Wound dressing comprising a wound contact layer with a track-shaped coating for directed cell migration

Description

[0001] The present invention relates to a wound dressing comprising a wound contact layer, wherein a wound-facing side of the wound contact layer has a coating. The invention also relates to a method for producing the aforementioned wound dressing.

[0002] Wound dressings with a coated wound contact layer are known in the art. The coating can impart a specific property to the wound contact layer, for example, antibacterial effectiveness in the case of a silver coating or a non-adherent surface in the case of an ointment or silicone coating. In the aforementioned examples, the coating is often applied to the entire surface of the wound contact layer, to a surface with openings, or in spots.

[0003] Wound dressings with a hydrogel wound contact layer are also known in the art. Such dressings can both absorb wound exudate and moisturize the wound. Wound dressings with a hydrogel wound contact layer have achieved high status in modern wound treatment. The further development of this proven technology is a concern of both users and industry.

[0004] US 2011 / 0189287 A1 discloses a wound dressing comprising a carrier material with a wound-facing surface, wherein the wound-facing surface is modified with a special matrix material. Upon application to a wound, the surface of the carrier material modified with the matrix material is brought into contact with the wound bed. The matrix material can contain an active ingredient. It is intended to modify the wound bed, thus creating a homogeneous environment that enables the uniform and predictable release or absorption of active ingredients into the wound bed.

[0005] The object of the present invention was to provide a wound dressing that can specifically influence the cells in a wound.

[0006] In particular, the object of the present invention was to provide a wound dressing with which the cells in a wound can be specifically influenced in order to positively influence the wound healing process, for example by accelerating wound closure.

[0007] A further object of the present invention was to provide a manufacturing process for such a wound dressing that is as simple and economical as possible.

[0008] To achieve these objects, a wound dressing according to claim 1 and a method according to claim 2 are proposed.

[0009] The wound dressing according to the invention comprises a wound contact layer, wherein the wound contact layer comprises or consists of a hydrogel, and a wound-facing side of the wound contact layer has a coating. The coating can promote cell adhesion of a patient. This means that the patient's cells can adhere to the coating. Furthermore, the coating forms one or more tracks on the wound-facing side of the wound contact layer. Because the coating can promote cell adhesion and is designed in a track-like manner, the wound dressing can specifically influence the cells in a wound.

[0010] Whether a material can mediate cell adhesion within the meaning of the present invention can be determined, for example, with the help of a cell culture experiment. If adherently growing cells, such as L929 fibroblasts, adhere to the material in the cell culture and cannot be washed off (and thus can serve as a substrate for the cells), the material can mediate cell adhesion within the meaning of the present invention.

[0011] The method according to the invention for producing a wound dressing comprises the following steps: i. Providing a wound contact layer, wherein the wound contact layer comprises or consists of a hydrogel. ii. Coating a wound-facing side of the wound contact layer such that the wound-facing side of the wound contact layer has a coating, wherein the coating can mediate adhesion of cells of a patient and the coating forms one or more tracks on the wound-facing side of the wound contact layer.

[0012] The term "cells" refers to human or animal cells. Microorganisms, such as bacteria in particular, are not included. When treating a wound in a human or animal with the wound dressing according to the invention, the cells intended to adhere to the coating typically originate from the treated human or animal (the "patient") itself.

[0013] The wound dressing according to the invention is intended for the treatment of external or open skin wounds. The wound is covered with the wound dressing. The side of the wound contact layer facing the wound comes into contact with the surface of the wound. Cells involved in wound healing, such as fibroblasts or keratinocytes, can then adhere to the coating and move along the coating's paths. In this way, the cells can be guided, for example, from an edge of the wound into the interior of the wound, and wound closure can be accelerated. Put simply, the path-like coating of the wound contact layer can be understood as a type of road system along which cells involved in wound healing are intended to move and with which they are intended to be guided, for example, from an edge of the wound into the interior of the wound, thereby accelerating wound closure.The wound dressing according to the invention therefore attempts to guide cell movement, also known as migration, in a direction beneficial to the wound healing process. In simple terms, this explains how the wound dressing can specifically influence the cells in a wound to positively influence the wound healing process. Further details of the present invention can be found in the following preferred embodiments.

[0014] Preferably, the uncoated wound contact layer is essentially incapable of promoting cell adhesion. This allows the desired effect of the coating—directed cell migration—to be more effectively achieved. Furthermore, the wound contact layer can then adhere less strongly to the wound surface, which can allow for a more gentle dressing change.

