed.

US 2010/0193363 A1 describes a method for forming a nano-open-pore structure on titanium surfaces, which is carried out by a basic etching with sodium hydroxide. An electrical connection is provided so that the basically known process is accelerated. The method describes the preparation of a net-like nanostructure without, however, using bioactive or antibacterial chemical additives for skin penetration. A more extensive bioactive coating with hydroxyapatite and other adhesion-promoting elements such as magnesium is not provided here. US 6,183,255 A describes an application for dental implants and orthopedic implants of such an etched surface.

DE 10 2008 054 403 A1 describes a nanostructure on the order of 1 nm to 1000 nm for improved cell attachment to implant surfaces. The structure is not interconnecting.

AT 501 408 A1 describes a coupling of proteins such as laminin or enterin, which are coupled to special, functionalized surfaces, for example diamond coatings.

CA 2476841 A1 describes metallic implants with collagen or chitosan coatings which lead to improved healing and at the same time have an antibacterial effect. US 2010/0286776 A1 describes the antibacterial effect of silver ions and their compounds on the skin penetration of hearing aid implants. There are also possible combinations with antibiotic agents. The object of the present invention is to provide an implant which provides a mechanical relief of an optionally osseointegrated anchoring and a better attachment to the soft tissue, in particular to the skin and an improved skin penetration. Furthermore, it is an object of the invention to specify a method for producing a suitable implant and / or an implant surface.

According to the invention this object is achieved by a percutaneous implant having the features of the main claim and a method for producing such an implant according to the features of the independent claim, advantageous refinements and developments of the inventions are listed in the dependent claims, the description and the figures.

The percutaneous implant with an extracorporeal area and an intracorporeal area and a contact area in which the skin tissue comes into contact with the implant provides that in the contact area the surface has a porous structure with interconnecting pores, wherein the pores are smaller than 1 μm is. While the interaction between the implant and the biological tissue takes place on the cellular level in the microscopic range, ie with a pore size between 1 μm and 1 mm, in the case of a porous structure with an average pore size in the nanobar region, ie between 1 nm and 1000 nm to detect an interaction of the biological tissue with the implant on a macromolecular or biomolecular level. The preferred mean pore size is in a range between 50nm and 100nm. After the introduction of the implant into the organism, an interaction between the implant and the biological tissue is produced by the nanostructured, open-pored surface. Due to the open-pore, preferably nanoporous surface of hydroxyapatite of the contact area, especially during wound healing, proteins, in particular native anchor proteins, collagens and other fibrous components, can penetrate from an extracellular matrix into the surface and act as a holding apparatus or as a new native, autologous surface. Associated with this is given an improved adhesion of the cells to the implant surface, and micro-relative movements can be reduced or avoided. An encapsulation of the implant is also reduced, resulting in improved blood flow the biological tissue, ie the skin tissue, and thus an increased immune compatibility at the implant surface are given in the contact area.

The contact region may comprise a calcium phosphate coating and / or an apatite coating, in particular a fluorohydroxil or hydroxylapatite coating. Particularly preferred is a pore structure of hydroxyapatite, optionally with substitution apatites such as fluoro, strontium or Karbonathydroxy- lapatite. Advantageously, the nanoporous interconnecting hydroxylapatite layer, in particular in the contact area in which the skin is to grow, is additionally provided or coated with cell adhesion-promoting additives of alkali metals and / or alkaline earth metals, in particular magnesium, strontium, sodium and potassium or a mixture of at least two of these Elements. Due to the fact that the epithelial cells and the connective tissue can grow due to the nanoporous interconnecting structure and the material used, the deep growth of the epidermis is reduced and possibly prevented. In the area of skin contact, a surface coating is thus provided which ensures optimal growth of the skin. Advantageously, the contact area comprises a calcium phosphate and / or an apatite coating, in particular a fluorohydroxil or hydroxyapatite coating. The calcium phosphate or apatite coating in the contact region with an open-pored structure, ie in which the pores are interconnected, has the advantage that improved adhesion of the tissue to the implant surface takes place.

