Visualizing hydrogel wound dressings and methods of making and using the same

Abstract

The application belongs to the technical field of biomedical engineering, and particularly relates to a visual hydrogel wound dressing, a preparation method and application thereof. The visual hydrogel wound dressing provided by the application is a hydrogel fiber membrane; the hydrogel fiber membrane comprises PUA fibers and antibacterial agent-containing nanovesicles dispersed in the PUA fibers; the component of the PUA fibers is a PUA polymer; the preparation raw material of the PUA polymer comprises aqueous polyurethane acrylate and alginate; the antibacterial agent-containing nanovesicles comprise nanovesicles and antibacterial agents loaded in the nanovesicles; and the nanovesicles are formed by PVP-PLA-PVP amphiphilic block copolymer. The wound dressing provided by the application can effectively promote wound healing through the synergistic effect of efficient antibiosis, drug sustained release and visual diagnosis.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biomedical engineering, and particularly relates to a visual hydrogel wound dressing and a preparation method and application thereof. BACKGROUND

[0002] At present, the main problem existing in skin wound management is bacterial infection. These infections not only delay wound healing, increase the burden of medical care in terms of cost and time, but also cause systemic infection or sepsis, which seriously threatens the life of patients. However, the current commonly used antibacterial dressing causes bacterial resistance due to the sudden release of antibacterial drugs, and the increased risk of infection caused by the need for frequent dressing changes; in addition, visual inspection can timely find out whether the wound condition appears red, turbid green liquid and / or swelling, which is conducive to the judgment of medical staff, however, the diagnosis process causes the wound to be exposed to the air, which is easy to cause bacterial infection.

[0003] Therefore, there is an urgent need for a wound dressing that can realize visual wound diagnosis and slow drug release. SUMMARY

[0004] The present application aims to provide a visual hydrogel wound dressing and a preparation method and application thereof. The wound dressing provided by the present application can effectively promote wound healing through the synergistic effect of efficient antibacterial, drug release and visual diagnosis.

[0005] The present application provides a visual hydrogel wound dressing, which is a hydrogel fiber membrane; the hydrogel fiber membrane comprises PUA fibers and antibacterial agent-containing nanovesicles dispersed in the PUA fibers; the component of the PUA fibers is a PUA polymer; the raw material for preparing the PUA polymer comprises waterborne polyurethane acrylate and alginate; the antibacterial agent-containing nanovesicles comprise nanovesicles and antibacterial agents loaded in the nanovesicles; the nanovesicles are formed by PVP-PLA-PVP amphiphilic block copolymer.

[0006] Preferably, the antibacterial agent is povidone iodine; the mass fraction of povidone iodine in the visual hydrogel wound dressing is 1.0-5.0%; the mass of the antibacterial agent-containing nanovesicles is 0.1-10.0% of the mass of the PUA fibers.

[0007] The present application also provides a preparation method of the visual hydrogel wound dressing described in the above technical solution, which comprises the following steps:

[0008] The waterborne polyurethane acrylate, alginate and photoinitiator are mixed for crosslinking reaction to obtain a PUA prepolymer solution;

[0009] Mixing the PVP-PLA-PVP amphiphilic block copolymer with deionized water to obtain the nano vesicle;

[0010] Mixing the nano vesicle with an antibacterial agent solution to perform a complexation reaction to obtain the nano vesicle containing the antibacterial agent;

[0011] Mixing the nano vesicle containing the antibacterial agent, a PUA prepolymer solution and a photoinitiator to obtain a spinning solution; performing electrospinning on the spinning solution to obtain a gel film layer;

[0012] Performing UV light irradiation on the gel film layer to obtain the visualized hydrogel wound dressing.

[0013] Preferably, the mass ratio of the aqueous polyurethane acrylate and the alginate is (2-4):1; the temperature of the crosslinking reaction is 60-90 DEG C, and the time is 0.5-1.0 h; the crosslinking reaction is performed under UV light irradiation.

[0014] Preferably, the preparation method of the PVP-PLA-PVP amphiphilic block copolymer comprises: mixing PVP, PLA, CuBr and an organic solvent to perform an atom transfer radical polymerization reaction to obtain the PVP-PLA-PVP amphiphilic block copolymer; the molar ratio of the PVP and the PLA is (30-60):1; the reaction temperature of the atom transfer radical polymerization reaction is 60-90 DEG C, and the reaction time is 3-5 h.