[0015] According to the invention, the wound contact layer comprises a hydrogel or the wound contact layer consists of a hydrogel. A hydrogel wound contact layer can both absorb wound exudate and moisturize the wound. A hydrogel wound contact layer is suitable for the gentle treatment of many different wound types. Furthermore, a hydrogel wound contact layer can have the property of essentially not promoting cell adhesion.

[0016] A hydrogel particularly suitable for the present invention is disclosed in German patent application DE 10 2016 125 534 A1. This hydrogel is obtainable by reacting an amine-terminated prepolymer containing polyalkylene oxide units with an isocyanate-terminated prepolymer containing polyalkylene oxide units. The reaction preferably takes place in the presence of a polyhydric alcohol such as, for example, ethylene glycol, glycerol, sorbitol, PEG300, PEG2000, or sucrose. Furthermore, the reaction typically takes place in the presence of water. Furthermore, the isocyanate-terminated prepolymer can be branched in at least three branches, and the polyalkylene oxide units of the two prepolymers can be formed by polyethylene oxide and / or polypropylene oxide units, wherein the weight ratio of ethylene oxide to propylene oxide units is preferably 3:1 to 7:1.A suitable amine-terminated prepolymer is commercially available under the name Jeffamin® ED-2003 (Huntsman; Everberg, Belgium). A suitable isocyanate-terminated prepolymer is commercially available under the name Aquapol® PI-13000-31 (Carpenter; Richmond, USA). Additional information on the chemical structure of Aquapol® is contained in the European patent application with application number EP 18179037.9.

[0017] It is also advantageous in the context of the present invention if the wound contact layer is continuous and / or substantially planar. A continuous wound contact layer has a continuous surface without holes, slits, or similar openings. Such a wound contact layer can be easily structured in a variety of ways with a sheet-like coating. A hydrogel wound contact layer can easily be manufactured to be continuous and planar.

[0018] According to the invention, the coating is designed to promote cell adhesion and form one or more tracks on the wound-facing side of the wound contact layer. Typically, as already mentioned, this results in the coating being able to guide and / or promote cell migration and / or proliferation. The cells intended to adhere to the coating can advantageously be human or animal cells involved in wound healing, in particular fibroblasts or keratinocytes.

[0019] Cell adhesion to the coating can be mediated by the coating comprising an alkyl radical, an alcohol, an amine, a fatty acid, a component of an extracellular matrix (ECM component), a denatured component of an extracellular matrix, a coagulation factor, a cell adhesion molecule, a synthetic polymer, and / or a sugar. Of this group, the ECM component (undenatured), the coagulation factor, and the cell adhesion molecule are preferred, as these can mediate particularly specific cell adhesion.

[0020] The alkyl radical preferably has at least 8 carbon atoms, in particular more than 12 carbon atoms, and is also advantageously unbranched.

[0021] The alcohol and the amine likewise preferably have at least 8 carbon atoms, in particular more than 12 carbon atoms. Furthermore, the alcohol and the amine are preferably aliphatic and / or unbranched. For example, the alcohol can be tridecan-1-ol, tetradecan-1-ol, pentadecan-1-ol, hexadecan-1-ol, or octadecan-1-ol. However, the alcohol can also be a monoglyceride or a diglyceride, in particular as an ester of glycerol with one or two fatty acids according to the following preferred embodiments.

[0022] The fatty acid is preferably medium-chain or long-chain. A medium-chain fatty acid has 8 to 12 carbon atoms. A long-chain or higher fatty acid has more than 12 carbon atoms. Both saturated and unsaturated fatty acids are considered, which are preferably unbranched. Accordingly, the fatty acid can be, for example, tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid, octadecanoic acid, oleic acid, linoleic acid, or linolenic acid.

[0023] The component of an extracellular matrix can be, for example, elastin, entactin, fibronectin, hyaluronic acid, collagen, laminin, or vitronectin. The two adhesion proteins fibronectin and vitronectin are particularly preferred. The term collagen refers not only to type I collagen, but also to any other collagen type. Likewise, the term laminin refers not only to laminin-1, but also to any other form of laminin. The denatured component of an extracellular matrix can be, for example, gelatin.

[0024] The coagulation factor is preferably fibrinogen. It has been shown that fibrinogen can also advantageously mediate cell adhesion to the coating if this coagulation factor is included in the coating.