Bacterial adhesion depends, among other things, on pore size, and it has been found that a reduced bacterial accumulation occurs in the case of a nanoporous interconnecting pore structure. The contact region may contain antibacterial additives, in particular silver, copper, magnesium or zinc or a mixture of at least two of these elements or their salts. As a result, bacterial adhesion and biofilm formation are reduced, suppressed or avoided. In one development of the invention, it is provided that the pore size in the contact region decreases in the distal direction, that is to say that there is a graduated distribution of the pore size at which the porosity in the intracorporeal extracorporeal direction decreases, ie the pore size is reduced. Due to the increasingly smooth, in the further extent compressed surface in the region of the 3-phase line or the transition of the skin tissue to the implant, the attachment of bacteria or the like is avoided or at least hindered.

The entire intracorporeal area of the implant may have a surface like the contact area with the coating described above.

At least one soft tissue anchor may be arranged on the implant in the intracorporeal region in order to support a positive connection of the soft tissue to the implant. The soft tissue anchor (s) are advantageously arranged immediately proximal to the region of permanent contact of the skin tissue with the implant. The soft tissue anchors can have a surface with a nanoporous structure with interconnecting pores, as has already been described in connection with the coating in the contact region. As soft tissue anchors, macrostructures, preferably with breakthroughs, e.g. Holes of 500 μπι diameter can be used. These macrostructures may be part of the implant substrate or may extend in the shape of a dish substantially perpendicular to the direction of skin penetration into the tissue. In the case of a surface design likewise having an open-pored, porous structure according to the invention in the nanobar region, a reduction or avoidance of fibrous encapsulation or scar formation should take place.

For use in osseointegrated implants, it is provided that means for anchoring in a bone in the intracorporeal area are arranged. This anchoring device or anchoring devices can be formed integrally with the contact region or, due to a modular construction of the implant, attached to the implant region with the contact region, for example screwed on. The anchoring device in this case has form-locking elements, for example a thread or conventional screw receptacles or bone anchors, which can be fixed in or on the bone. The surface of the anchoring device or the anchoring devices may also have a nanoporous structure with interconnecting pores. The bone cells can grow on the surface of the anchoring device, resulting in a stable anchoring of the implant within the bone.

At the distal end of the extracorporeal region of the implant receiving means for connection elements are formed, for example, for epitheses, medical device or prosthetic components. The implant preferably consists of titanium, a titanium alloy or a titanium material, preferably as a carrier of a surface coating, for example the nanoporous calcium phosphate or apatite coating according to the invention.

In addition to the nanostructure of the surface, a microstructure can be formed in the intracorporeal region which is deep between 2 μm and 500 μm, whereby the depth can decrease in the distal direction. For example, the microstructure may be made by chemical, physical, machining, or remodeling to form an increased surface area and to form multiple anchor positions for adherent cells. Furthermore, plasma spray coatings with particles in μηι size or order sintering can be made to form a corresponding structure. Likewise, particle beams or laser structuring can be used to produce a corresponding structure, optionally a 3D structure. This microstructure is carried out before the surface modification according to the invention.

The nanoporous surface structure is both in the contact area and in the intracorporeal region of the implant or the Weichgewebeanker is preferably thinner than 20 μηι, preferably thinner than 5 μηι, particularly preferably thinner than 2 μηι. Furthermore, the contact region and / or the intracorporeal region can be provided with a resorbable, preferably antibacterial cover layer. For this purpose, polymers, preferably antibacterial, biodegradable polymers may be provided as a cover layer. In particular, resorbable polymers such as Polylactide be provided with and without the above substances as a topcoat. This means that the cover layer is on the nanoporous and interconnecting coating and covers it. The cover layer may also be made of ceramic, biopolymer or metallic materials. One possibility for a resorbable cover layer consists in a metallic layer, in particular magnesium.

For further cell adhesion enhancement, the contact area and / or the intracorporeal area can additionally be chemically or physically functionalized. Also, in the fields, organic substances such as growth factors and / or pharmaceutical substances such as antibiotics, e.g. Tetracycline and / or antiseptics may be provided, which are deposited in or on the porous structure. Preference is given to proteins, integrins, laminin, fibronectin, collagen, fibrin, peptides, in particular RGD peptides, amino acids, chitosan and chitin.

The porous structure may be provided with wound healing and / or antibacterial agents, for example, coated or infiltrated. As an active ingredient, for example tetracycline into consideration. The extracorporeal area is advantageously designed as a polished surface, wherein the base body advantageously consists of titanium. The surface of the extracorporeal components may be provided with antibacterial substances or elements, for example copper, silver, fluorine, hydrophobic coatings such as PTFE, DLC or titanium nitrite.

