Brushed wound dressing

Abstract

The present invention relates to an absorbent hemostatic patch utilizing a meltblown, brushed or loosened biocompatible fibrous fabric substrate that is thin, highly flexible, strong and porous, suitable for coating with cross-linking active molecules, and ultimately effective for use as a hemostatic agent in problematic bleeding situations.

Description

[Background technology]

[0001] Absorbable hemostatic patches containing two crosslinkable components are described in the literature, including U.S. Patent Application Publication No. 2011 / 0045047(A1). The crosslinkable components for such patches may be a pair of coreactive compounds, or a substrate coated with a coreactive compound having available units capable of forming covalent crosslinks with corresponding coreactive groups on the substrate. Plasma-derived biological components that initiate, enhance, and / or support the hemostatic cascade toward fibrin thrombus formation have also been applied to substrates of various structures and materials. [Overview of the project] [Means for solving the problem]

[0002] The present invention relates to an absorbable hemostatic patch for sealing, and more specifically, to an economically viable elastic layer nonwoven matrix substrate composed of meltblown microfibers, with a surface that is napped or loosened for high tissue adhesion. The napped substrate has an unparalleled high surface area and is suitable for coating with crosslinkable active molecules (e.g., PEG) in the development of high-performance, thin hemostatic patches, which would otherwise lack excellent tissue adhesion properties.

[0003] The present invention relates to absorbable hemostatic nonwoven patches and wound dressings utilizing a melt-blown, surface-brushed or loosened biocompatible fiber fabric substrate, which is thin, highly flexible, strong, and porous, suitable for coating with crosslinkable active molecules, and ultimately effective as a hemostatic agent in problematic bleeding situations. [Brief explanation of the drawing]

[0004] [Figure 1] This is a schematic exploded view of an independent meltblown patch in which the surface fibers are lifted and the matrix loft is increased by the napping method. [Figure 2]This figure shows a cross-sectional image of a substrate comparing a non-napped substrate with a substrate with a different degree of nappiness. [Figure 3] This figure shows airborne (left) and cross-sectional (right) SEM images of uniformly coated non-napped (top) and napped (bottom) substrates. [Figure 4] This figure shows images of uniformly coated non-napped (top) and napped (bottom) substrates obtained using micro-CT. [Modes for carrying out the invention]

[0005] The present invention relates to a matrix particularly suitable for coating, as the napped surface increases the surface area for coating individual meltblown fibers in the nonwoven matrix. A preferred high matrix loft is generated by a napping process, which loosens tightly entangled fibers, increases the matrix loft and overall volume, and can increase the penetration depth of the coating layer applied later.

[0006] One advantage of the present invention is that the resulting wound dressing is sided, as the napped surface can be easily identified as the napped and coated surface to be applied to the tissue surface.

[0007] The wound dressing of the present invention exhibits strong patch adhesion to tissue because the amount of fibers coated on the napped surface is increased and the surface roughness is increased, both of which strengthen adhesion at the interface between the patch and the tissue.

[0008] Another advantage of the present invention is that it is a thin patch that is easy to handle, has relatively low thickness and density, does not impair functionality when napped, and can be easily handled in a smaller space. The patch may also need to reduce the compression time for sealing.

[0009] Another advantage of the present invention is that the degree of napping can be adjusted to control specific properties, such as reducing stiffness as the degree of napping increases.

[0010] The wound dressing of the present invention exhibits high tissue compatibility because the combination of the elastic layer and the rough matrix enables high tissue compatibility when the tissue expands or moves.

[0011] In one embodiment, the meltblown nonwoven matrix can be manufactured using biocompatible and absorbable materials, for example, by adjusting the fiber diameter and polymer structure during pre-irradiation and / or melt extrusion and crystallization, respectively, so that the present invention can be manufactured to have controlled absorption time / biocompatibility.

[0012] In one embodiment, the nonwoven substrate is produced by extruding an absorbent and biocompatible polyester material, such as Monocryl®, a copolymer of glycolide and epsilon-caprolactone, through a linear die containing hundreds of small orifices. A converging flow of high-temperature air thins the molten polymer to form very fine diameter fibers. High-speed air blows the fibers onto a collection drum to form a single meltblown nonwoven fabric. Process factors such as drum speed and the distance between the drum and the die surface are selected to obtain a desirable fiber diameter and fiber orientation on the formed web, which governs the resulting fiber diameter, pore size, and density of the nonwoven matrix.