[0025] Cell adhesion molecules are membrane proteins that can contact neighboring cells or the extracellular matrix. The cell adhesion molecule can be a cadherin, an integrin, or a selectin. Cadherins and selectins can bring cells into contact with each other, whereas integrins and selectins can initiate cell-matrix contacts. In the context of the present invention, those cell adhesion molecules that are designed to contact neighboring cells are particularly advantageous. Accordingly, cadherins and selectins are preferred cell adhesion molecules for the present invention.

[0026] Polylysine, in particular, can be included in the coating as a synthetic polymer. Finally, the sugar is preferably oligomeric (oligosaccharide) or polymeric (polysaccharide). In particular, the sugar is a polysaccharide.

[0027] The coating may also contain derivatives or fragments, particularly the respective cell-binding domains, of the aforementioned substances that mediate cell adhesion. It is also possible for the coating to contain several of the aforementioned substances that mediate cell adhesion. For example, the coating could contain both fibronectin and fibrinogen. Furthermore, most of the aforementioned substances that mediate cell adhesion can be of natural origin or artificially produced, for example, through a biotechnological manufacturing process.

[0028] As already described, the coating according to the invention forms one or more tracks on the wound-facing side of the wound contact layer in order to guide cell migration in a direction beneficial for wound healing. Preferably, the one or more tracks run from an edge region of the wound-facing side of the wound contact layer to at least a central or central region of the wound-facing side of the wound contact layer. This configuration is considered advantageous for the wound healing process because cells can then be guided from the wound edge into the wound.

[0029] In particular, the one or more webs may form a grid-shaped, star-shaped or radial pattern on the wound-facing side of the wound contact layer.

[0030] The grid-like pattern can comprise essentially parallel and essentially rectilinear paths. The radial pattern, in contrast, can comprise essentially rectilinear paths, wherein the paths are arranged around a substantially central region of the wound-facing side of the wound contact layer, pointing in different directions. Preferably, the pattern extends over essentially the entire surface of the wound-facing side of the wound contact layer. This means that predominantly the entire surface of the wound-facing side of the wound contact layer, and not just a portion thereof, is patterned. A coating with such a pattern can be well suited for directed cell migration into the wound.

[0031] As with the shape or course of the tracks, different variations are also possible with regard to the width of the tracks. Thus, the one or more tracks can each have a width of 10 µm to 500 µm, preferably 10 µm to 400 µm, more preferably 10 µm to 300 µm, even more preferably 10 µm to 200 µm, and particularly preferably 10 µm to 100 µm. A coating with wider tracks may be easier to implement technically than a coating with narrower tracks. In contrast, a coating with narrower tracks may guide cell migration better than a coating with wider tracks.

[0032] The spacing between the tracks can be 200 µm to 5000 µm, preferably 200 µm to 1000 µm, more preferably 200 µm to 500 µm, even more preferably 200 µm to 400 µm, and particularly preferably 200 µm to 300 µm. The more densely the tracks are arranged, the more cells can be guided. However, the spacing should be at least large enough so that the cells cannot span the tracks. This should be achieved at the previously specified lower limit of 200 µm, especially for fibroblasts and keratinocytes.

[0033] Furthermore, the coating is preferably present on a maximum of 10%, 20%, 30%, 40%, or 50% of the surface of the wound-facing side of the wound contact layer. A full-surface coating of the wound-facing side of the wound contact layer is not provided for by the invention, since this normally does not allow for the formation of webs.

[0034] Various technologies can be used to apply the coating to the wound contact layer. For example, the coating can be produced using microcontact printing. According to a particularly preferred embodiment of the invention, however, it is proposed that the coating be produced using inkjet printing. With inkjet printing, web-like coatings for wound dressings in a wide variety of shapes and sizes can be produced comparatively easily, quickly, and cost-effectively. Inkjet printing can also be carried out under sterile conditions. Due to the advantages mentioned above, inkjet printing is better suited to industrial wound dressing manufacturing processes than microcontact printing. Inkjet printing and the devices used for this purpose, the inkjet printers, are known in the prior art.In the context of the present invention, the "ink" refers to the coating in the liquid state.

[0035] Inkjet printing can be CIJ printing. CIJ printing stands for "continuous ink jet" printing. In CIJ printing, the inkjet printer continuously generates droplets and applies them to a surface (in this case, the wound contact layer). With regard to the present invention, CIJ printing has the advantage that the wound contact layer can be coated very quickly. However, due to process-related reasons, some of the generated droplets may remain unused in CIJ printing, which can increase the amount of coating solution required and thus the costs.

