Microneedle dressing loaded with repair matrix

Abstract

The present disclosure describes a microneedle dressing carrying a repair matrix. The microneedle dressing includes a base layer and a microneedle layer. The base layer has a lower surface that faces the target surface when in use, and an upper surface opposite the lower surface. The microneedle layer includes a plurality of conical protrusions extending from the lower surface toward the target surface. The conical protrusions have a receiving portion for accommodating the repair matrix. The receiving portion is an annular groove that is concave from the outer wall of the conical protrusion. The repair matrix is ​​water-soluble and includes a first portion in the form of a dry powder and a second portion in the form of a film. The first portion is located within the receiving portion, and the second portion is disposed on the outer wall of the conical protrusion and completely covers the opening of the receiving portion. According to the present disclosure, a microneedle dressing can be provided that can stably carry a large amount of repair matrix and facilitates the rapid release of the repair matrix.

Description

Technical Field

[0001] The present invention generally relates to the field of biomedical engineering technology, and in particular to a microneedle dressing carrying a repair matrix. Background Art

[0002] Wound dressings are used to bandage wounds. They can carry medication to repair the wound surface during application. Traditional medical dressings typically sprinkle the medication on the surface facing the wound, allowing it to come into contact with the wound surface during application. Alternatively, the medication is adsorbed into an adsorption layer. When applied to the wound, the dressing absorbs exudate, allowing the medication to dissolve in the exudate and migrate to the wound surface through molecular diffusion between liquids.

[0003] However, the above methods can only bring the drug into contact with the wound surface, and are not effective in repairing deeper tissues, resulting in a longer recovery time for the wound surface. To solve this problem, the use of microneedles for transdermal delivery of macromolecular substances has gradually emerged in recent years. Specifically, microneedle dressings usually mix the drug with a molded and solidified component to make a microneedle-shaped drug. When applied, the drug microneedles are embedded in the wound and come into contact with the tissue fluid, dissolving and diffusing into the wound; or the microneedles are made of degradable / soluble substances, and the drug is loaded inside the microneedles. When applied, the drug gradually diffuses into the wound as the microneedles degrade / dissolve; or the drug is directly coated on the surface of the microneedles.

[0004] However, in the scheme of making the drug into the form of microneedles, the mixing of the drug and the molding and curing components may affect the repair performance of the drug; in the scheme of loading the drug inside the soluble microneedles, the release rate of the drug is affected by the dissolution rate of the soluble microneedles, and the soluble microneedles need to be dissolved before they can come into contact with the tissue fluid to repair the wound. Moreover, after the soluble microneedles are dissolved in the tissue fluid, the solubility saturation in the surrounding tissue fluid may be higher, which affects the repair efficiency of the drug; in the scheme of coating the drug on the surface of the microneedles, the amount of drug that can be carried is usually small, and the repair efficiency is too unsatisfactory. Summary of the Invention

[0005] In view of the above-mentioned existing situation, the present disclosure aims to provide a microneedle dressing that can stably carry a large amount of repair matrix and facilitates the rapid release of the repair matrix.

[0006] To this end, the present disclosure provides a microneedle dressing carrying a repair matrix, the microneedle dressing comprising a base layer and a microneedle layer, the base layer having a lower surface facing the target surface when in use, and an upper surface opposite to the lower surface, the microneedle layer comprising a plurality of conical protrusions from the lower surface toward the target surface, the conical protrusions having a receiving portion for accommodating the repair matrix, the receiving portion being an annular groove concave inward from the outer wall of the conical protrusion, the repair matrix being water-soluble, and the repair matrix comprising a first part in the form of dry powder and a second part in the form of a film, the first part being located in the receiving portion, and the second part being arranged on the outer wall of the conical protrusion and completely covering the opening of the receiving portion.

[0007] In the present disclosure, the microneedle dressing includes a base layer and a microneedle layer, the microneedle layer includes a plurality of conical protrusions facing the target surface, and the conical protrusions have a receiving portion for accommodating a repair matrix; the repair matrix includes a first part in the form of a dry powder and a second part in the form of a film. Compared with the repair matrix in the form of a liquid / gel, the concentration of effective active factors per unit volume of the repair matrix in the form of a dry powder is higher, and the shelf life of the bioactive substance is longer; the first part in the form of a dry powder can be loaded through the receiving portion on the conical protrusion, and the first part located in the receiving portion can be sealed by arranging the second part on the outer wall of the conical protrusion and completely covering the opening of the receiving portion, thereby facilitating the extension of the overall shelf life and also facilitating the increase of the total amount of the repair matrix carried by the microneedle dressing. In this case, when the target surface is a wound, the microneedle dressing of the present disclosure is applied to the wound. The microneedle layer can be embedded in the wound, and the membrane-like repair matrix located on the outer wall of the cone-shaped protrusion contacts and dissolves in the tissue fluid. The dry powdered first portion located in the receiving portion is exposed to the tissue fluid, allowing the first portion to quickly dissolve in the tissue fluid and diffuse to the surrounding area for repair. As a result, the microneedle dressing of the present disclosure can stably carry a large amount of repair matrix and facilitate the rapid release of the repair matrix.

[0008] In addition, in the microneedle dressing of the present disclosure, optionally, the conical protrusions are conical or pyramidal, with a cone angle of 15° to 75° and a height of 300μm to 1500μm. Furthermore, the multiple conical protrusions are arranged in an array, with a spacing of 300μm to 2000μm between two adjacent conical protrusions. In this case, the microneedle layer can be easily embedded in the wound during application, delivering the repair matrix to a predetermined depth below the wound surface. Furthermore, the dressing can have relatively uniform repair properties throughout, thereby ensuring a substantially uniform wound healing rate, which is beneficial to wound healing.