[0015] Preferably, the organic solvent in the atom transfer radical polymerization reaction is one or more of methyl ethyl ketone, acetone and N,N-dimethylformamide.

[0016] Preferably, after mixing the PVP-PLA-PVP amphiphilic block copolymer with deionized water, a mixed solution is obtained; filtering the mixed solution to obtain the nano vesicle; the filter membrane used in the filtering is a polycarbonate membrane.

[0017] Preferably, the voltage of the electrospinning is 17-20 kV, and the pump pushing speed is 0.005-0.015 mm / s.

[0018] Preferably, the time of the UV light irradiation is 1-2 h.

[0019] The application further provides the application of the visualized hydrogel wound dressing prepared by the preparation method in the preparation of a skin wound dressing.

[0020] Advantages:

[0021] The application provides a visual hydrogel wound dressing, which is a hydrogel fiber membrane; the hydrogel fiber membrane comprises PUA fibers and antibacterial agent-containing nanovesicles dispersed in the PUA fibers; the PUA fibers are composed of a PUA polymer; the raw material for preparing the PUA polymer comprises an aqueous polyurethane acrylate and an alginate; the antibacterial agent-containing nanovesicles comprise nanovesicles and antibacterial agents encapsulated in the nanovesicles; and the nanovesicles are formed by a PVP-PLA-PVP amphiphilic block copolymer. The hydrogel wound dressing provided by the application has a three-dimensional network and a porous structure, high transparency, and can realize visual diagnosis; the antibacterial agent is contained, and the hydrogel wound dressing has high antibacterial function; the porous structure can effectively lock water, so that the hydrogel wound dressing does not dissolve after swelling after absorbing water, regulates the release of the antibacterial agent, and realizes drug sustained release. In addition, the porous structure is in a physical adsorption / chemical bonding mode, which is beneficial to the storage of the nanovesicles, and the nanovesicles are in a film wrapping / embedding mode, which is beneficial to the encapsulation of the antibacterial agent, and the two modes synergistically regulate the sustained release of the antibacterial agent. In addition, the three-dimensional network structure endows the wound dressing with good mechanical properties. In summary, the hydrogel wound dressing provided by the application effectively promotes wound healing through the synergistic effect of efficient antibacterial function, drug sustained release and visual diagnosis.

[0022] Further, the hydrogel wound dressing provided by the application contains a low concentration of the antibacterial agent povidone iodine, which has low toxicity to cells and does not interfere with wound healing. BRIEF DESCRIPTION OF DRAWINGS

[0023] In order to more clearly illustrate the technical solutions in the embodiments of the application or the prior art, the following will briefly introduce the drawings needed in the embodiments.

[0024] Figure 1 It is a schematic diagram of the electrospinning principle of the application;

[0025] Figure 2 It is a schematic diagram of the use of the wound dressing prepared in Example 1 of the application, wherein (a) and (b) are diagrams of the adhesion of the wound dressing and gauze, and (c) is a diagram of the adhesion of the wound dressing and gauze on a human body;

[0026] Figure 3 It is a cross-sectional electron microscope image of the wound dressing prepared in Example 1 of the application, wherein the magnification of (a) is 5000, and the magnification of (b) is 2000;

[0027] Figure 4 It is a mechanical property diagram of the wound dressing prepared in Example 1 of the application;

[0028] Figure 5 It is an antibacterial test diagram of different samples, wherein (a) is a blank sample, (b) is Comparative Example 1, and (c) is Example 1. DETAILED DESCRIPTION

[0029] The application provides a visual hydrogel wound dressing, which is a hydrogel fiber film; the hydrogel fiber film comprises PUA fibers and antibacterial agent-containing nanovesicles dispersed in the PUA fibers; the PUA fibers are composed of a PUA polymer; the raw material for preparing the PUA polymer comprises aqueous polyurethane acrylate and alginate; the antibacterial agent-containing nanovesicles comprise nanovesicles and an antibacterial agent encapsulated in the nanovesicles; the nanovesicles are formed by a PVP-PLA-PVP amphiphilic block copolymer.

