Wound dressing with tissue fluid discharge and blood scab adhesion prevention functions and preparation method thereof
Technical Field
The invention relates to the field of new materials, in particular to a wound dressing with tissue fluid discharge and blood scab adhesion prevention functions and a preparation method thereof.
Background
The wound is the most common health problem in human life, a plurality of wound dressings with different types and different wound symptoms are widely researched and manufactured, and good effects are achieved, however, more dressings are still medical gauze dressings clinically used at present, and only a small amount of new dressing products can be widely applied to clinical treatment. In use, the medical gauze dressing has good ventilation capability, can absorb tissue fluid and blood of a wound, and has a certain effect of preventing wound infection. But in clinical use, the medical gauze dressing has slower hemostatic speed, does not have the capability of promoting healing and accelerating blood to wounds, is difficult to achieve better effect at a large-area wound part or a wound with large bleeding amount, and can be adhered to the wounds by the formed scab after blood is absorbed by the gauze to coagulate, so that secondary wounds are very easy to occur when the gauze is removed, the secondary bleeding affects wound repair, and the health of a patient is damaged again. Thus, a wound dressing is prepared that prevents adhesion to the wound and is critical to healing after repair of the wound in a patient.
In recent years, there have been some reports on the design of wound dressings from the surface interface point of view, for example, the use of super-hydrophilic graphene sponge to rapidly absorb moisture in blood, form a layer of dense blood cells and platelets, thereby promoting blood coagulation, or the use of β -chitosan coating to enhance blood wettability to promote blood coagulation, etc. Meanwhile, some researchers use hydrophobic wound dressing to play a certain role in preventing adhesion. However, super-hydrophobic wound dressings have the unique advantage of preventing wound adhesion and creating secondary wounds. This is mainly the case when blood exists in a Cassie state on a superhydrophobic surface, fibrin first adsorbs on the superhydrophobic surface and promotes blood coagulation. After the wound is coagulated, an air layer formed by a Cassie state exists on the surfaces of the scab and the wound dressing, so that the scab is prevented from being in direct contact with the wound dressing, and the side effect of secondary bleeding is reduced. The super-hydrophobic wound dressing has the unique effects of promoting the rapid growth of fibrin, realizing rapid coagulation, no blood loss, antibacterial property and thrombus self-separation, has the unique advantages of preparing the super-hydrophobic wound dressing by using Carbon Nanofiber (CNF) doped in Polydimethylsiloxane (PDMS) and Polytetrafluoroethylene (PTFE), and verifies that the wound dressing has a super-hydrophobic surface. However, the super-hydrophobic wound dressing still has some common problems that 1) the common super-hydrophobic wound dressing is poor in stability, cannot drain blood for a long time, is easy to produce secondary wounds after being adhered to the wound after contacting the surface for a certain time, 2) most of the super-hydrophobic medical devices are prepared by using fluorine-containing materials, the fluorine-containing materials and the blood are contacted for a long time, especially fluorine-containing small molecules fall off, and can generate strong toxicity and immune response to organisms, and 3) excessive liquid cannot be discharged when exuding to wound bleeding, suppuration, tissue fluid and the like, so that the coagulation and healing of the wound are affected.
Aiming at the problems, a hydrophilic array with smaller size is introduced into the surface of the super-hydrophobic wound dressing, so that excessive liquid at the wound can be discharged while the blood crust on the surface of the dressing is ensured to be easily removed. Superhydrophobic surfaces are typically obtained by low surface energy treatment. The super-hydrophobic surface is activated or perforated to obtain a hydrophilic array channel capable of enabling liquid to pass through, and then the back side of the super-hydrophobic dressing is subjected to super-hydrophilic modification to enhance the capillary force of the liquid when the liquid passes through the surface of the super-hydrophobic wound dressing.