[0009] In addition, in the microneedle dressing of the present disclosure, optionally, the total area of ​​the plurality of conical protrusions, as projected along a direction perpendicular to the lower surface, accounts for 60% to 80% of the area of ​​the lower surface. In this case, the majority of the dressing area can be loaded with the repair matrix, thereby facilitating wound healing.

[0010] In addition, in the microneedle dressing of the present disclosure, optionally, there are multiple accommodating portions, and the multiple accommodating portions are arranged in sequence along the axial direction of the conical protrusion, thereby being able to accommodate more repair matrices.

[0011] Additionally, in the microneedle dressing of the present disclosure, optionally, in the axial cross-section of the conical protrusion, the inner contour of the receiving portion is generally U-shaped, and the inner wall of the receiving portion on the side closer to the cone tip of the conical protrusion is inclined from the inside to the outside toward the cone tip. In this case, when the microneedle dressing is applied to the wound, the inclined inner wall of the receiving portion can guide tissue fluid containing dissolved repair matrix to flow out of the receiving portion.

[0012] Additionally, in the microneedle dressing of the present disclosure, optionally, in an axial cross-section of the conical protrusion, the receiving portion can be considered to include a left half and a right half, with the portion of the conical protrusion between the left and right halves being referred to as a middle region, and the maximum depth of the annular groove being greater than the minimum width of the middle region. This allows the capacity of the receiving portion to be maximized while maintaining the mechanical strength of the conical protrusion, thereby accommodating a larger amount of repair matrix.

[0013] In addition, in the microneedle dressing of the present disclosure, the repair matrix optionally includes a supernatant of mesenchymal stem cells. The supernatant of the mesenchymal stem cells contains a substance that can promote wound healing. In this case, when the repair matrix contacts the wound, it can promote wound healing.

[0014] In addition, in the microneedle dressing of the present disclosure, optionally, the microneedle layer further comprises a substrate detachably bonded to the lower surface, the plurality of conical protrusions being provided on the substrate, and after administration, the microneedle layer is peeled off from the target surface and the base layer, and the base layer is applied to the target surface. In this case, peeling the microneedle layer from the wound after administration can remove the pressure on the wound caused by the conical protrusions, and peeling the microneedle layer from the base layer and applying the base layer to the wound surface can provide a good healing environment for the wound surface.

[0015] In addition, in the microneedle dressing involved in the present disclosure, optionally, the microneedle dressing also includes an intermediate layer with super hydrophilicity arranged on the side of the base layer opposite to the microneedle layer, and the base layer has a plurality of through holes penetrating the upper surface and the lower surface, and a super hydrophobic structure arranged on the lower surface. In this case, by providing a superhydrophobic structure on the lower surface, the lower surface can be made superhydrophobic. When the microneedle dressing with the microneedle layer removed is applied to the wound, the liquid on the second area of ​​the wound corresponding to the superhydrophobic structure can be at least partially retained, so that the second area is in a moist state and not soaked in liquid; the intermediate layer can absorb the liquid on the first area of ​​the wound corresponding to the through holes through the multiple through holes, thereby keeping the first area and the through holes dry. The cooperation between the intermediate layer and the base layer can effectively reduce the adverse effects of dead space on wound healing and provide a good healing environment for the wound; and when it is necessary to peel the dressing from the wound, since the second area is in a moist environment, the superhydrophobic property of the lower surface of the base layer can enable it to exhibit anti-adhesion properties to wound secretions and granulation tissue on the wound surface, etc., which can reduce the adhesion of the lower surface to the newly formed granulation tissue of the wound, making it easy to peel off from the wound, thereby avoiding secondary damage to the wound. Moreover, due to the spacing of the base layer, the dressing fibers of the intermediate layer are not easy to fall off to the wound, which can effectively reduce the foreign body reaction of the wound.

[0016] In addition, in the microneedle dressing disclosed herein, the interior of the intermediate layer optionally has varying water absorbency in the longitudinal direction, and the intermediate layer comprises a porous adsorption structure, and the repair matrix further comprises a third portion attached to the adsorption structure. Wounds at different stages require different healing environments. In this case, by varying the water absorbency of the interior of the intermediate layer in the longitudinal direction, an appropriate water absorbency can be selected based on the wound's healing status, providing a favorable healing environment for the wound. Furthermore, the repair matrix attached to the intermediate layer can dissolve in wound exudate absorbed by the intermediate layer and diffuse into the wound via the exudate, thereby promoting wound healing.

[0017] According to the present disclosure, a microneedle dressing can be provided that can stably carry a large amount of repair matrix and facilitates the rapid release of the repair matrix. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 is a schematic diagram illustrating a microneedle dressing according to an example of the present disclosure.

[0019] Figure 2 is a schematic diagram illustrating a microneedle layer according to an example of the present disclosure.

[0020] Figure 3 Schematic diagram showing a cone-shaped protrusion according to an example of the present disclosure.

[0021] Figure 4 Schematic diagram showing an axial cross section of a tapered protrusion according to an example of the present disclosure.

[0022] Figure 5 FIG. 1 is a schematic diagram showing another embodiment of a cone-shaped protrusion.

[0023] Figure 6 Schematic diagram showing a pyramidal protrusion carrying a repair matrix.