[0030] In the application, the antibacterial agent is preferably povidone iodine; the mass fraction of povidone iodine in the visual hydrogel wound dressing is preferably 1.0-5.0%, and specifically can be 3.0%; the mass of the antibacterial agent-containing nanovesicles is preferably 0.1-10.0% of the mass of the PUA fibers, and specifically can be 8.0%.

[0031] In the application, the visual hydrogel wound dressing is transparent, which can assist medical staff in visual diagnosis and detection.

[0032] The application further provides a preparation method of the visual hydrogel wound dressing.

[0033] The aqueous polyurethane acrylate, alginate and photoinitiator are mixed for crosslinking reaction to obtain a PUA prepolymer solution;

[0034] The PVP-PLA-PVP amphiphilic block copolymer is mixed with deionized water to obtain nanovesicles;

[0035] The nanovesicles are mixed with an antibacterial agent solution for complexation reaction to obtain antibacterial agent-containing nanovesicles;

[0036] The antibacterial agent-containing nanovesicles, the PUA prepolymer solution and the photoinitiator are mixed to obtain a spinning solution; the spinning solution is subjected to electrospinning to obtain a gel film layer;

[0037] The gel film layer is subjected to UV irradiation to obtain the visual hydrogel wound dressing.

[0038] The application mixes water-based polyurethane acrylate, alginate and photoinitiator to carry out cross-linking reaction, and obtains PUA prepolymer solution. In the application, the alginate is preferably sodium alginate; the mass ratio of the water-based polyurethane acrylate and the alginate is preferably (2-4):1, and specifically can be 5:2, 3:1 or 7:2; the temperature of the cross-linking reaction is preferably 60-90℃, and specifically can be 80℃; the time of the cross-linking reaction is preferably 0.5-1.0h, and specifically can be 1.0h; the cross-linking reaction is preferably carried out under UV light irradiation, the wavelength of the UV light is preferably 365nm, and the light intensity is preferably 4500μW / cm2; the cross-linking reaction is preferably carried out in deionized water; the cross-linking reaction is preferably carried out under stirring; the stirring is preferably magnetic stirring; the rotating speed of the magnetic stirring is preferably 200-400r / min, and specifically can be 250r / min, 300r / min or 350r / min; the photoinitiator in the cross-linking reaction is preferably one or both of TPO-L and BAPO; the mass of the photoinitiator is preferably 1.0-3.0% of the total mass of the water-based polyurethane acrylate and the alginate.

[0039] In the application, the reaction formula of the cross-linking reaction is as follows:

[0040]

[0041] The application mixes PVP-PLA-PVP amphiphilic block copolymer and deionized water to obtain nanovesicles. In the application, the preparation method of the PVP-PLA-PVP amphiphilic block copolymer preferably comprises: mixing PVP, PLA, CuBr and an organic solvent to carry out atom transfer radical polymerization reaction, and obtaining PVP-PLA-PVP amphiphilic block copolymer. In the application, the molar ratio of the PVP and the PLA is preferably (30-60):1, and specifically can be 40:1, 45:1 or 50:1; the reaction temperature of the atom transfer radical polymerization reaction is preferably 60-90℃, and specifically can be 80℃; the reaction time of the atom transfer radical polymerization reaction is preferably 3-5h, and specifically can be 3.5h, 4h or 4.5h; the organic solvent in the atom transfer radical polymerization reaction is preferably one or more of methyl ethyl ketone, acetone and N,N-dimethylformamide; the application does not have requirements on the amount of the organic solvent, as long as the reaction can be carried out.

[0042] In the application, the CuBr is an initiator of the atom transfer radical polymerization reaction; the mass content of the CuBr is preferably 0.4-1.0% of the total mass of the PVP and the PLA.

[0043] After obtaining the PVP-PLA-PVP amphiphilic block copolymer, the present application mixes the PVP-PLA-PVP amphiphilic block copolymer with deionized water to obtain a nanovesicle. In the present application, the PVP-PLA-PVP amphiphilic block copolymer undergoes a self-assembly reaction in deionized water to generate a nanovesicle.

[0044] In the present application, after mixing the PVP-PLA-PVP amphiphilic block copolymer with deionized water, a mixed solution is obtained, and the present application preferably filters the mixed solution to obtain a nanovesicle; the filter membrane used for the filtering is preferably a polycarbonate membrane; the mesh number of the polycarbonate membrane is preferably 200 mesh.