Disclosure of Invention
In view of the problems that the existing wound dressing is easy to generate secondary wounds when stripped, the blood-repellent effect of the super-repellent wound dressing is unstable, more tissue fluid and blood exist at a wound site to influence wound healing and the like, the present disclosure provides a method for preparing the super-repellent wound dressing and establishing a hydrophilic array on the surface of the super-repellent wound dressing, and the dressing has the capability of draining excessive liquid from the wound while maintaining the super-hydrophobicity of the dressing, and blood crust is easy to strip from the wound after the wound is coagulated, so that secondary wounds at the wound are not caused, and the problems in one aspect or multiple aspects of the prior art are solved.
Aiming at the problems in the prior art, the application provides a wound dressing with tissue fluid discharge and blood crust adhesion prevention, which comprises super-hydrophobic particles, a solvent and a polymer raw material;
super-hydrophobic particles, a micro-nano structure is constructed on the surface of the fiber, and the surface energy is reduced;
the solvent provides environment for dilution, uniform dispersion and mixing of the super-hydrophobic particles and the polymer raw materials, is favorable for infiltration and coating of the mixed solution on the non-woven fabric to prepare the super-hydrophobic wound dressing, and is matched with the polarities of the super-hydrophobic particles and the polymer raw materials.
Preferably, the superhydrophobic particles are one or more of methyl SiO 2 particles, ethyl SiO 2 particles, PDMS modified SiO 2 particles, octadecyl SiO 2 particles, and perfluorooctadecyl SiO 2 particles.
Further, the size of the super-hydrophobic nano-particles is one or more of 10-20nm,200-300nm and 1-10 μm.
Preferably, the solvent is one or more selected from ethyl acetate, butyl acetate, acetone, ethanol, tetrahydrofuran, DMF, DMSO, methyl ethyl ketone, toluene, xylene.
Preferably, the polymer raw material is one or more selected from polyurethane, polyolefin, PDMS, PVDF, PTFE, PCL, PVA, PLA containing curing agent and epoxy resin.
Further, the dilution concentration of the super-hydrophobic particles dissolved in the solvent is 1mg/mL-100mg/mL.
Further, the ratio of the super-hydrophobic particles to the polymer raw material which are diluted and dissolved in the solvent is 50:1-1:50.
Further, the non-woven fabric material is dip-coated in the prepared mixed solution for 5-1000 seconds, or one or more of spray-coating for 5-1000 seconds by using a spray gun and spin-coating.
Further, the non-woven fabric material with the coating is put into an oven for curing and drying, the temperature is set to be 40-120 ℃, and the drying time is set to be 1-48 hours.
The application also relates to a preparation method of the wound dressing with the functions of discharging tissue fluid and preventing blood crust from sticking, which comprises the following steps:
S1, mixing super-hydrophobic particles, a solvent and polymer raw materials in proportion, and uniformly dispersing the mixture by using an ultrasonic cleaner for 10-60 minutes;
S2, cutting the non-woven fabric into proper size, and soaking the non-woven fabric in the mixed solution with complete ultrasonic dispersion for 5-1000 seconds to form the super-blood-repellent non-woven fabric;
S3, taking out the super-blood-repellent non-woven fabric, and drying and curing in a baking oven at 40-120 ℃ to volatilize the solvent completely for 1-48 hours.
The application also relates to a preparation method of the wound dressing with the functions of discharging tissue fluid and preventing blood crust from sticking, which comprises the following steps:
m1, uniformly mixing ethanol, ammonia water, distilled water and Tetraethoxysilane (TEOS), and standing at room temperature to form SiO 2 sol;
M2, soaking the original fiber cloth in SiO 2 sol, drying at room temperature, and curing in an oven;
M3, putting the sample into hexadecyl trimethoxy silane (HDTMS) diluted by ethanol;
And M4, finally curing in an oven to obtain the super-hydrophobic fiber cloth.
The application also relates to a preparation method of the wound dressing with the functions of tissue fluid discharge and blood scab adhesion prevention, which comprises the following steps of adding deionized water into Octadecyl Trichlorosilane (OTS), mixing, standing after ultrasonic treatment, adding n-hexane to terminate the assembly process, standing after uniform mixing, soaking the original fiber cloth in the re-shaking n-hexane dispersion liquid, and drying in a drying oven.