The erfmdungsgemäße method for producing an implant, as described above, provides that etched at least in the contact area provided with a calcium phosphate surface of titanium or a titanium alloy, for example, with a strong base, preferably a NaOH solution, and the implant then with a calcium phosphate layer, then hydrothermally converted into an apatite and then thermally treated. According to the invention, the preparation of the coating takes place in several steps, while the apatite, in particular the hydroxyapatite in its chemical composition and in its pore size by Variation of the process parameters are changed.

By means of a strong sodium hydroxide liquor, preferably a 5M NaOH solution, the surface of the support, which may be composed of titanium or its alloys, is converted into an amorphous sodium titanate layer having a reticulated nanostructure. To prepare the nanoporous structure, the gelatinous and amorphous sodium titanate layer may be rinsed several times in deionized water.

To apply the calcium phosphate layer, the coating can be deposited on the etched titanium surface with an electrical voltage slightly below the electrolysis voltage present in the system in such a way that a nanoprotic and interconnecting, calcium phosphate-rich surface is formed, optionally with desired metallic additives. The optimum coating voltage is preferably 10% below the respective electrolysis voltage. The electrolytic solution consists of a dissolved calcium phosphate in a pH range between 3.5 and 4.5, preferably 4. The amounts of the additives in the calcium phosphate-rich electrolyte solution yield the later portion of the metallic substances such as zinc, copper, silver, sodium, potassium, Magnesium and / or substitution apatites such as strontium apatite, fluorapatite and / or carbonate apatite in the apatite coating. Over the duration of the coating, the mean pore size of the coating can be adjusted according to the invention. The duration is between 1 to 10 minutes, preferably 2 minutes.

Layer gradients may also be induced by an electric field orientation or by a controlled, e.g. continuous withdrawal of the implant from the electrolyte can be adjusted during the electrochemical deposition. This may be particularly advantageous for the area of skin penetration when the porosity decreases distally on the 3-phase line and is preferably completely closed extracorporeally.

In a further step, the calcium phosphate-rich coating, optionally with the proportions of the other metals provided hydrothermally in an alkaline solution, preferably Ca (OH) ₂ solution, at temperatures above 100 ° C and pressures above lbar, preferably at 150 ° C and 5 bar, converted into hydroxyapatite.

The annealing or thermal treatment of the hydroxyapatite coating serves to increase the strength of the coating, at the same time reducing the solubility of the coating. Furthermore, the thermal treatment has the positive effect that the surface of still adhering Ca (OH) ₂ particles is released when the treatment temperature is above 580 ° C. Preferably, the treatment temperature is above 600 ° C, especially at 650 ° C. Before etching, electroplating and annealing, the contact area can be microstructured. The microstructure is used in addition to the surface enlargement and the limited form fit for the ingrowing connective tissue from damage to the surface coating of the nanostructure from damage during mechanical overload or shock.

Furthermore, the nanostructured coating can be additionally functionalized, for example with an oxygen plasma, so that the wettability and thus the capillary effect can be further increased. The interconnecting nanoporous coating can be additionally coated or infiltrated with organic substances such as integrins, fibrin or RGD peptides. As an additional coating with organic substances for an antibacterial effect, for example, chitosan is suitable, which also has a healing effect in addition to an antibacterial effect, which is particularly advantageous in the skin penetration. As inorganic substances silver or copper compounds, fluoroapatite or polymers can be used, which can be applied either in the pores or as an absorbent cover layer.

The invention may further provide that the nanostructured surface is covered with resorbable coatings. These may be polymers such as polylactide or even metals such as magnesium. In this way, it is possible that the nanostructured surface is opened only after wound healing, so that the specific protein fibers such as laminin or other anchor proteins are integrated into the nanopores only after wound healing. This can lead to improved epi- lead to cell adhesion. These resorbable coatings may additionally be doped with antiseptic substances such as, for example, silver or their soluble salts, such as silver nitrates, or as organic substances, such as chitosan. Embodiments of the invention will be explained in more detail with reference to the accompanying figures. Show it:

Figure 1 - a schematic representation of an implant system; FIG. 2 shows a schematic detail of the implant system in the area of the

Skin passages s;

FIG. 3 shows a schematic detail of an implant surface; Figure 4 - a SEM image;

FIG. 5 shows an SEM image of a cut sample; such as

FIG. 6 shows a schematic representation of an implant coating with a reaction zone.