[0013] The drum size is arbitrary, depending on the length of the polymer extrusion die, and can be scaled up for large-scale production of meltblown sheets. Drum speed is inversely proportional to the nonwoven matrix density per unit area and is essentially related to fiber diameter, specific surface area, and overall porosity in the layer. The distance from the collector also affects the matrix properties, as increasing the gap between the polymer extrusion die and the drum makes the fiber thickness and orientation more random.

[0014] The present invention specifies preferred drum speeds in the range of 0.08 to 0.41 m / s, more preferably 0.12 to 0.37 m / s, and most preferably 0.15 to 0.2 m / s, and distances in the range of 10 to 40 inches, more preferably 15 to 35 inches, and most preferably 20 to 30 inches, in order to prepare and produce microporous, water-impermeable, and thin (thick) nonwoven films.

[0015] These ranges were established using Monocryl®, and material properties (e.g., intrinsic viscosity of 1.67) may have a slight influence on the properties of the fibers, consequently affecting the porosity, density, and stiffness of the entire matrix. However, these ranges should show the same trend regardless of material details (for example, increasing the drum speed reduces the patch density of both Monocryl® and Vicryl®, Polygratin 910, and polyglycolic acid, and at least the determined ranges are a viable starting point). Biodegradable polymers that can be meltblown include, but are not limited to, polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), polydioxanone (PDS), and caprolactone / glycolide polyesters such as poly(caprolactone-co-glycolide).

[0016] The present invention identified a preferred thickness in the range of 0.30 to 1.5 mm, more preferably 0.6 to 0.95 mm, and most preferably 0.85 to 0.90 mm, before napping. While this starting thickness may vary, after napping, the present invention confirmed a preferred increase in matrix height in the range of approximately 50 to 250%, more preferably 55 to 175%, and most preferably 125 to 165% of the original thickness.

[0017] This invention relates to a concentration of 140-250 mg / cm³. 3 More preferably 140-200 mg / cm³ 3, most preferably in the range of 140 - 150 mg / cm 3 of the preferred density was specified. The density is not expected to change significantly after raising the nap.

[0018] Based on micro-CT analysis, the present invention specified a preferred pore size distribution in the range of 0.01 - 0.5 mm, and most of the pores were in the range of 0.1 - 0.3 mm. Further, from the micro-CT analysis, the present invention specified that the total open porosity of the matrix is about 85%.

[0019] Melt-blowing these polymers provides unique advantages in generating ultrafine fibers. The melt-blown nonwoven fabric of the present invention specified fine fibers having a diameter in the range of 1 - 250 micrometers, preferably in the range of 1 - 90 microns.

[0020] In one embodiment, prior to raising the nap, an independent melt-blown patch is produced by extruding another sheet of melt-blown polyester-based nonwoven fabric onto a collecting drum, and then crystallizing the former sheet. A plurality of individual sheets are deposited on the drum to form a multilayer matrix. Next, the surface is modified by raising the nap to increase the surface area and the one-sidedness for coating. The raising effect is achieved by mechanically lifting the ends of the fibers on the surface of the patch using a polishing technique, and at the same time increasing the matrix loft as the entanglement of the fibers below the surface is loosened from the process.

[0021] Current napping methods utilize both manual and automatic tools. For manual napping, a steel file card (e.g., 3.75 inches) is used to brush the surface of the nonwoven fabric several times in one direction until the fibers begin to peel from the surface (5–15 strokes is a preferred working range in this method). For automatic napping, a benchtop drill press is used with a crimp wire wheel attachment (e.g., 0.25-inch stem, 3-inch diameter). Other instruments such as glass, wire brushes, and polishing flap wheels can also be used to achieve varying degrees of napping. Furthermore, compressed air, vacuum, or water jets can be used to loosen the matrix. To achieve extensive napping without destructive abrasion, the matrix can be exposed to heat before brushing to soften the fibers. Napping increases the cross-sectional area and specific surface area for coating cross-linkable active molecules (Figure 1), which ultimately provides the potential for superior structural integration between the hemostatic patch and tissue to enhance adhesion.