The application also relates to a preparation method of the wound dressing with the functions of tissue fluid discharge and blood scab adhesion prevention, which comprises the following steps of dissolving polyvinylidene fluoride (PVDF) in N, N-Dimethylformamide (DMF), preparing the super-hydrophobic SiO2 nano particles/PVDF into an electrostatic spinning solution, and preparing the super-hydrophobic fiber by using a handheld electrostatic spinning instrument to form the super-hydrophobic wound dressing.
Preferably, the preparation method of the wound dressing with the functions of tissue fluid discharge and blood scab adhesion prevention comprises the following steps:
A4, arranging a pair of needle points on one side of the super-blood-thinning wound dressing, and respectively connecting the positive electrode and the negative electrode of a direct current power supply;
A5, starting a direct current power supply, increasing voltage until the needle tip discharges, and starting counting when air breaks down;
a6, after the discharge breaks down air, hydrophilic points are manufactured on the super-blood-repellent wound dressing;
A4, the super-blood-thinning wound dressing and the needle point relatively move to prepare a hydrophilic dot array.
Preferably, the preparation method of the wound dressing with the functions of tissue fluid discharge and blood scab adhesion prevention comprises the following steps:
B4, manufacturing a stainless steel plate with a preset aperture and a preset distance by using laser drilling;
B5, pressing the super-hydrophobic wound dressing by using the prepared stainless steel plate, and fixing the stainless steel plate and the super-hydrophobic wound dressing;
B6, placing the fixed super-blood-repellent wound dressing in a plasma cleaner for activation to prepare a hydrophilic dot array.
Preferably, the preparation method of the wound dressing with the functions of tissue fluid discharge and blood scab adhesion prevention comprises the following steps:
And C1, horizontally placing the prepared super-blood-repellent wound dressing on a laser object stage.
C2, using Ezcad software to write the punching program.
And C3, starting a laser, and punching the super-blood-repellent wound dressing to prepare a hydrophilic dot array.
Further, in step S2, the aperture range of the laser drilling is 50-1000 μm, the pitch is 500-2000 μm, and the number of laser scans is 10-500.
Compared with the prior art, the wound dressing with the tissue fluid discharge and the blood scab adhesion prevention functions and the preparation method thereof have the following beneficial effects:
1. The method has simple process steps, can super-dredge various wound dressings and has wide application range;
2. the method can successfully increase the stability of the super-blood-repellent wound dressing and ensure the long-term stable blood-repellent of the dressing;
3. The wound dressing prepared by the method can effectively prevent the adhesion of the wound, and scabs are easy to peel off from the wound, so that secondary wounds at the wound are avoided;
4. the wound dressing prepared by the method can ensure that the dressing has the capacity of discharging excessive liquid from a wound while maintaining the super-hemophobic performance of the dressing, thereby being beneficial to the coagulation and healing of the wound;
5. the method disclosed by the invention is prepared by using a fluorine-free material, and has good biocompatibility.
Drawings
The invention will be described in more detail hereinafter on the basis of embodiments and with reference to the accompanying drawings. Wherein:
FIG. 1 shows a schematic representation of the use of a super-phobic wound dressing with a hydrophilic array of the invention;
FIG. 2 shows a picture of the super-phobic wound dressing of the invention under scanning electron microscopy;
FIG. 3 shows the results of water contact angle tests of the super-phobic wound dressing of the invention prepared according to different particle to polymer ratios;
FIG. 4 shows stability and blood thinning effects tests of super-blood thinning wound dressings prepared by different particle to polymer ratios of the present invention;
FIG. 5 shows a scab release force test of the super-phobic wound dressing of the invention;
FIG. 6 shows a photograph of a super-phobic wound dressing of the invention formed into a hydrophilic array by laser drilling and a photomicrograph;
FIG. 7 shows a performance test of the super-hydrophobic wound dressing with hydrophilic array of the present invention, through which blood is exported;
figure 8 shows a diagram of the invention in terms of the attachment of scabs to a dressing as seen in SEM cross-section.
Detailed Description
The invention will be further described with reference to the accompanying drawings.