[0045] In the present application, the nanovesicle is in the form of a spherical micelle, specifically in the form of a dispersion liquid, and the filtrate obtained by filtering is a nanovesicle dispersion liquid.

[0046] After obtaining the nanovesicle, the present application mixes the nanovesicle with an antibacterial agent solution to perform a complexation reaction, thereby obtaining an antibacterial agent-containing nanovesicle (in the form of a dispersion liquid); the antibacterial agent solution is preferably a povidone iodine solution; the mass concentration of povidone iodine in the povidone iodine solution is preferably ≤5%, more preferably 1.0-5.0%; the nanovesicle is used in the form of a nanovesicle dispersion liquid, and the volume ratio of the nanovesicle dispersion liquid to the antibacterial agent solution is preferably 1:1-10:1; the complexation reaction is preferably performed for 0.5-1.0 h, and the complexation reaction can be performed at room temperature.

[0047] After obtaining the antibacterial agent-containing nanovesicle, the present application mixes the antibacterial agent-containing nanovesicle, a PUA prepolymer solution, and a photoinitiator to obtain a spinning solution. In the present application, the photoinitiator in the spinning solution is preferably one or both of TPO-L and BAPO; the mass content of the photoinitiator is preferably 0.1-3.0% based on 100% of the mass of the spinning solution; the antibacterial agent-containing nanovesicle is used in the form of a dispersion liquid, and the mass ratio of the antibacterial agent-containing nanovesicle dispersion liquid to the PUA prepolymer solution is preferably 1:1-10, specifically 1:2.

[0048] After obtaining the spinning solution, the present application performs electrospinning on the spinning solution to obtain a gel film layer. In the present application, the voltage of the electrospinning is preferably 17-20 kV, specifically 18 kV or 19 kV, and the pump pushing speed is preferably 0.005-0.015 mm / s, specifically 0.007 mm / s, 0.01 mm / s, or 0.012 mm / s.

[0049] After obtaining the gel film layer, the gel film layer is irradiated by UV light to obtain the visual hydrogel wound dressing; the time of the UV light irradiation is preferably 1-2h, and can be 1h or 1.5h in particular; the wavelength of the UV light is preferably 365nm, and the light intensity is preferably 4500μW / cm 2 .

[0050] The application further provides application of the visual hydrogel wound dressing in the technical solution or the visual hydrogel wound dressing prepared by the preparation method in the technical solution in preparation of skin wound dressings.

[0051] Figure 1 It is a schematic diagram of electrospinning principle of the application; the fibers in the hydrogel fiber film formed by electrospinning are uniform in diameter, and the nanovesicles containing the antibacterial agent are stably and uniformly dispersed in the fibers, which is beneficial to the sustained release of the drug.

[0052] In order to further illustrate the application, the visual wound dressing, the preparation method and the application thereof provided by the application are described in detail below in combination with the drawings and examples, but they should not be understood as limiting the protection scope of the application.

[0053] Example 1

[0054] (1) Preparation of the hydrogel: 3.0g of waterborne polyurethane acrylate (PUA) and 1.0g of sodium alginate are added to deionized water 20mL, and the mixture is magnetically stirred at 80℃ and a rotation speed of 300r / min for 0.5h, 0.04g of a photoinitiator TPO-L is added, and the mixture is irradiated by UV light for 1h (wavelength: 365nm, light intensity: 4500μW / cm 2 ), to obtain a PUA prepolymer solution;

[0055] (2) Preparation of the nanovesicles containing the antibacterial agent: 4.0g of hydrophilic PVP and 0.1g of hydrophobic PLA are added to methyl ethyl ketone 30mL, 0.02g of CuBr is added as an initiator, and an atom transfer radical polymerization reaction is performed at 80℃ for 4h to prepare a PVP-PLA-PVP amphiphilic block copolymer;

[0056] The prepared PVP-PLA-PVP amphiphilic block copolymer is poured into deionized water 100mL, filtered through a 200-mesh polycarbonate membrane, and a nanovesicle (spherical micelle) dispersion liquid is obtained;

[0057] The prepared nanovesicle dispersion liquid is added to a povidone iodine solution 10mL with an antibacterial agent concentration of 1.5wt%, PVP is complexed with iodine, the complexing temperature is room temperature, and the time is 0.5h, and the nanovesicles containing the antibacterial agent are prepared;

[0058] (3) Preparation of the wound dressing: 12 g of the nano-vesicles (dispersion) containing the antibacterial agent was added to 24 g of the PUA prepolymer solution, and 0.04 g of the photoinitiator was added thereto to obtain an electrospinning solution;

[0059] The obtained electrospinning solution was spun under the conditions of a voltage of 17 kV and a pump pushing speed of 0.01 mm / s, and after UV light irradiation (wavelength of 365 nm and light intensity of 4500 μW / cm 2 ) for 1 h, the wound dressing was prepared.