FIG. 1 shows a schematic sectional view of a percutaneous implant system 1 in an implanted position. The implant system 1 has an implant component 600 anchored in the bone tissue 50, which is anchored via form-fitting means 610, for example a thread or other form-locking elements. The osseär ancherte implant component 600 preferably has a structured surface in the contact area 61 1 between the bone tissue 50 and the implant component 600, which facilitate growth and ingrowth into the bone tissue 50. For this purpose, microstructured surfaces can be formed on the implant component 600; Likewise, the surfaces can be provided with a nanoporous, interconnecting structure of hydroxyapatite having a pore size below 1 μm in order to prevent fibrous encapsulation. The surface structure of the implant component 600 is three-dimensional and open-pored, in order to improve the to allow for growth. The bone 50 is predominantly surrounded by muscle tissue.

Attached to the distal end of the osseously anchored implant component 600 is a second implant component 700 positioned in the soft tissue 40 consisting of muscle and connective tissue. This second implant component 700 can be screwed onto the osseär anchored implant component 600, plugged or otherwise permanently, but preferably releasably secured. On the second implant component 700 positioned in the soft tissue 40 or in the muscle tissue, laterally projecting soft tissue anchors 73 are arranged, either attached thereto or formed integrally with the second implant component 700. The soft tissue anchors 73 may also be microstructured and have a nanoporous interfacial structure of hydroxyapatite; Thus, a three-dimensional, open-pore, porous surface structure in the nanoscale is provided. Over the entire region 710, in which the second implant component 700 is in contact with the muscle tissue or soft tissue 40, it forms an interface 71 1 between the second implant component 700 and the soft tissue 40. The surface of this region 710 can also be microporous and nanoporous with interconnecting pores of hydroxyapatite and have an open-pored, porous surface, preferably in a thickness below 10 μm, with a pore size below 1 μm.

The soft tissue anchors 73 serve to stabilize the soft tissue 40 in the immediate vicinity of the implant system 1 and to avoid relative movements between the soft tissue 40 and the second implant component 700. The soft tissue anchors 73 may also include microporous and nanoporous structures of hydroxyapatite with interconnecting pores and vice versa a body of the implant component 700 to be wrapped or attached.

Proximally spaced from the contact region 730 is an attachment portion 720 of the cutis which begins with the interlayer tissue proximal to the subcutis. Distally to the contact area 730 is present, which is in the skin passage in contact with the epidermis 10 and therefore may also be referred to as a skin passage area, wherein the skin with the subdermal tissue together can be regarded as a unit. The skin of dermis and epidermis together is about 1.mm thick and forms a unit with the subdermal tissue, which can be up to several millimeters thick.

At the distal end of the second implant component 700, there is an extracorporeal fitting 800 having a base 810 and attachment means for receiving, for example, prosthetic components or epithesis components.

Notwithstanding the illustrated implant system comprising a bone anchored implant component 600, an implant component 700 anchored in the soft tissue 40 and an extracorporeal endpiece 800, which is provided in particular as a load-bearing implant system for connecting prostheses to a bone stump, for example a femoral stump, at a lower load the area with the tissue anchors 73 are omitted so that the epithelial passage or skin passage takes place immediately after the bone anchoring. For medical-technical applications, for example in the case of a catheter, it is possible to dispense with the osseous anchoring, so that only soft-tissue anchors 73 are provided on the corresponding implant component 700 for soft-tissue anchoring.

The structure according to FIG. 1 with the osseously anchored implant component 600, the shaft region 700 in contact with muscles and subcutaneous tissue or connective tissue and a percutaneous region with the 3-phase line and an exclusively extracorporeal region can be changed depending on the anatomical situation. For example, the shaft area can be omitted at a transphalangeal amputation level, the osseär anchored area can be omitted in port systems. Soft tissue anchors 73 may be located in the shaft area in contact with muscles and subcutaneous tissue or connective tissue as well as in the dermal area of the cutis.