As shown in FIG. 1, the present invention provides a method for simply preparing a super-hydrophobic wound dressing, comprising super-hydrophobic particles (component A), solvent (component B), and polymer raw material (component C).
Component A
The component A is super-hydrophobic particles, is a basic component for providing super-hemophobic performance, and can construct a micro-nano structure on the surface of the fiber and reduce the surface energy.
Component A may be selected from one or more of methyl SiO 2 particles, ethyl SiO 2 particles, PDMS (polydimethylsiloxane) modified SiO 2 particles, octadecyl SiO 2 particles, perfluorooctadecyl SiO 2 particles, the size of the superhydrophobic nanoparticles may be selected from one or more of 10-20nm,200-300nm,1-10 μm, preferably 10-20nm.
Component B
The component B is a solvent, provides environment for dilution, uniform dispersion and mixing of the component A and the component C, and is favorable for the mixed solution to infiltrate and coat on non-woven fabrics to prepare the super-oleophobic wound dressing.
Suitable component B may be selected based on the polarity of component A and component C. Generally speaking. The component B is one or more selected from ethyl acetate, butyl acetate, acetone, ethanol, tetrahydrofuran, DMF (N, N-dimethylformamide), DMSO (dimethyl sulfoxide), methyl ethyl ketone, toluene and xylene.
Component A is diluted and dispersed in component B in a dilution ratio of 1mg/mL-100mg/mL, preferably 5mg/mL-40mg/mL.
Component C
The component C is a polymer, and the polymer is one or more selected from polyurethane, polyolefin, PDMS (polydimethylsiloxane) containing a curing agent, PVDF (polyvinylidene fluoride), PTFE (polytetrafluoroethylene), PCL (polycaprolactone), PVA (polyvinyl alcohol), PLA (polylactic acid) and epoxy resin.
Method for preparing super-blood-dredging wound dressing
Firstly, the components are mixed according to the proportion, and the ultrasonic cleaner is used for uniformly dispersing the components for 10 to 60 minutes. The ultrasonic dispersion of the solution can lead the polymer and the particles to be uniformly dispersed in the solvent, and can lead the polymer and the particles to be uniformly bonded on the non-woven fabric during the dip-coating of the non-woven fabric, thus preparing the super-blood-repellent wound dressing.
The nonwoven fabric is cut to a proper size and soaked in the mixed solution of the ultrasonic dispersion completion for 5 to 1000 seconds, preferably 60 to 600 seconds.
Taking out the super-blood-repellent non-woven fabric, and drying and curing in a 40-120 ℃ oven, preferably 60-80 ℃ to volatilize the solvent completely, wherein the curing time is 1-48 hours, preferably 4-12 hours.
After the curing process is finished, the temperature of the oven is reduced to room temperature, the object is taken out, and the super-blood-repellent wound dressing is successfully prepared.
The preparation method of the super-blood-dredging wound dressing comprises the following steps:
A mixed solution was prepared by uniformly mixing 25mL of ethanol, 1mL of ammonia water (20% wt), 3.6mL of distilled water, and 11mL of Tetraethoxysilane (TEOS), and standing at room temperature for 2 hours to form a SiO 2 sol. After soaking the original fiber cloth in the SiO 2 sol for 5min, it was dried at room temperature for 24h and cured in a 160 ℃ oven for 5min. And then placing the sample into hexadecyl trimethoxy silane (HDTMS) diluted to 4% by ethanol for 4 hours, and finally curing the sample in a 120 ℃ oven for 1 hour to obtain the super-hydrophobic fiber cloth.
A preparation method of the super-blood-dredging wound dressing comprises the following steps:
mu.L of deionized water was added to 1mL of Octadecyl Trichlorosilane (OTS), mixed and sonicated for 30min, then allowed to stand for 90min, 10mL of n-hexane was added to terminate the assembly process, and after uniform mixing, allowed to stand overnight. And (3) soaking the original fiber cloth in the re-shaking normal hexane dispersion liquid for 10 seconds, and drying in a 60 ℃ oven to successfully prepare the super-hydrophobic fiber cloth.