[0024] Figure 7 This is a schematic diagram of a cone-shaped protrusion embedded in the wound surface.

[0025] Figure 8 This is a schematic diagram of separating the microneedle layer from the basal layer and applying the remaining dressing to the wound surface.

[0026] Description of reference numerals:

[0027] 1…microneedle dressing, 10…microneedle layer, 11…conical protrusion, 111…cone tip, 12…substrate, 13…accommodation, 13a…left half, 13b…right half, 131…first accommodation, 132…second accommodation, 20…base layer, 21…lower surface, 22…upper surface, 23 through-hole, 30 middle layer, 40 top layer, 81…first part, 82…second part, 9…wound surface, 90…exudate layer, S1…first region, S2…second region. DETAILED DESCRIPTION

[0028] All references cited in this disclosure are incorporated by reference in their entirety as if fully set forth. Unless otherwise defined, technical and scientific terms used in this disclosure have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0029] The preferred embodiments of the present disclosure are described in detail below with reference to the accompanying drawings. In the following description, identical components are assigned identical reference numerals, and duplicate descriptions are omitted. In addition, the accompanying drawings are merely schematic, and the proportions of the dimensions of the components or the shapes of the components may differ from the actual ones.

[0030] The present disclosure relates to a microneedle dressing carrying a repair matrix, which can be used to protect and repair a target surface. The microneedle dressing carrying a repair matrix can be referred to as a "microneedle dressing" or "dressing," and can also be referred to as a medical dressing, trauma dressing, or wound dressing. The microneedle dressing of the present disclosure can stably carry a large amount of repair matrix and facilitate rapid release of the repair matrix within a wound.

[0031] In the present disclosure, the target surface may be a wound surface. A wound surface is damage caused by injury to normal skin (tissue), and may be, for example, a burn, abrasion, cut, sprain, ulcer, frostbite, or the like. In other words, the wound surface may refer to the surface of a wound. In other examples, the target surface may also be other surfaces, such as the skin surface.

[0032] Hereinafter, the microneedle dressing of the present disclosure will be described with reference to the accompanying drawings, taking the target surface as an example of a wound surface.

[0033] Figure 1 is a schematic diagram showing a microneedle dressing 1 according to an example of the present disclosure.

[0034] In this embodiment, the microneedle dressing 1 may include a base layer 20 and a microneedle layer 10 (see Figure 1 The base layer 20 may have a lower surface 21 that faces the target surface during use, and an upper surface 22 (shown later) opposite the lower surface 21. The microneedle layer 10 may be disposed on the lower surface 21 of the base layer 20, and the microneedle layer 10 may have a receiving portion 13 for accommodating a repair matrix (described in detail later). Thus, when the microneedle dressing 1 of the present disclosure is applied to the target surface, the repair matrix can be delivered into the tissue below the target surface through the microneedle layer 10.

[0035] Figure 2 is a schematic diagram showing a microneedle layer 10 according to an example of the present disclosure. Figure 3 is a schematic diagram showing a cone-shaped protrusion 11 according to an example of the present disclosure.

[0036] In some examples, the microneedle layer 10 may include conical protrusions 11 that face toward the target surface during use (see Figure 2 The conical protrusion 11 may have a receiving portion 13 for receiving the repair matrix (see Figure 3 Thus, when the microneedle dressing 1 is applied to the wound surface, the conical protrusions 11 can be embedded in the wound surface, and the repair matrix can be delivered to the tissue under the wound surface.

[0037] In some examples, the conical protrusions 11 may be provided on the lower surface 21. For example, the conical protrusions 11 may protrude from the lower surface 21 toward the target surface. When the microneedle dressing 1 is applied to the target surface, the lower surface 21 may be considered parallel to the target surface, and the cone axis of the conical protrusions 11 may be orthogonal to the lower surface 21.

[0038] In other examples, the microneedle layer 10 may further include a substrate 12, and the cone-shaped protrusions 11 may be disposed on the substrate 12 (see Figure 2The substrate 12 can be detachably bonded to the lower surface 21. After administration, the microneedle dressing 1 can be peeled from the wound surface, and the microneedle layer 10 can be peeled from the lower surface 21 of the base layer 20 by separating the substrate 12 from the lower surface 21. The base layer 20 can then be applied to the wound surface. In this case, peeling the microneedle layer 10 from the wound after administration can remove the pressure on the wound caused by the conical protrusions 11. Peeling the microneedle layer 10 from the base layer 20 and applying the base layer 20 to the wound surface can provide a good healing environment for the wound.

[0039] In some examples, there may be multiple conical protrusions 11, thereby being able to carry more repair matrices.

[0040] In some examples, the conical protrusions 11 can be conical or pyramidal. In some examples, the conical protrusions 11 can have a taper angle of 15° to 75° and a height of 300 μm to 1500 μm. This facilitates the insertion of the microneedle layer 10 into the wound during application, delivering the repair matrix to a predetermined depth below the wound surface. For example, the conical protrusions 11 can have a taper angle of 15°, 30°, 45°, 60°, or 75°.

[0041] In some examples, the plurality of conical protrusions 11 may be arranged in an array, and the distance between two adjacent conical protrusions 11 may be 300 μm to 2000 μm. In this case, the dressing can have relatively uniform repair properties, thereby making the wound healing speed substantially consistent and facilitating wound healing.