[0022] The degree of napping can be characterized by measuring the increased cross-sectional height and area per density as a result of the process. In the most preferred process, which moderately naps the surface, the average fibers are lifted, and the matrix height increases by 161% (Figure 2, Table 1).

[0023] [Table 1]

[0024] In the most preferred process, which involves moderately raising the surface nap, the cross-sectional area increases by 152% (Figure 2, Table 2). In all cases, the change in density is minimal.

[0025] [Table 2]

[0026] Quantitative analysis of preferred substrates showed that moderate napping increased matrix height, surface roughness, and volume by 642%, 672%, and 8999%, respectively (Table 3).

[0027] [Table 3]

[0028] When the matrix was coated without napping, insufficient material penetration and aggregation or clumping occurred, whereas napping showed improved coating of individual fibers and better penetration into the matrix. Cross-sectional SEM microscopy revealed that napping mitigated the problem of a "flat film" where the coating solidified on the surface, hindering the benefits of the porous structure and increasing rigidity (Figure 3).

[0029] Furthermore, more cracks were observed in the non-napped coating. Image analysis confirmed that the non-napped group had a small number of pores and voids on the surface, occupying only 12% of the total surface area, compared to 27% of the napped group.

[0030] The reduction in coating and aggregation of individual fibers in the napped substrate indicated improved pore volume and voids (15%), which is beneficial for blood penetration and also indicated enhanced binding of coated fibers to tissue. To further support these matrix properties, micro-CT imaging was performed to understand the coating on the napped surface. This visualization reaffirmed not only how napping improved matrix loft but also improved coating penetration and increased surface porosity. Cross-sectional analysis showed that napping disrupted the uniform film-like coating seen in the non-napped state, allowing for effective dispersion of the crosslinking agent without blocking the microporous structure of the matrix substrate (Figure 4). Finally, the improvement in porosity and the decrease in stiffness were 13.8% and 50%, respectively (Table 4).

[0031] [Table 4]

[0032] Functional evaluation was performed using tissue detachment tests and an ex vivo hemorrhage model of heparinized spleen. In qualified detachment tests, a patch was applied to calf skin tissue, compressed in Tris-buffered saline, and then detached, with the force measured at 90°.

[0033] To evaluate the ex vivo efficacy of hemostasis, nonwoven fabrics with napped coating, non-naked coating, and no napped coating were assessed for reduction in bleeding. Briefly, each patch was cut into a 1-inch x 1-inch square and placed on a 10 mm circular biopsy defect in an ex vivo spleen model (perfused with heparinized bovine blood) using tamponade for 2 minutes. Quantitative analysis confirmed that using the coated napped meltblown patch minimized or completely prevented bleeding in the ex vivo model.

[0034] These data confirmed that the hemostatic patches were fully functional and effective, in addition to improving tissue adhesion. Different degrees of nap affected the effectiveness of the hemostatic agent. All patches sealed to reduce and eventually stop bleeding, but as mentioned above, mild or severe nap was less effective compared to moderate nap.

[0035] In one embodiment, a highly adhesive hemostatic patch, comprising a combination of a crosslinkable coating and a napped meltblown matrix substrate, can be manufactured from a meltblown microfiber web using an absorbent and biocompatible polyester material such as Monocryl®, at a drum speed within the test range of 0.17 m / s, preferably 0.09 to 0.34 m / s, and at a distance from the collector within 25 inches, preferably 12 to 25 inches. Four layers can be constructed directly on the collector drum, but the preferred range is 2 to 10 layers. When using IV equal to 1.6 Monocryl®, the density of a four-layer structure is approximately 13 mg / cm³. 2These material properties and densities are necessary before napping.

[0036] A desirable degree of napping is achieved by a polishing technique, which loosens the entanglement of fibers and increases the height of the surface fibers and the entire matrix by about 161%, preferably in the range of 55-253%, and then increases the cross-sectional area by about 152%, preferably in the range of 57-434%. The resulting substrate can have its surface roughness and volume increased by about 676% and 8999%, respectively.