[0060] Figure 2 Figure 1 is a schematic diagram of the wound dressing prepared in Example 1 of the present application, wherein (a) and (b) are diagrams of the adhesion of the wound dressing to gauze, and (c) is a diagram of the adhesion of the wound dressing to gauze on a human body; it can be seen from the figure that the wound dressing prepared in the present application is transparent and can be used for visual diagnosis on a human wound. Figure 2

[0061] Example 2

[0062] The difference from Example 1 is that in step (2), 4.5 g of the hydrophilic PVP and 0.1 g of the hydrophobic PLA were added to the methyl ethyl ketone.

[0063] Example 3

[0064] The difference from Example 1 is that in step (2), 5.0 g of the hydrophilic PVP and 0.1 g of the hydrophobic PLA were added to the methyl ethyl ketone.

[0065] Comparative Example 1

[0066] 3.0 g of the aqueous polyurethane acrylate (PUA) and 1.0 g of the alginate were added to deionized water, and under magnetic stirring at 80℃ for 0.5 h, 0.04 g of the photoinitiator TPO-L was added, and UV light irradiation was performed for 1 h to obtain a PUA prepolymer solution; the obtained PUA prepolymer solution was electrospun, and the electrospun film was subjected to 0.5 h of UV light irradiation (wavelength of 365 nm and light intensity of 4500 μW / cm 2 ), to obtain a gel dressing.

[0067] Test Example

[0068] Figure 3 Figure 2 is a cross-sectional electron microscope image of the wound dressing prepared in Example 1 of the present application, wherein the magnification of (a) is 5000, and the magnification of (b) is 2000; it can be seen from the figure that the wound dressing prepared in the present application is transparent and can be used for visual diagnosis on a human wound. Figure 3 ​As can be seen from the figure, the wound dressing has a three-dimensional network structure and a porous structure, the three-dimensional network structure gives the wound dressing good mechanical properties, and the porous structure can effectively lock water, so that the wound dressing does not dissolve after swelling after absorbing water, and the release of the antibacterial drug is regulated.

[0069] Figure 4 The mechanical property figure of the wound dressing prepared in Example 1 of the present application is shown in Figure 2. Figure 4 As can be seen from the figure, the wound dressing prepared in the present application can still restore to the original state after being twisted and bent.

[0070] Antibacterial performance test:

[0071] Culture bacteria liquid

[0072] Day 1: Take the E. coli strain on the plate and continuously streak, streak three lines on the upper left oblique, then sterilize the inoculation ring by burning, then lightly streak at the end of the last line on the upper left oblique, then continuously streak three lines on the upper right oblique, then lightly streak at the end of the last line on the upper right oblique, and then continuously horizontally streak three lines below. Finally, place the plate in the incubator, the culture temperature is 37℃, and the culture time is 24h.

[0073] Day 2: Take a single colony with an inoculation ring and inoculate it in 20mL of broth, and place it in the incubator, the culture temperature is 37℃, and the culture time is 18h, and the shaking rate is 130r / min.

[0074] Day 3: Measure the concentration of the cultured bacteria liquid with a UV spectrophotometer, and use the next step when the concentration reaches 1~5×10 9 CFU / mL. Take 1mL of bacteria liquid and add 9mL of PBS to mix, then take 1mL of the solution and add 9mL of PBS to mix, so that the concentration is 1~5×10 7 CFU / mL. Sample preparation: cut the hydrogel wound dressing prepared in Example 1 to a size of 0.15g. Put 0.15g of the sample in a test tube containing 14mL of PBS, the blank sample does not contain any gel, and the sample of Comparative Example 1 is the PUA hydrogel prepared in Comparative Example 1, and each adds 1mL of bacteria liquid. Place in the incubator, the culture temperature is 24℃, and the culture time is 18h, and the shaking rate is 100r / min.