[0042] In some examples, the total area of ​​the plurality of pyramidal protrusions 11, as projected along a direction perpendicular to the lower surface 21, may account for 60% to 80% of the area of ​​the lower surface 21. For example, the total area of ​​the plurality of pyramidal protrusions 11 may account for 60%, 65%, 70%, 75%, or 80% of the area of ​​the lower surface 21. In this case, the majority of the dressing area can be loaded with the repair matrix, thereby facilitating wound healing.

[0043] In some examples, the receiving portion 13 may be an annular groove that is recessed from the outer wall of the conical protrusion 11 (see Figure 3 ). Thus, the repair matrix can be accommodated through the annular groove.

[0044] Figure 4 Schematic diagram showing an axial cross section of the conical protrusion 11 according to an example of the present disclosure. Figure 4 In FIG. 1 , line L schematically represents the axis (center line) of the conical protrusion 11 .

[0045] In some examples, in the axial section of the conical protrusion 11, the receiving portion 13 can be considered to include a left half 13a and a right half 13b (see Figure 4The inner contours of the left half 13a and the right half 13b may be roughly U-shaped. In other words, the accommodating portion 13 may be roughly U-shaped. This facilitates accommodating the repair matrix.

[0046] In some examples, on the axial cross section of the conical protrusion 11, the inner wall of the receiving portion 13 on the side closer to the cone tip 111 of the conical protrusion 11 may be inclined from the inside to the outside toward the cone tip 111. Figure 4 The inner wall of the left half 13a on the side closer to the cone tip 111 is inclined along the direction D1 toward the direction closer to the cone tip 111, forming a smooth curve. Figure 4 The inner contour shown also falls within the range of "roughly U-shaped" as described above. In this case, when the microneedle dressing 1 is applied to the wound surface, the inclined inner wall of the receiving portion 13 can guide the tissue fluid containing the dissolved repair matrix to flow out of the receiving portion 13.

[0047] In some examples, on the axial cross section of the conical protrusion 11 , the inner contours of the left half 13 a and / or the right half 13 b may also be substantially semicircular.

[0048] In some examples, the portion of the conical protrusion 11 between the left half 13a and the right half 13b is referred to as the middle region, and the maximum depth of the annular groove may be greater than the minimum width of the middle region. The maximum depth of the annular groove may refer to the maximum length from the center of the opening of the annular groove to its inner contour, see Figure 4 The maximum depth d of the annular groove is greater than the minimum width c of the middle region. Thus, the capacity of the receiving portion 13 can be expanded as much as possible while ensuring the mechanical strength of the conical protrusion 11, thereby accommodating more repair matrix.

[0049] In some examples, the volume of the accommodation space of the accommodation portion 13 may account for 15% to 60% of the total volume of the conical protrusion 11. Thus, while the conical protrusion 11 has suitable mechanical strength to be embedded in the wound surface, the accommodation portion 13 can accommodate as much repair matrix as possible, thereby facilitating wound recovery.

[0050] Figure 5 FIG. 1 is a schematic diagram showing another embodiment of the conical protrusion 11 .

[0051] In some examples, there are multiple accommodating portions 13, and the multiple accommodating portions 13 are arranged in sequence along the axial direction of the conical protrusion 11. Figure 5 In the example shown, the number of the accommodating portions 13 may be two (ie, a first accommodating portion 131 and a second accommodating portion 132), and the first accommodating portion 131 and the second accommodating portion 132 may be sequentially arranged along the axial direction of the conical protrusion 11. Thus, more repair matrix can be accommodated.

[0052] In some examples, when there are multiple receiving portions 13, the depth of each receiving portion 13 can be adaptively reduced, maintaining a certain ratio between the total volume of the receiving spaces of all receiving portions 13 and the volume of the conical protrusion 11 while ensuring the mechanical strength of the conical protrusion 11. In this case, the total amount of repair matrix contained in the receiving portions 13 remains unchanged or may even increase. However, the reduced depth of the receiving portions 13 can accelerate the diffusion of the repair matrix from the receiving space to the outside during application, thereby facilitating rapid release of the repair matrix and shortening drug administration time.

[0053] Figure 6 Schematic diagram showing the conical protrusion 11 carrying the repair matrix.

[0054] In some examples, the repair matrix can be a water-soluble material, so that it can dissolve in tissue fluid and diffuse to the surrounding area to repair the wound.

[0055] In some examples, the repair matrix may include a first portion 81 in the form of dry powder and a second portion 82 in the form of a film. The first portion 81 may be located within the receiving portion 13, and the second portion 82 may be disposed on the outer wall of the conical protrusion 11 and completely cover the opening of the receiving portion 13 (see Figure 6 Compared to a repair matrix in liquid / gel form, a repair matrix in the form of a dry powder has a higher concentration of effective active factors per unit volume and a longer shelf life of the bioactive substances. In this case, the first portion in the form of a dry powder is loaded into the receiving portion 13, and the second portion 82 is arranged on the outer wall of the conical protrusion 11 and completely covers the opening of the receiving portion 13. This can seal the first portion located in the receiving portion 13, thereby extending the overall shelf life and increasing the total amount of the repair matrix carried by the microneedle dressing 1.

[0056] In the present disclosure, the repair matrix refers to a substance that can repair the wound / wound surface, that is, a substance that can promote wound recovery, and can also be called a drug.

[0057] In some examples, the film-shaped second portion 82 may completely cover the outer wall of the conical protrusion 11 .

[0058] Figure 7 It is a schematic diagram of the cone-shaped protrusion 11 embedded in the wound surface 9. Figure 7 The arrows in the figure schematically indicate the diffusion direction of the repair matrix.