[0037] Methods for napping include both manual and automatic tools. Manual napping can be achieved with wire brushes, steel file cards, glass, or similar tools / materials that have a rough edge that can be used to cause abrasion, but are not limited to these. To achieve a preferred degree of napping, a steel file card (3.75 inches) is used to brush the surface of the nonwoven fabric several times in one direction until the fibers begin to peel from the surface (in this method, 5 to 15 strokes is a preferred working range, with 5 strokes resulting in "light" napping and 15 strokes in "heavy" napping). Alternatively, automatic napping methods include, but are not limited to, benchtop drill presses used with crimped wire wheels (e.g., 0.25-inch stem, 3-inch diameter) or other brush-based attachments. Other power tools and attachments such as wire brushes and abrasive flap wheels can also be used to achieve varying degrees of napping.

[0038] To achieve a high degree of napping without destructive abrasion, the matrix can be exposed to heat before brushing to soften the fibers. The degree of heating may vary depending on the polymer; in the case of Monocryl®, the structure is heated to 50°C for 15 minutes before napping.

[0039] To develop a fully functional hemostatic agent, crosslinkable active substances such as polyethylene glycol active esters (e.g., PEG-succinimidyl glutarate) are preferably coated sequentially, with or without the use of buffers and additives. To put this idea into practice, a 2-inch x 4-inch melt-blown matrix after fluffing is coated with a thin layer of buffer deeply embedded in a porous substrate either by ultrasonic spray coating (solubilization method) or dip coating (insoluble method). Examples include 1.25 mg / cm 2 sodium borate, or 2 mg / cm 2 bis-tris or 1 mg / cm 2 sodium bicarbonate. Next, 15 mg / cm 2 of 4-arm-PEG-amine-HCl (MW: 10 Kda) is ultrasonically coated, followed by coating with 18 mg / cm 2 of 4-arm-PEG-SG (MW: 10 Kda). The fluffed structure enables unique deposition of the crosslinkable active substance, resulting in enhanced tissue adhesion.

[0040] Exemplary plasma-derived (or related) hemostatic agents include proteins and peptides, and thus are not limited to natural ones and may be in recombinant or synthetic form, including prothrombin, thrombin, fibrin, fibronectin, factor X / Xa, factor VII / VIIa, factor IX / IXa, factor XI / XIa, factor XII / XIIa, tissue factor, von Willebrand factor, elastin, albumin, platelet surface glycoproteins, vasopressin and vasopressin group of analogs, epinephrine, selectin, plasminogen activator inhibitor, platelet activator, synthetic peptides, and any combination thereof having hemostatic activity.

[0041] The carrier sublayer may be in the form of a nonwoven material. An exemplary structural material is a synthetic polymer. The substrate may consist of components selected from aliphatic polyester polymers and / or copolymers of one or more monomers selected from the group consisting of D-lactic acid, L-lactic acid, lactide (including L-, D-, and meso forms), glycolic acid, glycolide, caprolactone, p-dioxanone, and trimethylene carbonate, and mixtures or blends thereof.

[0042] The base material may, alternatively or additionally, consist of layers of fabric of aliphatic polyester polymers, copolymers, or blends thereof. Aliphatic polyesters are typically synthesized by ring-opening polymerization of monomers including, but not limited to, lactide (including L- and D- and meso forms), glycolic acid, glycolide, caprolactone, p-dioxanone (1,4-dioxan-2-one), and trimethylene carbonate (1,3-dioxan-2-one). Aliphatic polyesters can, in some cases, be produced by polycondensation of D-lactic acid, L-lactic acid, and / or glycolic acid. In one embodiment, the fabric contains a copolymer of glycolide and lactide, in which the amount is about 70-95% on a molar basis of glycolide, with the remainder being lactide.

[0043] The porous substrate of the coating material has openings or pores over at least a portion of its surface. Suitable materials for forming the porous substrate include, but are not limited to, fibrous structures, as will be described in more detail below. In embodiments, the pores may be in a number and size sufficient to interconnect over the entire thickness of the porous substrate.