[0036] As an alternative to CIJ printing, DOD printing is provided. DOD printing stands for "drop on demand" printing. With DOD printing, the droplets are generated only when needed. This allows the wound contact layer to be coated very efficiently and economically, which is considered particularly advantageous for the present invention. Preferably, DOD printing is carried out with multiple spray nozzles. This means that the inkjet printer used has multiple spray nozzles and can then coat the wound contact layer at a similar speed to a CIJ printer. For example, in this preferred embodiment of the invention, the DOD printer can have two or three spray nozzles instead of just a single one.

[0037] Further advantageous embodiments of the invention can be specified with regard to the attachment of the coating to the wound contact layer, wherein it is particularly assumed that the wound contact layer is a hydrogel. The material used for the coating (preferably a solution applied to the wound contact layer by inkjet printing) is intended to form a layer or ply on the wound contact layer. Normally, this is a prerequisite for the cells to be able to come into contact with the substances contained in the coating that promote cell adhesion. Accordingly, it is typically not intended in the present case for the material used for the coating to completely penetrate the wound contact layer.However, it may be advantageous if the coating at least partially penetrates the wound contact layer in order to achieve permanent attachment of the coating to the wound contact layer. It may also be advantageous if the coating does not substantially penetrate the wound contact layer, but is essentially merely deposited on top of the wound contact layer in order to fully exploit the cell adhesion-promoting effect of the coating. In the two aforementioned embodiments, particular reference is made to the cell adhesion-promoting substances contained in the coating. Auxiliaries used for coating the wound contact layer without a cell adhesion-promoting effect (e.g., solvents) can be disregarded in the two aforementioned embodiments.For example, in the case of a hydrogel wound contact layer coated with an aqueous fibrinogen solution using inkjet printing, particular reference is made to the penetration depth of the fibrinogen molecules, not the water molecules. Whether the coating penetrates the wound contact layer or not can be determined in case of doubt using suitable microscopic or spectroscopic methods. Suitable microscopic methods could include confocal microscopy or fluorescence microscopy using appropriate fluorescent dyes. Confocal RAMAN spectroscopy could be used as a suitable spectroscopic method.

[0038] A particularly permanent attachment of the coating to the wound contact layer can be achieved by chemically covalently bonding the coating to the wound contact layer. Here, particular reference is again made to the substances contained in the coating that promote cell adhesion. However, it can also be advantageous if the coating, or the substances contained in the coating that promote cell adhesion, are not chemically covalently bonded to the wound contact layer, but simply adhere to the wound contact layer, for example, based on hydrophilic, hydrophobic, or ionic interactions. In this case, there is no change in the coating on a chemical level, and the cell adhesion-promoting effect of the coating can be fully retained. Furthermore, such adhesion can be more easily realized technically and is also surprisingly stable.If the coating adheres only to the wound contact layer as described above, there is typically no specific interaction, such as between biotin and avidin, biotin and streptavidin, and / or an antigen and an antibody, to attach the coating to the wound contact layer. Therefore, adhesion typically does not involve an interaction between biotin and avidin, biotin and streptavidin, and / or an antigen and an antibody. Rather, an easily achievable nonspecific adhesion is intended.

[0039] The extent to which a coating material can penetrate into and / or react with a hydrogel wound contact layer depends, for example, on the following factors: First, the polymerization state of the hydrogel, i.e., whether the hydrogel is already fully cross-linked or still reactive. The latter generally favors the penetration of the coating material into the hydrogel and the reaction of the coating material with the hydrogel. Second, the molecular structure of the (fully polymerized) hydrogel. The more open-meshed the hydrogel network, the better the coating material should be able to diffuse and penetrate into the hydrogel. Third, the molecular weight of the coating material. The lower the molecular weight, the better it should be able to diffuse and penetrate into the hydrogel. Fourth, the match between the chemical properties of the hydrogel and the coating material. For example, a hydrophilic coating material will usually be able to penetrate a hydrogel better than a hydrophobic coating material.Different charges of the hydrogel and coating material can also contribute to the coating material penetrating the hydrogel better.

[0040] Of the four factors mentioned above, the first factor is particularly relevant. Therefore, a further embodiment of the invention relates to the wound contact layer comprising or consisting of a hydrogel, and the coating being applied to the wound contact layer, in particular to the hydrogel, at a time when the hydrogel is not yet fully cross-linked but is still reactive, so that the coating can penetrate into the wound contact layer, in particular into the hydrogel, and / or react with the wound contact layer, in particular with the hydrogel, and form a chemically covalent bond. The covalent bond between the coating and the hydrogel can be formed, for example, by components of the coating having an amine or hydroxyl group reacting with the aforementioned isocyanate-terminated prepolymer.Many of the previously mentioned cell adhesion-promoting substances contain an amine or hydroxyl group and are therefore able to react with the isocyanate-terminated prepolymer, forming a urea bond (when the amine group reacts with the isocyanate group) or a urethane bond (when the hydroxyl group reacts with the isocyanate group).