[0059] When the microneedle dressing 1 is applied to the wound surface 9, the microneedle layer 10 can be embedded in the wound surface 9, such as Figure 7As shown, the majority of the conical protrusion 11 is located below the wound surface 9. The membrane-like repair matrix (second portion 82) on the outer wall of the conical protrusion 11 contacts and dissolves in the tissue fluid, exposing the dry powdered repair matrix (first portion 81) within the receiving portion 13 to the tissue fluid. This allows the first portion 81 to quickly dissolve in the tissue fluid and diffuse to the surrounding area for repair. Thus, the microneedle dressing 1 disclosed herein can stably carry a large amount of repair matrix and facilitates its rapid release.

[0060] In some examples, after applying the microneedle dressing 1 to the wound, it takes 1 to 3 hours for the drug to completely dissolve in the exudate. After administration (i.e., after the drug has dissolved), the microneedle dressing 1 can be removed from the wound. The time it takes for the drug to dissolve in the exudate also depends on the type of drug.

[0061] In some examples, the repair matrix can include mesenchymal stem cells and / or mesenchymal stem cell derivatives. For example, in some examples, the repair matrix can include a supernatant of mesenchymal stem cells. The supernatant of mesenchymal stem cells contains substances that can promote wound healing. In this case, when the repair matrix contacts the wound, it can facilitate wound healing.

[0062] In some examples, the supernatant of mesenchymal stem cells can include mesenchymal stem cell-derived exosomes. Exosomes are extracellular vesicles secreted by cells and containing complex RNA and proteins. In this case, mesenchymal stem cell-derived exosomes can promote wound healing through paracrine effects, inhibiting wound inflammatory responses, promoting angiogenesis, improving the extracellular matrix environment, and mobilizing the body's own cells to migrate to the site of injury, thereby repairing the wound.

[0063] In some examples, the supernatant of mesenchymal stem cells may also include one or more of vascular endothelial growth factor, epidermal growth factor, transforming growth factor-β, liver growth factor, superoxide dismutase, interleukin-6, collagen, fibronectin, and platelet-derived factor. In this case, wound healing can be promoted by repairing the matrix.

[0064] In some examples, the supernatant of mesenchymal stem cells can include one or more of mesenchymal stem cell exosomes, vascular endothelial growth factor, epidermal growth factor, transforming growth factor-β, liver growth factor, superoxide dismutase, interleukin-6, collagen, fibronectin, and platelet-derived factor. In this case, the repair ability of the repair matrix can be further enhanced, thereby promoting wound healing.

[0065] The present disclosure is not limited thereto, and the corresponding repair matrix can be selected according to the actual situation of the wound. For example, in some examples, the repair matrix can also include other components that help wound healing. For example, the repair matrix can also include hemostatic powder, etc.

[0066] In some examples, the mesenchymal stem cells can be umbilical cord mesenchymal stem cells, bone marrow mesenchymal stem cells, or adipose-derived mesenchymal stem cells. The repair matrix can include a variety of mesenchymal stem cells and / or derivatives of mesenchymal stem cells. That is, in some examples, the repair matrix can include derivatives of one or more of umbilical cord mesenchymal stem cells, bone marrow mesenchymal stem cells, and adipose-derived mesenchymal stem cells. In this case, all types of mesenchymal stem cells and their derivatives can be beneficial to wound healing, and are abundant in source, and the composition of the repair matrix can be easily adjusted according to actual needs.

[0067] Figure 8 Schematic diagram of separating the microneedle layer 10 from the base layer 20 and applying the remaining dressing to the wound surface. Figure 8 , a schematic cross-sectional view of the base layer 20, the middle layer 30 and the top layer 40 is shown, and arrows schematically indicate the movement direction of the exudate during application.

[0068] In some examples, the base layer 20 may have a plurality of through holes 23 extending through the upper surface 22 and the lower surface 21 (see FIG. Figure 8 In some examples, a super-hydrophobic structure may be provided on the lower surface 21 of the substrate layer 20. Thus, the lower surface 21 can be made super-hydrophobic. In the present disclosure, super-hydrophobicity refers to a surface having a water droplet contact angle greater than 150° and a rolling angle less than 10°. In other words, by providing a super-hydrophobic structure on the lower surface 21, the water droplet contact angle on the lower surface 21 can be made greater than 150° and the rolling angle less than 10°.

[0069] It is understood that the super-hydrophobic structure is an unperforated area provided on the lower surface 21. In some examples, the super-hydrophobic structure may include a plurality of micron-sized protrusions spaced apart on the lower surface 21, and nanoparticles provided on the surfaces of the micron-sized protrusions. In this case, by providing a plurality of micron-sized protrusions and nanoparticles on the lower surface 21 of the base layer 20, when a liquid droplet contacts the lower surface 21, due to the presence of the micron-sized protrusions and nanoparticles, an air film is formed between the liquid droplet and the lower surface 21, hindering the liquid from wetting the lower surface 21, thereby forming a super-hydrophobic state and making the lower surface 21 super-hydrophobic.