[0044] One or more sublayers of the porous substrate may be at least 0.1 cm thick, and in certain embodiments, about 0.2 to about 1.5 cm thick. The size of the pores in the sublayers of the porous substrate may be about 2 micrometers to about 300 micrometers, and in embodiments, about 50 micrometers to about 150 micrometers. It is assumed that the pores of the sublayers of the substrate may be arranged in any manner within the substrate. For example, the pores may be configured randomly or uniformly. In some embodiments, calcium alginate or copper alginate may be used to form the pores to form a honeycomb-shaped porous substrate. In yet another embodiment, the pores may be configured to create a gradient in the porous substrate. The gradient can further enhance the porous substrate's ability to absorb physiological fluids and move physiological fluids carrying a first co-reactive component toward a second co-reactive component.

[0045] In one embodiment, the substrate has a first co-reactive component coated on a first sublayer and a second co-reactive component coated on the first sublayer. The terms “first co-reactive component” and “second co-reactive component” mean a polymer, functional polymer, macromolecule, small molecule, or crosslinking agent that can participate in the reaction to form a network of crosslinked molecules such as a hydrogel.

[0046] In one embodiment, each of the first and second co-reactive components is polyfunctional, meaning that it contains two or more electrophilic or nucleophilic functional groups, for example, so that a nucleophilic functional group on the first co-reactive component can react with an electrophilic functional group on the second co-reactive component to form a covalent bond. At least one of the first or second co-reactive components contains three or more functional groups so that a precursor can bond to form a crosslinked polymer product as a result of an electrophilic-nucleophilic reaction. Such a reaction is called a "crosslinking reaction".

[0047] In certain embodiments, each of the first and second co-reactive components contains only one category of functional groups, i.e., either only nucleophilic groups or only electrophilic functional groups, insofar as both nucleophilic and electrophilic precursors are used in the crosslinking reaction. Therefore, for example, if the first co-reactive component has a nucleophilic functional group such as an amine, the second co-reactive component may have an electrophilic functional group such as N-hydroxysuccinimide. On the other hand, if the first co-reactive component has an electrophilic functional group such as sulfosuccinimide, the second co-reactive component may have a nucleophilic functional group such as an amine or thiol. Therefore, functional polymers such as proteins, poly(allylamine), styrene sulfonic acid, or amine-terminated bifunctional or polyfunctional poly(ethylene glycol) ("PEG") can be used.

[0048] The first and second co-reactive components may have a biologically inert and water-soluble core. When the core is in the water-soluble polymer region, preferred polymers that can be used include polyethers, polyalkylene oxides such as polyethylene glycol ("PEG"), polyethylene oxide ("PEO"), polyethylene oxide-co-polypropylene oxide ("PPO"), co-polyethylene oxide blocks or random copolymers, and polyvinyl alcohol ("PVA"); poly(vinylpyrrolidinone) ("PVP"); poly(amino acids); poly(saccharides) such as dextran, chitosan, alginates, carboxymethylcellulose, oxidized cellulose, hydroxyethylcellulose, hydroxymethylcellulose, and hyaluronic acid; and proteins such as albumin, collagen, casein, and gelatin. Polyethers, especially poly(oxyalkylene) or poly(ethylene glycol) or polyethylene glycol, are particularly useful. When the core is essentially a small molecule, the first and second co-reactive components can be made water-soluble by using any of a variety of hydrophilic functional groups. For example, the precursor can be made water-soluble by using water-soluble functional groups such as hydroxyl, amine, sulfonic acid, and carboxylic acid. Furthermore, subaric acid (subaric Although the N-hydroxysuccinimide ("NHS") ester of suberic acid is insoluble in water, adding a sulfonic acid group to the succinimide ring makes the NHS ester of suberic acid water-soluble without affecting its reactivity to amine groups.

[0049] In certain embodiments, both the first and second co-reactive components may be large, crosslinkable molecules. For example, in one embodiment, one of the precursors may be a polyfunctional PEG with a molecular weight of about 2,000 to about 20,000 daltons. In embodiments having electrophilic groups, this polyfunctional PEG can react with collagen having a molecular weight of about 100,000 daltons. In other embodiments, gelatin having a molecular weight of about 50,000 to about 100,000 daltons can be used instead of collagen.