If soft tissue anchor 73 is arranged on the implant 1 in the intracorporeal region. The soft tissue anchors 73 are advantageously arranged immediately proximal to the region of permanent contact of the main tissue with the implant 1 in order to provide continuous covering of the soft tissue anchor 73 with the skin tissue sure. The skin tissue anchor 73 may also have a surface with a nanoporous hydroxyapatite interconnecting structure as in the 3-phase line region. Since the soft tissue anchors 73 are located in a subcutaneous region, the pore size can also be greater in order to also allow connective tissue to grow in or grow through it. In particular, constructive designs for the neo askularisation of the subcutaneous tissue are provided here, which have the task of intercepting effects of mechanical stress in the area of the skin penetration. For neovascularization, for example holes with a diameter between 0.5 to 5 mm are advantageous. FIG. 2 shows the region of the skin passage of a percutaneous implant 1 in an enlarged detail. The attachment region 720 lies in the region of the connective tissue 30, the contact region 730 arranged distally there can be subdivided into three subregions 731, 732 and 733, FIG. 2 particularly showing the second subregion 732 of the contact region 730, in which the skin 10 occurs after insertion of the implant system 1 in direct contact with the implant surface.

Proximally of the second subregion 732, the subdermal subregion 731 follows, which comes into contact with a so-called intermediate tissue layer of fasciae 32 or fatty tissue with fat cells 31 or directly with the connective tissue 30. Soft tissue anchors 73 may also be positioned in the subdermal subregion 731. Proximal then follows connective tissue 30 or already muscle tissue 40, where also soft tissue anchor 73 can be positioned. It seems to make sense to place the soft tissue anchor 73 as close to the skin as possible, ie to arrange it subdermally.

The attachment and contact areas 720 and 730, in which the implant component 700 in contact with the skin 10, the intermediate tissue, the connective tissue 30, usually from connective tissue cells, the so-called fibroblasts, is followed by an extracorporeal portion 733, which may be polished. Due to various external influences, be it mechanical or physiological in nature, the skin tissue can shift along the longitudinal extent of the implant component 700, ie the skin can retract or advance and thereby cover a different area of the contact area 730 and thus change the length of the extracorporeal partial area 733 , so that the extracorporeal portion 733 is also to be regarded as a contact area. The attachment and contact regions 720, 730 preferably have a nanoporous, interconnecting structure of hydroxyapatite, preferably with decreasing porosity in the distal direction.

FIG. 2 shows the maximum distal position with the reference numeral 10a; the maximum proximal position of the epithelium 10 is described by the reference numeral 10b. Between these extremes, the skin tissue can attach to the implant.

Adjoining the distal end of the second subregion 732 with a temporally long-term contact with the skin tissue is an extracorporeal subregion 733 and, if appropriate, temporary temporary contact with the skin tissue. This range corresponds to a standard polished titanium surface and may additionally contain antibacterial substances. This is followed by the extracorporeal connecting element 800 (not shown), for example in the form of an end cap.

FIG. 3 shows the interface between the surface of the second sub-area 732 and the area of the skin in the region of the 3-phase line. On the outside of the contact region 730 and thus of the second subregion 732, a microstructure 3 is applied, which obtains a certain roughness, for example by surface etching. This microstructure shows a defined high-low structure, which has a size range of 1 μιη to 5 μηι. The enlarged surface creates multiple anchor positions for adherent cells. Alternatively, by means of other coating methods, such as the plasma spray method with microparticles, an application sintering or a casting technique, a corresponding microstructure can be produced on the implant. Likewise, a particle ₁ radiate or a laser structuring a high-depth structure can be generated. A further advantage here is a distally decreasing roughness.

Onto this microstructure 3, the coating with nanoporous interconnecating structure of hydroxyapatite is applied, which may also contain other constituents. These approximately Ι μηι to 5 thick thin-film coatings obtained largely the underlying topography of the base material and can temporarily, for example, during a healing phase, be so thick that they temporarily change the topography qualitatively, since these coatings are subject to biocorrosion.

The pores 2 serve to penetrate collagenous fibers 4 and to bind fibroblasts 5 of the dermis 20, in order to achieve optimum attachment of the skin tissue to the implant. The second subregion 732 can be subdivided into a proximal region 7321 and into a transition region 7322, wherein in the proximal region 7321 a coarser structure of the pores compared to the pores in the transition region 7322 is present. The pores become smaller distally and are ideally absent above the 3-phase line.