[0041] Alternatively, it can be provided that the wound contact layer comprises a hydrogel or consists of a hydrogel and the coating is applied to the wound contact layer, in particular to the hydrogel, at a time when the hydrogel is completely cross-linked and no longer reactive, so that the coating cannot penetrate into the wound contact layer, in particular into the hydrogel, and / or cannot react with the wound contact layer, in particular with the hydrogel, and cannot bond chemically covalently.

[0042] The embodiments described above with regard to the attachment of the coating to the wound contact layer can also be advantageously combined with one another. For example, the coating can penetrate into the wound contact layer and simultaneously be chemically covalently bonded to it. The coating is then particularly strongly bonded to the wound contact layer. However, the coating can also simply be applied to the wound contact layer in an adhesive manner in order to optimally utilize its cell adhesion-promoting effect. Other variants, such as a coating that penetrates into the wound contact layer but is not chemically covalently bonded to the wound contact layer, are also conceivable.

[0043] The wound dressing according to the invention comprises at least one layer, namely the wound contact layer with the coating. Advantageously, however, the wound dressing is also provided with additional layers. For example, the wound dressing may further comprise a backing layer, in particular a backing layer made of a polyurethane film. The backing layer may be bonded to a side of the wound contact layer facing away from the wound. The backing layer essentially serves to protect the wound contact layer or all layers of the wound dressing arranged beneath it from contamination and mechanical stress.

[0044] The backing layer can also serve to secure the wound dressing to the patient's body. For this purpose, the backing layer can overlap the wound contact layer and form an adhesive edge. The wound dressing is then designed in the form of an island dressing.

[0045] Furthermore, the wound dressing may further comprise an absorbent layer, in particular an absorbent layer made of polyurethane foam. This provides the wound dressing with greater absorption capacity. The absorbent layer may be bonded to the side of the wound contact layer facing away from the wound. The aforementioned backing layer may then be bonded to a side of the absorbent layer facing away from the wound, resulting in an arrangement in which the absorbent layer is located between the wound contact layer and the backing layer.

[0046] In the case of an additional backing layer, the method according to the invention may comprise the further steps iii. and iv. mentioned below: Method for producing a wound dressing, comprising the following steps: i. Providing a wound contact layer. ii. Coating a wound-facing side of the wound contact layer such that the wound-facing side of the wound contact layer has a coating, wherein the coating can promote cell adhesion and the coating forms one or more tracks on the wound-facing side of the wound contact layer. iii. Providing a backing layer, in particular a backing layer made of a polyurethane film. iv. Bonding a side of the wound contact layer facing away from the wound to the backing layer, wherein the backing layer preferably overlaps the wound contact layer and forms an adhesive edge.

[0047] In the case of an additional backing layer in combination with an additional absorbent layer, the method according to the invention may comprise the further steps iii. to vi. mentioned below: Method for producing a wound dressing, comprising the following steps: i. Providing a wound contact layer. ii. Coating a wound-facing side of the wound contact layer such that the wound-facing side of the wound contact layer has a coating, wherein the coating can mediate adhesion of cells and the coating forms one or more webs on the wound-facing side of the wound contact layer. iii. Providing a backing layer, in particular a backing layer made of a polyurethane film. iv. Providing an absorbent layer, in particular an absorbent layer made of a polyurethane foam. v. Connecting a side of the wound contact layer facing away from the wound to the absorbent layer. vi. Connecting a side of the absorbent layer facing away from the wound to the backing layer, wherein the backing layer preferably overlaps both the absorbent layer and the wound contact layer and forms an adhesive edge.