[0050] In alternative embodiments, the co-reactive components and buffer are provided on the patch. An exemplary sealing patch / pad is PEG-NH2 * It contains HCl and PEG-NHS, a buffering salt, preferably an alkali buffering agent (borax) deposited on an absorbent substrate.

[0051] If it is desirable that the biocompatible crosslinked polymer resulting from the reaction of the first and second co-reactive components be biodegradable or absorbable, one or more of the first and second co-reactive components may have biodegradable bonds between their functional groups. The biodegradable bonds may optionally function as water-soluble cores of one or more precursors. Alternatively, the functional groups of the first and second co-reactive components can be selected such that the products of their reaction result in a biodegradable bond. For each approach, the biodegradable bond can be selected such that the resulting biodegradable biocompatible crosslinked polymer degrades, dissolves, or is absorbed within a desired timeframe. Preferably, a biodegradable bond that degrades to non-toxic products under physiological conditions is selected.

[0052] Biodegradable bonds may be chelates, or chemically or enzymatically hydrolyzable or absorbable. Exemplary chemically hydrolyzable biodegradable bonds include polymers, copolymers, and oligomers of glycosides, d-lactides, lactides, caprolactones, dioxanones, and trimethylene carbonates. Exemplary enzymatically hydrolyzable biodegradable bonds include peptide bonds that can be cleaved by metalloproteinases and collagenases. Further exemplary biodegradable bonds include polymers and copolymers of poly(hydroxy acids), poly(orthocarbonates), poly(anhydrides), poly(lactones), poly(amino acids), poly(carbonates), poly(saccharides), and poly(phosphonates). In embodiments, biodegradable bonds may include ester bonds. Some non-limiting examples include esters of succinic acid, glutaric acid, propionic acid, adipic acid, or amino acids, as well as carboxymethyl esters.

[0053] In some embodiments, a polyfunctional electrophilic polymer, such as multi-armed PEG functionalized with multiple NHS groups, can be used as a first co-reactive component, and a polyfunctional nucleophilic component, such as trilysine, can be used as a second co-reactive component. In other embodiments, a polyfunctional electrophilic polymer, such as multi-armed PEG functionalized with multiple NHS groups, can be used as a first co-reactive component, and a polyfunctional nucleophilic polymer, such as collagen and / or collagen derivatives, can be used as a second co-reactive component. The multi-armed PEG functionalized with multiple NHS groups may have, for example, four, six, or eight arms, and may have a molecular weight of about 5,000 to about 25,000. Many other examples of preferred first and second precursors are described in U.S. Patents 6,152,943; 6,165,201; 6,179,862; 6,514,534; 6,566,406; 6,605,294; 6,673,093; 6,703,047; 6,818,018; 7,009,034; and 7,347,850, the entire contents of each of these are incorporated herein by reference.

[0054] In the patch embodiment, the co-reactive components can be deposited on the matrix as individual layers, or as a mixture. The order of the layers may vary, but a preferred sealing patch or pad is formed together with the matrix using PEG-NH2 * It comprises HCl (or any other hydrogen halide), PEG-NHS, and a buffer salt (such as sodium tetraborate, MES, TRIS, bis-Tris, sodium bicarbonate), followed by a layer of buffer salt, a layer of protected PEG-amine, and a layer of PEG-NHS. Furthermore, although the number of arms and molecular weight of the material may vary, from the viewpoint of efficacy and stability, 4-arm-10K-NH2 *HCl and 4-arm-10K-NHS are preferred variants. Embodiments were evaluated with different coating sequences. Performance and stability are significantly affected by the position of the buffer deposited on the matrix using the spray coating process. Performance and stability were optimal when the buffer was deposited beneath both PEGs (i.e., furthest from the tissue when the matrix was applied).

[0055] The first co-reactive component may be applied to the porous substrate by any suitable method well known to those skilled in the art, including but not limited to spraying, brushing, dipping, injection, and lamination. In embodiments, the first co-reactive component may be applied as a coating on the substrate at any concentration, size, and configuration that can form a hemostatic coating. In embodiments, the first co-reactive component coating can penetrate into the pores of the porous substrate. In embodiments, the first co-reactive component may be applied to the porous substrate as a film laminated on at least one side of the substrate.