[0070] In some examples, the microneedle dressing 1 further includes an intermediate layer 30 disposed on the base layer 20 (see Figure 8). The intermediate layer 30 is located on the side of the base layer 20 opposite to the microneedle layer 10. That is, the intermediate layer 30, the base layer 20, and the microneedle layer 10 are stacked in sequence. The intermediate layer 30 may have super hydrophilicity. In this case, the super hydrophobic structure provided on the lower surface 21 can make the lower surface 21 have super hydrophobic properties, see Figure 8 When the microneedle dressing 1 with the microneedle layer 10 removed is applied to the wound surface 9 having the liquid permeable layer 90 on the surface, the liquid on the second area S2 of the wound surface 9 corresponding to the superhydrophobic structure can be at least partially retained, so that the second area S2 is in a moist state and not soaked in liquid; the intermediate layer 30 can absorb the liquid on the first area S1 of the wound surface 9 corresponding to the through holes 23 through the multiple through holes 23, thereby keeping the first area S1 and the through holes 23 dry. The cooperation between the intermediate layer 30 and the base layer 20 can effectively reduce the adverse effects of dead space on wound healing, and also It can provide a good healing environment for the wound surface 9; and when the dressing needs to be peeled off from the wound surface 9, since the second area S2 is in a moist environment, the superhydrophobic property on the lower surface 21 of the base layer 20 can enable it to exhibit anti-adhesion properties to wound secretions and granulation tissue on the wound surface, etc., which can reduce the adhesion of the lower surface 21 to the newly formed granulation tissue of the wound, making it easy to peel off from the wound surface 9, thereby avoiding secondary damage to the wound, and due to the spacing of the base layer 20, the dressing fibers of the intermediate layer 30 are not easy to fall off to the wound surface 9, which can effectively reduce the foreign body reaction of the wound.

[0071] Among them, those skilled in the art will understand that keeping the first area S1 and the through-hole 23 dry can refer to a relatively dry environment; specifically, under normal circumstances, the adsorption of exudate by the intermediate layer 30 can keep the first area S1 and the through-hole 23 dry. It should be noted that in some cases, due to the spacing of the base layer 20, the first area S1 and the intermediate layer 30 are not in contact, and some liquid on the surface of the first area S1 (for example, some liquid on the first area S1 that is not in the through-hole 23) may not be absorbed by the intermediate layer 30 in time. As this part of the liquid increases and flows toward the vicinity of the through-hole 23, it will still be absorbed by the intermediate layer 30. This situation also falls within the scope of "keeping the first area S1 and the through-hole 23 dry" as stated in the present disclosure, that is, the adsorption by the intermediate layer 30 can at least maintain a dry environment in the through-hole 23.

[0072] In other words, in the present disclosure, the adsorption of the intermediate layer 30 not only maintains the wettability of the wound surface 9, but also effectively prevents the adverse effects of dead space on wound healing. Furthermore, in the present disclosure, the intermediate layer 30 absorbs excess exudate, keeping the wound surface 9 moist but not soaked in liquid, thus providing an optimal healing environment for the wound surface 9. In the present disclosure, the superhydrophilicity of the intermediate layer 30 means that the contact angle between a water droplet and the surface of the intermediate layer 30 is close to 0°, making the intermediate layer 30 extremely easily wetted.

[0073] In some examples, the through holes 23 on the base layer 20 may be cylindrical. That is, the through holes 23 have the same pore diameter on the upper surface 22 and the lower surface 21. In this case, the intermediate layer 30 can easily absorb liquid on the target surface through the through holes 23.

[0074] In some examples, a super-hydrophobic structure may be provided on the inner wall of the through hole 23. In this case, it is possible to reduce the amount of liquid hanging on the inner wall of the through hole 23, which is beneficial to maintaining the dryness in the through hole 23.

[0075] In some examples, the thickness of the base layer 20 can be 0.1 mm to 2 mm. It should be noted that in this disclosure, the thickness of the base layer 20 includes the thickness of the micron-sized protrusions and the total thickness of the nanoparticles. In this case, the base layer 20 is of moderate thickness, maintaining good air permeability and facilitating the absorption of liquid from the target surface by the intermediate layer 30 through the through holes 23. In some examples, preferably, the thickness of the base layer 20 can be 0.1 mm to 1 mm.

[0076] In some examples, the thickness of the middle layer 30 can be 0.5 mm to 5 mm. In this case, the middle layer 30 has good air permeability and water absorption, which can be beneficial to providing a good healing environment.

[0077] In some examples, the interior of the intermediate layer 30 may have varying water absorbencies along the longitudinal direction. Wounds at different stages require different healing environments (described later). In this case, by configuring the intermediate layer 30 to have varying water absorbencies along the longitudinal direction, an appropriate water absorbency can be selected based on the wound's healing status, providing a favorable healing environment for the wound.

[0078] In some examples, the intermediate layer 30 has an inner surface facing the base layer 20 and an outer surface opposite the inner surface. The longitudinal direction may refer to a direction perpendicular to the inner surface and the outer surface.

[0079] In some examples, the water absorption of the middle layer 30 can be gradually increased from the inner surface to the outer surface. For ease of description, the portion of the middle layer 30 relatively close to the upper top layer 40 is referred to as the upper layer, and the portion relatively close to the upper top layer 40 is referred to as the lower layer (this does not mean that the middle layer 30 of the present disclosure only includes two clearly separated layers). In the early stage of wound formation, the wound secretes a large amount of exudate. In this case, when the microneedle dressing 1 is applied to the wound in the early stage, the exudate from the wound moves from the through hole 23 to the lower layer of the intermediate layer 30 and is absorbed by the lower layer. Compared with the intermediate layer 30 with the same water absorption of the upper and lower layers, since the water absorption of the upper layer of the intermediate layer 30 in this example is greater than that of the lower layer, most of the exudate inside the lower layer tends to diffuse toward the upper layer, and only a small part will diffuse laterally in the lower layer. At this time, the unsaturated lower layer will continue to quickly absorb the exudate in the first area S1 and the through hole 23. Thus, the excess exudate on the wound can be quickly absorbed through the intermediate layer 30, and the relatively low hydrophilic area of ​​the lower layer helps to form an air cavity that separates the adsorbed liquid and the wound, which can provide a good healing environment for the wound in the early stage.