FIG. 4 shows a scanning electron micrograph of the surface coating of an implant which was produced by the method according to the invention and which shows a nanoporous and interconnecting structure of hydroxyapatite on the implant component 700 or on the soft tissue anchor 73.

FIG. 5 shows an enlarged illustration of the interconnecting nanoporous hydroxyapatite layer in cross-section. The hydroxyapatite layer with the pores 2 is shown on a titanium substrate as part of the implant component 700. The illustration is a scanning electron photomicrograph in cross-section, which was produced with a FIB (Focued Ion Beam).

FIG. 6 shows a schematic representation of the connection of a skin cell to the implant coating. The implant with the implant component 700 has on the outside a coating of hydroxyapatite with a nanoporous Structure, wherein the pores are formed interconnecting. The tissue symbolized by the cell 33 anchors to the collagen fibers and anchor proteins in the nanoporous structure of the hydroxyapatite, which in turn is connected to the titanium implant 700. The nanoporous and interconnecting hydroxy-lapatite coating is thus the interface between the implant and the tissue and represents a hybrid region in which both cell biology and synthetic material are present. Advantageously, this hybrid region allows an exchange of ions and signal substances by the capillary effect of the nanoporous and interconnecting structure in the direction of the cells 33, so that the cells can also be supplied with nutrients from the implant side. Substances which promote cell adhesion or may have an antibacterial effect may be present in the hydroxyapatite. The reaction region, also called hybrid region, between the implant 700 and the tissue 33 is shown in the upper area of FIG. 6 in the form of the arrows overlapping one another.

Based on an embodiment, the method for producing a coating according to the invention and an implant according to the invention will be explained below. A percutaneous implant with a grade 4 pure titanium soft tissue anchor is to be coated for craniofacial application with a nanoporous and interconnecting hydroxyapatite coating in the area of the skin contact and the intracorporeal area. At the beginning of the coating process according to the invention, the intracorporeal areas, which are thus in contact with the soft tissue, are microstructured by pickling. The non-microstructured areas, ie the polished surfaces, which are present extracorporeally, as well as the area of the skin contact are masked for this purpose with shrink tubing. By pickling the titanium surface is chemically removed in such a way, especially in non-uniform oxide layers, that thereby high-low structures of about 2 to 5 μηι arise. The pickling solution consists of a mixture of 88% water, 2% hydrofluoric acid (40%) and 10% nitric acid (65%). The pickling time is 2 minutes. Due to extended pickling times and other additives Sets in the standard acid, the microstructure on the titanium surface can be varied.

In the intracorporeal area and in the contact area, where the skin is supposed to grow, the microstructured surfaces are further nanostructured. For this purpose, the surfaces are etched in a 5 M NaOH solution, with the remaining surfaces being masked again with shrink tubing. The basic etching is carried out at room temperature for at least 20 hours. The resulting surface structure now consists of a sodium titanate hydrogel layer and has a thickness of about 1 to 2 μη. The still soft structure is characterized by the fact that they form very fine, three-dimensional, net-like structures in the nanoscale. By the subsequent rinsing in deionized water, the sodium is rinsed as far as possible. In the subsequent manufacturing process, the bar-like three-dimensional nanostructures are coated with nanocrystalline calcium phosphate by means of a wet-chemical coating process. The implant to be coated is connected as a cathode, the anode is a platinum electrode. The applied voltage and the exposure time are of great importance for the coating or infiltration into the nanoporous, interconnecting structure. The exact voltage must be determined empirically and is 10% below the electrolysis voltage present in the system. Too low stresses do not lead to timely deposition, and too high stresses on the one hand damage the surface by hydrogen evolution, on the other hand, the structure is not evenly coated in the nanopores. In the standard electrolyte solution, consisting of a 0.025 M Ca (OH) ₂ solution and a 0.05 MH ₃ P0 ₄ solution and a pH of 4.0, the coating voltage of 2.7 V to 3.3 V in a Time of 2 minutes continuously increased. Additives, such. As magnesium or strontium in the form of hydroxides, can be added to the electrolyte. The electrochemical deposition of calcium phosphates with or without additives is based on their pH-dependent solubility, so that the adjustment of the ph value is to be adapted to the respective system with the corresponding additives. The uncoated areas, ie the extracorporeal areas, are still masked with the shrink tubing during the coating process. In the further process step, the calcium phosphate from the electrochemical coating is hydrothermally converted into hydroxyapatite. This process is carried out in an alkaline solution, preferably in an ImM Ca (OH) ₂ solution at temperatures of 150 ° C and pressures of 4 bar. The masking tubes are removed first.