[0075] Day 4: Dilute the culture and drop the plate. Take 0.1mL of bacteria liquid and add 0.9mL of PBS to mix, then take 0.1mL of the solution and add 0.9mL of PBS to mix, repeat three times to form four concentration gradients of 10 times, 100 times, 1000 times and 10000 times and mark. Take an agar plate and divide it into four areas with a cross and mark, respectively. Take 0.025mL of the four dilution solutions and drop them into the four areas, about 10 drops or so, and titrate with a 0.0025mL range pipette, and pay attention to the droplets not to be connected.

[0076] Fifth day: observe the number of bacteria, judge the antibacterial performance.

[0077] Figure 5 The figure of antibacterial test of different samples, wherein, (a) is blank sample, (b) is comparative example 1, (c) is example 1; from Figure 5 It can be seen from that compared with the blank sample, the wound dressing prepared by the application has good antibacterial effect, while the wound dressing prepared by comparative example 1 still has a large number of bacteria breeding, and the antibacterial effect is poor.

[0078] In summary, the wound dressing prepared by the application not only has good mechanical properties, but also effectively promotes wound healing through the synergistic effect of efficient antibacterial, drug sustained release and visual diagnosis.

[0079] Although the above embodiment has made a detailed description of the application, it is only a part of the embodiment of the application, not all the embodiments, and people can also obtain other embodiments according to the embodiment without creativity, which all belong to the protection scope of the application.

Claims

1. A visualizing hydrogel wound dressing, characterized in that, The visual hydrogel wound dressing is a hydrogel fiber membrane; the hydrogel fiber membrane comprises PUA fibers and antibacterial agent-containing nanovesicles dispersed in the PUA fibers; the composition of the PUA fibers is a PUA polymer; the raw material for preparing the PUA polymer comprises aqueous polyurethane acrylate and alginate; the antibacterial agent-containing nanovesicles comprise nanovesicles and an antibacterial agent encapsulated in the nanovesicles; the nanovesicles are formed of a PVP-PLA-PVP amphiphilic block copolymer.

2. The visible hydrogel wound dressing of claim 1, wherein, The antibacterial agent is povidone iodine; the mass fraction of povidone iodine in the visual hydrogel wound dressing is 1.0-5.0%; the mass of the antibacterial agent-containing nanovesicles is 0.1-10.0% of the mass of the PUA fibers.

3. The method of producing a visualizing hydrogel wound dressing according to any one of claims 1 to 2, characterized in that, The method comprises the following steps: mixing aqueous polyurethane acrylate, alginate and a photoinitiator to perform a crosslinking reaction, to obtain a PUA prepolymer solution; mixing a PVP-PLA-PVP amphiphilic block copolymer with deionized water to obtain nanovesicles; mixing the nanovesicles with an antibacterial agent solution to perform a complexation reaction, to obtain antibacterial agent-containing nanovesicles; mixing the antibacterial agent-containing nanovesicles, the PUA prepolymer solution and the photoinitiator to obtain a spinning solution; performing electrospinning on the spinning solution to obtain a gel membrane layer; performing UV light irradiation on the gel membrane layer to obtain the visual hydrogel wound dressing.

4. The production method according to claim 3, characterized by, The mass ratio of the aqueous polyurethane acrylate and the alginate is (2-4):1; the temperature of the crosslinking reaction is 60-90℃, and the time is 0.5-1.0h; the crosslinking reaction is performed under UV light irradiation.

5. The preparation method according to claim 3, characterized in that, After mixing the PVP-PLA-PVP amphiphilic block copolymer with deionized water, a mixed solution is obtained; the mixed solution is filtered to obtain nanovesicles; the filter membrane used in the filtering is a polycarbonate membrane.

6. The preparation method according to claim 3, characterized in that, The voltage of the electrospinning is 17-20kV, and the pump pushing speed is 0.005-0.015mm / s.

7. The preparation method according to claim 3, characterized in that, The time of the UV light irradiation is 1-2h.

8. Use of the visual hydrogel wound dressing of any one of claims 1-2 or the visual hydrogel wound dressing prepared by the preparation method of any one of claims 3-7 in the preparation of a skin wound dressing.

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