[0048] The present invention further relates to a wound dressing obtainable by the method according to the invention. Furthermore, the present invention further relates to a specific medical indication for the wound dressing according to the invention. The wound dressing according to the invention is used to treat a wound that is in a granulation phase or an epithelialization phase. The wound dressing according to the invention can be particularly well-suited for these two phases of the wound healing process. Examples and figures

[0049] The following examples and figures are intended to explain and illustrate the invention in more detail. Identical structural elements may be identified by the same reference numerals in the figures. Figure 1 shows a first embodiment of a wound dressing according to the invention 1from the side or in a cross-sectional view. The wound dressing 1 includes a backing layer 2. At the back layer 2 It can be a waterproof, water vapor permeable polyurethane film. Furthermore, the wound dressing includes 1 a wound contact layer 3, which preferably consists of a hydrogel. The wound contact layer 3 According to the invention, it has a web-shaped coating to which cells can adhere (not shown in Figure 1 ).Cell adhesion is mediated by suitable substances contained in the coating, such as fibronectin, vitronectin, or fibrinogen. Ideally, the coating should then promote directed migration of the adhered cells, for example, into the wound, thereby accelerating the wound healing process. Suitable designs of the sheet-like coating are shown in the following figures. Figure 2 shows the underside of the wound dressing 1. As in Figure 2 shown the coating 4 on a wound-facing side of the wound contact layer 3 (Underside of the wound dressing 1) a grid-like pattern with several parallel and straight lines. The lines connect two opposite edge areas of the wound contact layer 3 and run over a central area and partly also a central area of ​​the wound contact layer 3.The position of the central area is in Figure 2 with the dashed line 5 The position of the central area is indicated in Figure 2 with the dashed circle 6 The width of the webs, preferably produced by DOD printing, can range from 10 µm to 500 µm, for example, and is not shown to scale in the drawings. The dimensions of the wound dressing 1 can, for example, be in a range from 5 cm x 5 cm to 20 cm x 20 cm. Figure 3 shows a second embodiment of a wound dressing according to the invention 7 View of the underside similar to the previous figure. Compared to the wound dressing 1 the coating can 8 in the wound dressing 7 be regarded as a single path, which is meandering over the wound contact layer 3 Nevertheless, the coating is 8in terms of their patterning essentially with the coating 4 out of Figure 2 and is also referred to as lattice-shaped in this case. Figure 4 shows a third embodiment of a wound dressing according to the invention 9 as before, looking at the underside. The wound dressing 9 differs from the wound dressing 1 or 7 only because the coating 10 has a different pattern. The coating 10 forms a radial pattern with several straight lines, with the lines circling around a central area 6 the wound contact layer 3 are arranged pointing in different directions. The radial pattern could also be formed in a slightly modified form by a single track, for example if the coating tracks 10 be connected accordingly. Figure 5shows a fourth embodiment of a wound dressing according to the invention 11 from the side. Unlike the wound dressing 1, 7 or 9 includes the wound dressing 11 additionally an absorbent layer 12 between the backing layer 2 and the wound contact layer 3. The absorbent layer 12 can be made of polyurethane foam, for example. Otherwise, the wound dressing 11 like the wound dressing 1, 7 or 9 Another variation of the wound dressing 1 as a fifth embodiment of a wound dressing according to the invention 13 is in the Figures 6 and 7 The only difference in the wound dressing 13 compared to the wound dressing 1 is that the backing layer 2 the wound contact layer 3 overlapped and an adhesive edge 14This creates a so-called island structure. At least in the area of ​​the adhesive edge 14 The adhesive layer usually used, for example an acrylate adhesive, is in the Figures 6 and 7 not shown. With the adhesive edge 14 The wound dressing can be securely attached to the patient's body if the adhesive strength of the wound contact layer 3 This is usually done by ensuring that the adhesive edge 14 attached to intact skin in the wound area. The adhesive edge 14 is not intended to come into contact with the wound. Only the wound contact layer is intended for this purpose. 3 The wound dressing 13can also be provided with an additional absorbent layer and a radially patterned coating instead of a grid-like coating, as described above. The absorbent layer is then preferably exactly the same size as the wound contact layer. 3 designed so that the absorbent layer and the wound contact layer 3 can be placed flush with each other and the adhesive edge 14 is not affected. Stability of a coating produced by DOD printing

[0050] A hydrogel layer was applied to glass slides using spin coating. The hydrogel was obtained by reacting a six-arm isocyanate-terminated prepolymer containing polyethylene oxide units (provided by the DWI of the RWTH Aachen University) with water. After the hydrogel had fully polymerized on the glass slides, fibrinogen tracks were printed onto the hydrogel layers. The printing conditions are given below: Coating solution: 10 wt% fibrinogen (F8630, Sigma-Aldrich) in PBS DOD printer: 3D Discovery, regenHU Pressure: 0.2 bar Feed rate: 40 mm / min Droplet spacing: 0.2 mm Valve opening time: 100 µs

[0051] An important parameter in DOD printing is droplet size. In general, droplet size can be controlled primarily by the applied pressure, the valve opening time, and the viscosity of the coating solution. For example, droplet size generally increases when the pressure or valve opening time is increased. Conversely, droplet size typically decreases when the viscosity of the coating solution is increased. However, viscosity can only be increased within a certain range, otherwise droplets can no longer be generated. For a given droplet size, the droplet spacing must then be selected so that lanes are printed rather than just individual dots. In any case, the above-mentioned printing conditions were selected so that fibrinogen lanes of suitable width and quality could be generated on the hydrogel.