[0056] Similarly, the second co-reactive component may be applied to the porous substrate using any suitable method well known to those skilled in the art, including but not limited to spraying, brushing, dipping, injection, and lamination. In yet another embodiment, the second co-reactive component may be applied to the porous substrate in solution, followed by evaporation or freeze-drying of the solvent. In the embodiment, the second co-reactive component may be applied to the porous substrate as a coating on at least one side of the substrate, or as a laminated film on at least one side of the substrate.

[0057] When in use, the patch dressing is oriented so that the co-reactive components are applied directly to the tissue. In some embodiments, the first and second parts may be distinguishable from each other by adding contrast agents, surface textures, coloring, or other visual indicators. When in contact with tissue, such as injured tissue, the dressing absorbs physiological fluids, and the first co-reactive hydrogel component is dissolved by the fluid. As the fluid is absorbed into and moves through the dressing, it carries the dissolved first co-reactive component to the second co-reactive component and buffer. Finally, the first and second co-reactive components react to form a biocompatible crosslinked material, thereby assisting in the stabilization of the blood clot, tissue proliferation, and reconstruction as the scaffold decomposes. In some embodiments, the biocompatible crosslinked material produced by the reaction of the first and second co-reactive components also provides the dressing with anti-adhesion properties.

[0058] The following examples are provided for illustrative purposes only and are not intended to limit the scope of this disclosure.

[0059] Examples of matrix and napping processes: Using absorbent and biocompatible polyester materials such as Monocryl®, the meltblown microfiber web is extruded onto the drum at a preferred drum speed of 0.17 m / s and a distance of 25 inches from the drum to the die. When using IV equal to 1.6 Monocryl®, four layers are built directly onto the collector drum in this configuration, with a density of approximately 13 mg / cm³. 2 These material properties and densities are necessary before napping.

[0060] After cutting the meltblown matrix into 2-inch x 4-inch pieces, gently heat the nonwoven patch to 50°C for 15 minutes to soften the fibers, then use a 4-inch steel file card to brush the surface in one direction to create a napped surface until the overall height of the matrix increases by approximately 150%.

[0061] Example of a coating process: A 2-inch x 4-inch meltblown napped matrix is ​​coated with a thin layer of buffer deeply embedded in the porous substrate by either ultrasonic spray coating (solubilization method) or immersion coating (insolubilization method). An example is 1.25 mg / cm³. 2 Sodium borate, 2 mg / cm³ 2 Bis-tris or 1 mg / cm³ 2 Sodium bicarbonate is one example. Next, 15 mg / cm³ 2 The 4-arm PEG-amine-HCl (MW: 10 kDa) was ultrasonically coated, followed by 18 mg / cm³. 2 The 4-arm PEG-SG (MW: 10Kda) is ultrasonically coated.

[0062] The napped structure allows for unique deposition of cross-linking active substances deep within the matrix, ultimately resulting in a highly effective hemostatic agent with enhanced adhesion.

[0063] [Implementation Method] (1) A wound dressing comprising a meltblown substrate having at least two opposing main surfaces, and a coating layer applied to at least one of the opposing main surfaces, selected from the group consisting of a co-reactive hydrogel forming material, one or more plasma-based hemostatic agents, and combinations thereof, wherein the coated opposing main surface is napped. (2) The wound dressing according to Embodiment 1, wherein the wound dressing has an original thickness in the range of approximately 0.30 to 1.5 mm before fluffing, and the matrix height is increased in the range of approximately 50 to 250% relative to the original thickness. (3) The wound dressing according to Embodiment 1, wherein the wound dressing has an original thickness in the range of approximately 0.6 to 0.95 mm before fluffing, and the matrix height is increased in the range of approximately 55 to 175% relative to the original thickness. (4) The wound dressing according to Embodiment 1, wherein the wound dressing has an original thickness in the range of approximately 0.85 to 0.90 mm before fluffing, and the matrix height is increased by approximately 125 to 165% of the original thickness. (5) About 140~250mg / cm3 A wound dressing according to Embodiment 1, having a density in the range of [value].