[0080] In other examples, the water absorption of the intermediate layer 30 may also gradually decrease from the inner surface to the outer surface. In the middle and late stages of wound formation, the wound secretes less exudate, and some areas of the wound may have scabs. In this case, by configuring the water absorption of the lower layer of the intermediate layer 30 to be stronger than that of the upper layer, when the microneedle dressing 1 is applied to the wound in the middle and late stages, the exudate on the wound surface is absorbed by the lower layer of the intermediate layer 30 through the through holes 23. Most of the exudate in the lower layer tends to diffuse laterally within the lower layer, and most of the exudate is retained in the lower layer of the intermediate layer 30, which can keep the first area S1 on the wound surface in a humid ambient air state, thereby providing a good healing environment for the wound in the middle and late stages.

[0081] In some examples, the water absorption of the intermediate layer 30 can exhibit a gradient, increasing or decreasing from the inner surface to the outer surface. Specifically, for an intermediate layer 30 with a thickness of 3 mm and a gradually increasing water absorption from the inner surface to the outer surface, the intermediate layer 30 is divided into three 1 mm thick layers, namely the first layer, the second layer, and the third layer, from the inner surface to the outer surface. The water absorption within each layer is consistent, and the water absorption of each layer satisfies the following: water absorption of the first layer < water absorption of the second layer < water absorption of the third layer. This facilitates the preparation of intermediate layers 30 with varying water absorption.

[0082] In some examples, the early stage of wound appearance may refer to the first three days after the wound appears, and the mid-to-late stage may refer to the period three days after the wound appears. Of course, it should be noted that due to the different physical conditions of each patient, the degree of wound recovery may vary even after the same period of time, and different configurations of the intermediate layer 30 may be selected based on the amount of exudate secreted by the wound. Specifically, wound healing can generally be divided into four stages: coagulation stage, inflammation stage, repair stage, and maturation stage. The early stage of wound appearance in the present disclosure may refer to the stage when the wound is in the coagulation stage and / or inflammation stage, and the mid-to-late stage may refer to the stage when the wound is in the repair stage and / or maturation stage.

[0083] In some examples, the middle layer 30 may include an upper layer relatively close to the top layer 40 and a lower layer relatively close to the base layer 20. In some examples, the upper layer may have a higher water absorption than the lower layer. This can provide a favorable healing environment for wounds in the early stages. In other examples, the upper layer may have a lower water absorption than the lower layer. This can provide a favorable healing environment for wounds in the middle and late stages.

[0084] In some examples, the middle layer 30 may further include a transition layer between the upper layer and the lower layer, wherein the water absorption of the transition layer is between the water absorption of the upper layer and the water absorption of the lower layer.

[0085] In some examples, the portions of the intermediate layer 30 with different water absorption properties can be made of different materials or have different structures. This allows for different water absorption properties within the intermediate layer 30. In some examples, the water absorption properties of the intermediate layer 30 can be adjusted by varying the density of the mesh structure within the intermediate layer 30. For example, increasing the density of the mesh structure can improve the water absorption properties of the corresponding region.

[0086] In some examples, the intermediate layer 30 may comprise an adsorption structure. The repair matrix may further comprise a third portion attached to the adsorption structure. In this case, the repair matrix attached to the intermediate layer 30 can dissolve in wound exudate absorbed by the intermediate layer 30 and diffuse into the wound surface through the exudate, thereby promoting wound healing. In some examples, the third portion of the repair matrix may also be in the form of a freeze-dried powder. This can facilitate wound healing.

[0087] In some examples, the adsorption structure can be porous, and the repair matrix can be attached to the adsorption structure. In this case, during the process of the middle layer 30 adsorbing the exudate through the through hole 23, the water-soluble repair matrix dissolves in the exudate and diffuses to the wound surface through the exudate, thereby facilitating the healing of the wound surface. In other words, the repair matrix can be releasably attached to the adsorption structure. When the repair matrix is ​​not in contact with the liquid, it can be attached to the adsorption structure. When the repair matrix contacts the liquid, it can dissolve in the liquid and undergo molecular diffusion movement in the liquid (i.e., released by the adsorption structure).

[0088] In some examples, the microneedle dressing 1 may further include an upper top layer 40 disposed on the middle layer 30 (see Figure 8 ). The top layer 40 can be located on the side of the intermediate layer 30 opposite to the base layer 20. The top layer 40 can be hydrophobic. In this case, the top layer 40 can effectively prevent pollutants in the external environment (especially liquids that may carry bacteria / germs) from entering the dressing, acting as a barrier, thereby reducing the risk of infection on the wound surface. In some examples, the top layer 40 can be a silicone rubber film, also known as a PDMS (polydimethylsiloxane) film. In this case, the top layer 40 is soft and has good air permeability, which can provide a good healing environment for the wound surface.

[0089] In some examples, the surface of the top layer 40 facing the middle layer 30 and the surface opposite to the top layer 40 may each be provided with a superhydrophobic structure. In this case, the hydrophobicity of both surfaces of the top layer 40 can be enhanced, thereby inhibiting the evaporation of exudate within the middle layer 30, thereby providing a suitable moist environment for the wound surface. In addition, the top layer 40 can further enhance its anti-contamination performance, reducing the risk of infection on the wound surface.