[0052] The hydrogel glass plates with the printed sheet-like fibrinogen coating are in Figure 8 The glass slides were placed on the lid of a six-well plate for printing and are marked with the dashed circles 15, 16 The coating paths are highlighted as bright lines 17 recognizable.

[0053] The printed hydrogel glass slides were then transferred to Petri dishes, moistened with demineralized water and incubated for up to nine days at 37 °C. Figure 9 shows a hydrogel glass plate with the printed sheet-like fibrinogen coating 17 after nine days of incubation in water. The fibrinogen coating did not detach from the hydrogel despite several days of incubation. This was surprising, since it is assumed here that the fibrinogen coating was essentially merely adherent to the hydrogel. Cell adhesion to a coating produced by DOD printing

[0054] Glass slides were coated with a hydrogel layer and a fibrinogen coating as previously described. The printed hydrogel glass slides were then transferred into 6-well plates and seeded with adherently growing cells (L929 fibroblasts). After a medium change and washing step, cell adhesion was examined microscopically (see Figure 10 and Figure 11 with a 4x or 10x magnification). It was shown that the cells bind to the fibrinogen pathways 17 can adhere well, while the cells essentially do not adhere to the hydrogel 18 can adhere. Creating a sheet-like fibrinogen coating using DOD printing on a hydrogel wound dressing

[0055] A wound dressing with a hydrogel wound contact layer was coated with a fibrinogen coating using DOD printing. The hydrogel was obtained by reacting an amine-terminated prepolymer (Jeffamin® ED-2003) with a three-arm branched isocyanate-terminated prepolymer (Aquapol® PI-13000-31) in the presence of water and glycerol. As in the previously described experiments, the hydrogel was printed at a time point when it was fully polymerized and no longer reactive. The printing conditions are given below: Coating solution: 10 wt% fibrinogen (F8630, Sigma-Aldrich) in PBS DOD printer: 3D Discovery, regenHU Pressure: 0.2 bar Feed rate: 40 mm / min Droplet spacing: 0.1 mm Valve opening time: 100 µs

[0056] Figure 12 shows a magnified image of the hydrogel wound contact layer with the fibrinogen coating. The layers are approximately 275 µm wide.

[0057] In summary, the experiments have shown that DOD printing can be used to create a stable sheet-like coating on hydrogels. Cells can adhere to the coating, which makes it possible to guide cell migration in a specific direction and thus trigger directional cell migration.

Claims

1. Wound dressing (1, 7, 9, 11, 13) comprising a wound contact layer (3), wherein a wound-facing side of the wound contact layer (3) has a coating (4, 8, 10), characterized in that the coating (4, 8, 10) is able to mediate adhesion of cells and the coating (4, 8, 10) forms one or more lanes on the wound-facing side of the wound contact layer (3), wherein the wound contact layer (3) comprises a hydrogel or consists of a hydrogel.

2. Method for producing a wound dressing (1, 7, 9, 11, 13), comprising the following steps: i. providing a wound contact layer (3), wherein the wound contact layer (3) comprises a hydrogel or consists of a hydrogel, ii. coating a wound-facing side of the wound contact layer (3), so that the wound-facing side of the wound contact layer (3) has a coating (4, 8, 10), wherein the coating (4, 8, 10) is able to mediate adhesion of cells and the coating (4, 8, 10) forms one or more lanes on the wound-facing side of the wound contact layer (3).

3. Wound dressing or method according to any of the preceding claims, wherein the hydrogel is obtainable by reaction of an amine-terminated prepolymer containing polyalkylene oxide units with an isocyanate-terminated prepolymer containing polyalkylene oxide units, wherein the reaction takes place preferably in the presence of a polyhydric alcohol, more particularly ethylene glycol, glycerol, sorbitol, PEG300, PEG2000 or sucrose, and preferably in the presence of water.