[0064] (6) About 140~200mg / cm 3 A wound dressing according to Embodiment 2, having the density of [a certain value]. (7) About 140~150mg / cm 3 A wound dressing according to Embodiment 3, having a density of . (8) The wound dressing according to Embodiment 1, wherein the wound dressing has pores, and when measured by micro-CT analysis, the majority of the pores are in the range of 0.1 to 0.3 mm. (9) The wound dressing according to Embodiment 1, having a total open porosity of approximately 85% as measured by micro-CT analysis. (10) The wound dressing according to Embodiment 1, wherein the meltblown substrate is a bioabsorbable polymer material selected from the group consisting of polyglycolic acid (PGA), poly(lactic acid-co-glycolic acid) (PLGA), polylactic acid (PLA), polydioxanone (PDS), caprolactone / glycolide polyester, poly(caprolactone-co-glycolide), and combinations thereof.

[0065] (11) The wound dressing according to Embodiment 1, wherein the meltblown substrate is a copolymer of glycolide and epsilon-caprolactone. (12) The wound dressing according to Embodiment 1, wherein the hydrogel-forming material is at least two different polyfunctional polymers or polymer precursors each containing two or more electrophilic or nucleophilic functional groups. (13) The wound dressing according to Embodiment 1, wherein at least one of the hydrogel-forming materials has two or more nucleophilic functional groups that react with electrophilic functional groups on the second hydrogel-forming material to form a covalent bond. (14) The wound dressing according to Embodiment 1, wherein the hemostatic agent is selected from prothrombin, thrombin, fibrin, fibronectin, factor X / Xa, factor VII / VIIa, factor IX / IXa, factor XI / XIa, factor XII / XIIa, tissue factor, von Willebrand factor, elastin, albumin, platelet surface glycoprotein, vasopressin group consisting of vasopressin and its analogues, epinephrine, selectin, plasminogen activator inhibitor, platelet activator, synthetic peptide, and any combination thereof, which have hemostatic activity. (15) A method for manufacturing a wound dressing according to Embodiment 1, comprising melt-blowing microfibers as a web-like sheet, laminating the melt-blown sheets, bonding the layers of the melt-blown sheets, and coating the exposed main surface of the bonded layers of the melt-blown sheets by raising the nap.

[0066] (16) A method for sealing a tissue surface, comprising applying the wound dressing described in Embodiment 1 to the surface of damaged tissue.

Claims

1. A wound dressing comprising a meltblown substrate having at least two opposing main surfaces, and a coating layer applied to at least one of the opposing main surfaces and formed by crosslinking a first co-reactive component and a second co-reactive component, wherein the coated opposing main surface is napped, the first co-reactive component is poly(ethylene glycol) functionalized with a plurality of amine groups, and the second co-reactive component is poly(ethylene glycol) functionalized with N-hydroxysuccinimide groups.

2. Approximately 140-250mg / cm ３ A wound dressing according to claim 1, having a density in the range of [value].

3. The wound dressing according to claim 1, wherein the dressing has pores, and when measured by micro-CT analysis, the majority of the pores are in the range of 0.1 to 0.3 mm.

4. The wound dressing according to claim 1, having a total open porosity of approximately 85% as measured by micro-CT analysis.

5. The wound dressing according to claim 1, wherein the meltblown substrate is a bioabsorbable polymer material selected from the group consisting of polyglycolic acid (PGA), poly(lactic acid-co-glycolic acid) (PLGA), polylactic acid (PLA), polydioxanone (PDS), caprolactone / glycolide polyester, poly(caprolactone-co-glycolide), and combinations thereof.

6. The wound dressing according to claim 1, wherein the meltblown substrate is a copolymer of glycolide and epsilon-caprolactone.

7. The wound dressing according to claim 1, wherein the poly(ethylene glycol) in the first co-reactive component is in the form of a multi-arm, and the poly(ethylene glycol) in the second co-reactive component is in the form of a multi-arm.

8. The wound dressing according to claim 7, wherein the first co-reactive component is 4-arm-PEG-amine-HCl and the second co-reactive component is 4-arm-PEG-SG.

9. A method for manufacturing a wound dressing according to claim 1, comprising: melt-blowing microfibers as a web-like sheet; laminating the melt-blown web-like sheets; bonding the layers of the melt-blown web-like sheets; and coating the exposed main surface of the bonded layers of the melt-blown web-like sheets by raising the nap.

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