[0090] In some examples, the layers may be bonded to each other by an adhesive. In some examples, an adhesive may be applied to the peripheral region between the base layer 20 and the substrate 12 of the microneedle layer 10 to allow the base layer 20 and the substrate 12 to be detachably bonded to each other.

[0091] In some examples, the base layer 20, the middle layer 30, and the top layer 40 may be in a sheet shape, which can facilitate the microneedle dressing 1 to cover the target surface.

[0092] In some examples, the microneedle dressing 1 may be in the form of a long roll. When used, the microneedle dressing 1 may be cut into a desired size (e.g., a shape that can cover the wound surface) before use.

[0093] In some examples, the microneedle dressing 1 can be attached to the wound surface using medical tape. Alternatively, both ends of the top layer 40 can be directly extended outward, and adhesive is applied to the inner walls of the two ends of the top layer 40 extending outward, thus forming a bandage, thereby allowing the microneedle dressing 1 to be attached to the wound surface.

[0094] In some examples, the microneedle dressing 1 further includes a protective film that releasably covers the microneedle layer 10. In this case, the protective film can be provided to keep the microneedle layer 10 clean before use. When use is required, the protective film can be peeled off from the microneedle layer 10.

[0095] In some examples, the protective film can be a flexible sponge rubber. In this case, the protective film can adapt to the shape of the microneedle layer 10 to better protect it.

[0096] In some examples, the microneedle dressing 1 further includes a second protective film that releasably covers the surface of the top layer 40 that is relatively remote from the middle layer 30. In this case, the second protective film can be provided to maintain the surface of the top layer 40 that is relatively remote from the middle layer 30 in a clean state before use. When the microneedle dressing 1 needs to be attached to the wound surface, the second protective film is peeled off from this surface, thereby reducing the impact on the air permeability of the top layer 40.

[0097] In some examples, the protective film and / or the second protective film may also be release paper, thereby enabling effective protection.

[0098] According to the microneedle dressing 1 involved in the present disclosure, a large amount of repair matrix can be stably carried, and it is beneficial for the rapid release of the repair matrix in the wound.

[0099] Although the present disclosure has been described in detail above with reference to the accompanying drawings and embodiments, it will be understood that the above description does not limit the present disclosure in any form. Those skilled in the art may modify and change the present disclosure as needed without departing from the spirit and scope of the present disclosure, and such modifications and variations all fall within the scope of the present disclosure.

Claims

1. A microneedle dressing carrying a repair matrix, characterized by: The microneedle dressing comprises a base layer and a microneedle layer, wherein the base layer has a lower surface facing the target surface when in use, and an upper surface opposite to the lower surface. The microneedle layer includes a plurality of conical protrusions extending from the lower surface toward the target surface, each conical protrusion having a receiving portion for receiving the repair matrix, wherein the receiving portion is an annular groove concave from the outer wall of the conical protrusion, and the inner wall of the receiving portion on the side closer to the cone tip of the conical protrusion is inclined from the inside to the outside toward the cone tip, and the volume of the receiving space of the receiving portion accounts for 15% to 60% of the total volume of the conical protrusion; The repair matrix is ​​water-soluble and includes a first part in dry powder form and a second part in film form. The first part is located in the accommodation portion, and the second part is arranged on the outer wall of the conical protrusion and completely covers the opening of the accommodation portion.

2. The microneedle dressing according to claim 1, wherein: The conical protrusions are conical or pyramidal, with a cone angle of 15° to 75° and a height of 300 μm to 1500 μm. The multiple conical protrusions are arranged in an array, and a distance between two adjacent conical protrusions is 300 μm to 2000 μm.

3. The microneedle dressing according to claim 1, wherein: In a projection along a direction normal to the lower surface, a total area of ​​the plurality of cone-shaped protrusions accounts for 60% to 80% of an area of ​​the lower surface.

4. The microneedle dressing according to claim 1, wherein: There are multiple accommodating portions, and the multiple accommodating portions are arranged in sequence along the axial direction of the conical protrusion.

5. The microneedle dressing according to claim 1, wherein: On the axial cross section of the conical protrusion, the inner contour of the accommodating portion is substantially U-shaped.

6. The microneedle dressing according to claim 1 or 5, characterized in that: On the axial section of the conical protrusion, the accommodating portion can be considered to include a left half and a right half, and the portion of the conical protrusion located between the left half and the right half is called the middle area, and the maximum depth of the annular groove is greater than the minimum width of the middle area.

7. The microneedle dressing according to claim 1, wherein: The repair matrix includes the supernatant of mesenchymal stem cells.

8. The microneedle dressing according to claim 1, wherein: The microneedle layer also includes a substrate detachably bonded to the lower surface, and the multiple conical protrusions are arranged on the substrate. After drug administration, the microneedle layer is peeled off from the target surface and peeled off from the base layer, and the base layer is applied to the target surface.

9. The microneedle dressing according to claim 8, wherein: The microneedle dressing further includes a super-hydrophilic intermediate layer disposed on a side of the base layer opposite to the microneedle layer. The base layer has a plurality of through holes penetrating the upper surface and the lower surface, and a super-hydrophobic structure disposed on the lower surface.

10. The microneedle dressing according to claim 9, wherein: The interior of the intermediate layer has different water absorption in the longitudinal direction, and the intermediate layer has a porous adsorption structure. The repair matrix further includes a third part attached to the adsorption structure.

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