4. Wound dressing or method according to any of the preceding claims, wherein the coating (4, 8, 10) is able to guide and / or promote migration and / or proliferation of cells, wherein the cells are preferably cells involved in wound healing, more particularly fibroblasts or keratinocytes.

5. Wound dressing or method according to any of the preceding claims, wherein the coating (4, 8, 10) comprises - an alkyl radical, more particularly an alkyl radical having at least 8 carbon atoms, and / or - an alcohol, more particularly an alcohol having at least 8 carbon atoms, and / or - an amine, more particularly an amine having at least 8 carbon atoms, and / or - a fatty acid, more particularly a medium-chain or long-chain fatty acid, and / or - a constituent of an extracellular matrix, and / or - a denatured constituent of an extracellular matrix, more particularly gelatine, and / or - a coagulation factor, more particularly fibrinogen, and / or - a cell adhesion molecule, and / or - a synthetic polymer, more particularly polylysine, and / or - a sugar, more particularly an oligosaccharide or a polysaccharide, wherein the alcohol is preferably tridecan-1-ol, tetradecan-1-ol, pentadecan-1-ol, hexadecan-1-ol or octadecan-1-ol, wherein the fatty acid is preferably tridecanoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid, octadecanoic acid, oleic acid, linoleic acid or linolenic acid, wherein the constituent of an extracellular matrix is preferably elastin, entactin, fibronectin, hyaluronic acid, collagen, laminin or vitronectin, and wherein the cell adhesion molecule is preferably a cadherin, an integrin or a selectin.

6. Wound dressing or method according to any of the preceding claims, wherein the one or more lanes extend from an edge region of the wound-facing side of the wound contact layer (3) at least to a middle region (5) or central region (6) of the wound-facing side of the wound contact layer (3).

7. Wound dressing or method according to any of the preceding claims, wherein the one or more lanes form a lattice-like pattern (4, 8), star-shaped pattern or radiant pattern (10) on the wound-facing side of the wound contact layer (3).

8. Wound dressing or method according to any of the preceding claims, wherein the one or more lanes each have a width of 10 µm to 500 µm, preferably 10 µm to 400 µm, more preferably 10 µm to 300 µm, even more preferably 10 µm to 200 µm and very preferably 10 µm to 100 µm.

9. Wound dressing or method according to any of the preceding claims, wherein the coating (4, 8, 10) is present on a maximum of 10%, 20%, 30%, 40% or 50% of the area of the wound-facing side of the wound contact layer (3).

10. Wound dressing or method according to any of the preceding claims, wherein the coating (4, 8, 10) is produced by means of inkjet printing, which is preferably CIJ printing or DOD printing, more particularly DOD printing with multiple spray nozzles.

11. Wound dressing or method according to any of the preceding claims, wherein - the coating (4, 8, 10) penetrates partially into the wound contact layer (3) or - the coating (4, 8, 10) substantially does not penetrate into the wound contact layer (3), but is substantially merely supported on the wound contact layer (3).

12. Wound dressing or method according to any of the preceding claims, wherein - the coating (4, 8, 10) is chemically covalently bonded to the wound contact layer (3) or - the coating (4, 8, 10) is not chemically covalently bonded to the wound contact layer (3), but merely adheres to the wound contact layer (3).

13. Wound dressing or method according to any of the preceding claims, wherein - the wound contact layer (3) comprises a hydrogel or consists of a hydrogel and the coating (4, 8, 10) is applied to the wound contact layer (3) when the hydrogel is not yet completely crosslinked but is still reactive, so that the coating (4, 8, 10) can penetrate into the wound contact layer (3) and / or react with and chemically covalently bond to the wound contact layer (3), or - the wound contact layer (3) comprises a hydrogel or consists of a hydrogel and the coating (4, 8, 10) is applied to the wound contact layer (3) when the hydrogel is completely crosslinked and no longer reactive, so that the coating (4, 8, 10) cannot penetrate into the wound contact layer (3) and / or cannot react with and chemically covalently bond to the wound contact layer (3).

14. Wound dressing or method according to any of the preceding claims, wherein the wound dressing (1, 7, 9, 11, 13) further comprises a backing layer (2), more particularly a backing layer (2) composed of a polyurethane film, wherein the backing layer (2) preferably overhangs the wound contact layer (3) and forms an adhesive edge (14).

15. Wound dressing or method according to any of the preceding claims, wherein the wound dressing (11) further comprises an absorbent layer (12), more particularly an absorbent layer (12) composed of a polyurethane foam.