A preparation method of the super-blood-dredging wound dressing is four:
polyvinylidene fluoride (PVDF) is dissolved in N, N-Dimethylformamide (DMF) according to the proportion of 5.0%,7.5%,10.0%,12.5% and 15.0% by weight, and then is prepared into an electrostatic spinning solution according to the proportion of 0.5%,1.0%,2.0%,3.0% and 5.0% by weight (super-hydrophobic SiO 2 nano particles/PVDF), and then super-hydrophobic fibers are prepared by using a handheld electrostatic spinning instrument, so that the super-hydrophobic wound dressing is formed.
Method for preparing super-blood-repellent wound dressing with hydrophilic array
The present disclosure also provides various methods of preparing hydrophilic arrays on superhydrophobic wound dressings, suitable for use with a variety of nonwoven fiber dressings.
Electric breakdown method:
The prepared super-blood-repellent wound dressing is horizontally placed on a platform, and the lower part of the platform and the upper end of the bracket are exposed with a needle point and are connected with the anode and the cathode of a direct current power supply. The needle point on the platform is contacted with the super-blood-thinning wound dressing, and the distance between the needle point at the upper end and the dressing is 1-10cm, preferably 3-7cm. And starting a direct current power supply, increasing the voltage until the needle tip discharges, wherein the voltage range of the direct current power supply is 8-15kv, and starting counting when air is broken down. The number of discharge breakdowns is 10 to 500, preferably 60 to 120. A hydrophilic point is formed on the super-blood-repellent wound dressing after the discharge breaks down the air. And translating the platform or the fiber cloth by a certain size to prepare the hydrophilic dot array.
Plasma activation method:
Stainless steel plates with different pore diameters and different distances are manufactured by laser drilling, wherein the pore diameter range of the laser drilling is 10-1000 mu m, the interval is 500-20000 mu m, the preferred pore diameter range is 200-500 mu m, and the interval is 10000-15000 mu m. The prepared super-hydrophobic wound dressing is pressed by the prepared stainless steel plate and fixed by a clip. The clamped super-phobic wound dressing is placed in a plasma cleaner for activation for 30-1000 seconds, and preferably for 60-180 seconds, so as to prepare a hydrophilic dot array.
Laser method:
And (5) placing the prepared super-blood-repellent wound dressing on a laser object stage. The puncturing program is written using Ezcad software from a computer. The laser perforation has a pore diameter ranging from 50 to 1000 μm, a pitch ranging from 500 to 2000 μm, a number of laser scans ranging from 10 to 500, preferably a pore diameter ranging from 200 to 500 μm, a pitch ranging from 1000 to 1500 μm, and a number of laser scans ranging from 100 to 300. Starting a laser to perform laser perforation on the super-blood-repellent wound dressing to prepare a hydrophilic dot array.
Embodiments of the present disclosure will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are merely illustrative of the present disclosure and should not be construed as limiting the scope of the present disclosure. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Example 1
The commercially available SiO 2 was hydrophobically modified, and due to the hydrophilic nature of SiO 2, reagents such as methyltrichlorosilane, octyltrichlorosilane, octadecyltrichlorosilane, polydimethylsiloxane were used, and the SiO 2 particles were diluted into the solvent at a ratio of reagent=10:1. The solvent is a reagent with similar polarity to the reagent, such as n-hexane, ethanol, ethyl acetate, toluene, etc. After stirring for 2-6 hours, volatilizing the solvent by using a vacuum drying oven at 60-80 ℃ to obtain the super-hydrophobic nano particles.
Example 2
20ML of the mixed solution (20 mg/mL of the super-hydrophobic nanoparticles, wt% of the super-hydrophobic nanoparticles: PDMS wt% = 5:1, wt% of PDMS curing agent wt% = 10:1, solvent ethyl acetate) was prepared. Ultrasonic cleaning is carried out for 20 minutes by using an ultrasonic cleaner, so that the polymer and the super-hydrophobic nano particles are uniformly mixed and dispersed.