The final tempering process stabilizes and solidifies the hydroxyapatite in the nanoporous and interconnecting surface. The thermal treatment is carried out at 600 ° C and at least 2 hours. The heating and cooling rate is 5 ° C / min. In this case an inert furnace atmosphere, preferably with argon, 5.0 should be used.

Claims

claims

A percutaneous implant (1) having an extracorporeal area and an intracorporeal area (600, 700) and a contact area (730) in which skin tissue (10) comes into contact with the implant (1), characterized in that the contact area (730), the surface has a porous structure with interconnecting pores (2) and the pore size is less than 1 μηι.

2. Implant according to claim 1, characterized in that the contact region (730) comprises a calcium phosphate coating and / or an apatite coating, in particular a fluorohydroxil or hydroxyapatite coating.

3. Implant according to claim 1 or 2, characterized in that the contact region (730) celladhäsionsfördernde additives of alkali metals and alkaline earth metals, in particular magnesium, strontium, sodium and potassium or a mixture of at least two of these elements.

4. Implant according to one of the preceding claims, characterized in that the contact region (730) contains antibacterial additives, in particular silver, copper, magnesium or zinc or salts thereof or a mixture of at least two of these elements or their salts.

5. Implant according to one of the preceding claims, characterized in that the pore size and / or pore density decreases in the distal direction.

6. Implant according to one of the preceding claims, characterized in that the entire intracorporeal region (600, 700) has a surface such as the contact region (730).

7. Implant according to one of the preceding claims, characterized in that on the implant (1) in the intracorporeal region (600, 700) at least one soft tissue anchor (73) is arranged.

8. Implant according to claim 7, characterized in that the soft tissue anchor (73) has a surface with a porous structure such as the contact area (730).

9. Implant according to one of the preceding claims, characterized in that the intracorporeal region (600, 700) has at least one device (610) for anchoring in a bone (50).

10. Implant according to claim 9, characterized in that the anchoring device (610) has positive locking elements.

11. Implant according to claim 9 or 10, characterized in that the surface of the anchoring device (610) has a surface with a porous structure such as the contact region (730).

12. Implant according to one of the preceding claims, characterized in that at the distal end of the extracorporeal area (800) receiving means (810) are formed for connection elements.

13. Implant according to one of the preceding claims, characterized in that the implant (1) is made of titanium or a titanium material as a carrier of a surface coating.

14. Implant according to one of the preceding claims, characterized in that in the intracorporeal region (600, 700), a microstructure (3) is formed, which is between 2 μηι μπι and 100 deep.

15. Implant according to claim 14, characterized in that the depth of the microstructure (3) decreases in the distal direction.

16. Implant according to one of the preceding claims, characterized in that the contact region (730) and the intracorporeal region (600, 700) are connected to a ner absorbable cover layer of ceramic, polymeric, biopolymeric or metallic materials is coated.

17. Implant according to one of the preceding claims, characterized in that the contact region (730) and the intracorporeal region (600, 700) is physically or chemically functionalized and / or coated with growth factors or proteins.

18. Implant according to one of the preceding claims, characterized in that the porous structure is provided with wound-healing or antibacterial agents.

19. A method for producing an implant according to one of the preceding claims, characterized in that etched at least in the contact region (730) a support of titanium or their alloys and the support surface is coated with calcium phosphate and hydrothermally converted into an apatite and then thermally treated.

20. The method according to claim 19, characterized in that a basic etching, in particular a NaOH etching is carried out.

21. The method according to claim 19 or 20, characterized in that the etched surface electrochemically coated with the calcium phosphate layer, which is then hydrothermally converted in an alkali into an apatite layer with nanoporous, interconnecting pores.

22. The method according to any one of claims 19 to 21, characterized in that the contact region (730) and / or the intracorporeal region (600, 700) is microstructured prior to etching and coating.

23. The method according to any one of claims 19 to 22, characterized in that the thermal treatment at temperatures above 600 ° C, in particular at 650 ° C is performed.