Taking cut non-woven fabrics with the length of 5cm and the length of 5cm, soaking in the prepared mixed solution. After 5 minutes, the non-woven fabric is taken out, put into a 60 ℃ oven for drying and curing for 8 hours, after the curing is finished, the non-woven fabric is taken out and cooled to room temperature, pressed to be flat and subjected to subsequent testing.
As shown in fig. 2, the random positions of the samples were randomly selected, and it was observed by using a scanning electron microscope that the surface of the super-hydrophobic wound dressing had a remarkable rough structure formed of super-hydrophobic nanoparticles, while the surface of the non-woven fabric which was not dip-coated was smoother.
Example 3
The experimental procedure and operational procedure were the same as in example 1, but the ratio of wt% of superhydrophobic nanoparticles to wt% of PDMS in example 1 was modified to be 30:1,20:1,15:1,10:1,5:1,4:1,3:1,2:1,1:1,1:2. After the preparation of the super-blood-dredging wound dressing is completed, the subsequent test is carried out.
As shown in figure 3, different positions are randomly selected, and the contact angle is tested by using a water contact angle meter, so that the test result shows that the prepared super-blood-repellent wound dressing has good super-blood-repellent performance.
Example 4
The fresh pig blood added with the sodium citrate anticoagulant is dripped into the super-blood-repellent wound dressing, after standing for 2 hours at room temperature, the dressing is inclined to enable the blood to slide away, the residual blood on the surface of the wound dressing is observed, as shown in fig. 4, the observation result shows that the super-blood-repellent wound dressing has better long-term blood-repellent capacity.
Example 5
Fresh pig blood added with sodium citrate anticoagulant is used, 20 mu L of the fresh pig blood is dripped onto the super-blood-repellent wound dressing, a thin iron wire is added into the blood, and the blood is stood for 12 hours at room temperature, so that blood is coagulated on the super-blood-repellent wound dressing to form scabs. The eschar release force of the super-phobic wound dressing surface was tested using a universal mechanical tester, as shown in figure 5. Experimental results show that the blood crust breaking force condensed on the surface of the super-blood-repellent wound dressing is extremely small, and secondary wounds are difficult to generate in practical application. And the blood crust release force condensed on the surface of the hydrophobic dressing is obviously larger than that of the super-hydrophobic dressing. (PDMS group is hydrophobic dressing, PDMS particle group is super-hydrophobic group without polymer added)
Example 6
And (3) placing the prepared super-blood-repellent wound dressing on a laser object stage, and programming a punching program by using Ezcad software. The aperture range of the laser drilling is 500 μm, the hole center distance is 2000 μm, and the laser scanning times are 300 times. The laser is turned on to perforate the super-phobic wound dressing to produce an array of hydrophilic spots. The hydrophilic array of the super-phobic wound dressing was recorded by photograph and optical microscopy as shown in fig. 6. The observation result shows that the super-blood-thinning wound dressing is penetrated by high heat of laser, and the hydrophilic dot array is prepared.
Example 7
A super-phobic wound dressing containing a hydrophilic array is placed over a device containing through holes, and a band-aid is prevented from over the dressing for absorbing excess blood that is being drained and compacted with a glass sheet, as shown in fig. 7. The control group is a super-blood-repellent wound dressing without a hydrophilic array and a super-blood-repellent wound dressing without a band-aid. Blood (flow rate 5 mL/min) was injected into the device using a syringe pump, and the blood flowed out of the through-hole of the device and contacted the wound dressing, as shown in fig. 7. Experimental results indicate that the hydrophilic array can draw out excess blood, which can be absorbed by the hydrophilic layer (band-aid).
Example 8
20 Mu L of fresh pig blood added with sodium citrate anticoagulant is dripped on the surface of the super-phobic blood wound dressing, standing and coagulating are carried out at 37 ℃ to form scabs, and the connection part of the scabs and the dressing is observed through an SEM section, so that the super-phobic blood fibers are not infiltrated by blood even under the action of the gravity of the blood, the blood drops can be lifted, and the Cassie state is maintained stable, as shown in figure 8.
Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims. It should be understood that the different dependent claims and the features described herein may be combined in ways other than as described in the original claims. It is also to be understood that features described in connection with separate embodiments may be used in other described embodiments.