An Intrinsic Conductive Wound Dressing, Its Preparation Method and Application

Abstract

The present invention belongs to the technical field of medical wound care materials, and discloses an intrinsic conductive wound dressing, its preparation method and application. After injecting a dispersion liquid containing quaternary ammonium salt of chitosan, carboxymethyl chitosan and carbon nanotubes into a mold, pre-freezing and freeze-drying are carried out to obtain a carboxymethyl chitosan / quaternary ammonium salt of chitosan / carbon nanotube conductive sponge. Then, a conductive gelatin nanofiber membrane and a conductive chitosan nanofiber membrane are constructed on both surfaces of the conductive sponge, and then steam cross-linking is carried out on it to obtain an intrinsic conductive wound dressing. Finally, after applying it to the wound and controlling the contact between the conductive gelatin nanofiber membrane and the wound, the conductivity of the conductive sponge is monitored in real time, and the exudation amount of the exudate is calculated in real time according to the relationship between the conductivity of the conductive sponge and the exudation amount of the exudate. The conductive sponge prepared by the present invention has high conductivity, excellent liquid absorption and antibacterial properties, and also has biocompatibility and excellent mechanical strength.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical wound care materials, and relates to an intrinsically conductive wound dressing, a preparation method thereof, and an application thereof. Background Art

[0002] A conductive sponge is a dielectric material produced by a polymer composite foaming technology. It is usually prepared by combining ordinary sponge materials (such as polyurethane, polyethylene, etc.) with conductive substances. Common preparation methods include: a mixing foaming method, an impregnation method, and a coating method. The mixing foaming method is to directly add a conductive filler during the process of manufacturing the sponge, so that the sponge itself has conductive properties. The impregnation method is to immerse the sponge material in a solution containing conductive particles (such as silver, nickel, carbon nanotubes, or graphene, etc.), and then perform a drying treatment. The coating method is to deposit metals such as nickel and copper by physical vapor deposition (PVD) or chemical vapor deposition (CVD) technology to form a thin layer of conductive material on the surface of the sponge. Conductive sponges are widely used in the fields of electronic products, the automotive industry, aerospace, etc. due to their good electrical conductivity, flexibility, compression resilience, and electromagnetic shielding properties.

[0003] With the progress of technology, people have begun to attempt to apply conductive sponges in the medical field, but they face some limitations and challenges, which are mainly reflected in: First, conductive sponges need to be in direct contact with the human body in some medical applications, so their biocompatibility is crucial. Conductive sponges prepared by traditional methods may have biocompatibility risks and are prone to cause skin irritation or allergic reactions. Some chemical substances or heavy metals may also remain in the preparation process of some conductive sponges, and these components may pose potential hazards to the health of patients. Second, conductive sponges prepared by traditional methods usually have poor liquid absorption performance and are not suitable for scenarios such as wound dressings that require high liquid absorption. Third, traditional conductive sponges lack antibacterial functions and are difficult to meet the strict requirements for infection control in the medical field. Finally, the preparation methods of traditional conductive sponges are complex, with high requirements for equipment and operations, increasing production costs. For example, the mixing foaming method is complex and cannot be used on a large scale; the coating method involves multiple steps of treatment (such as degreasing, activation, electroplating, etc.); the impregnation method increases production costs due to the use of a large amount of solvents or dispersions, and may also cause environmental pollution problems.

[0004] In summary, although the conductive sponges in the prior art have certain electrical conductivity, they have deficiencies in aspects such as liquid absorption performance, antibacterial performance, and biocompatibility. In order to make conductive sponges play a greater role in the medical field, especially in wound dressings, it is still necessary to overcome the above challenges to achieve wider applications. Summary of the Invention

[0005] The purpose of the present invention is to solve the problems existing in the prior art, and provide an intrinsically conductive wound dressing, a preparation method thereof, and an application thereof.

[0006] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] An intrinsic conductive wound dressing includes a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge, and conductive gelatin nanofiber membranes and conductive chitosan nanofiber membranes respectively located on both of its surfaces. Among them, the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube composite conductive sponge serves as a liquid absorption layer for absorbing exudate; the conductive gelatin nanofiber membrane serves as a contact layer with a porous structure for guiding the rapid penetration of exudate; the conductive chitosan nanofiber membrane serves as an isolation layer, which not only acts as an electrode but also can guide the passage of exudate and has an antibacterial effect for isolating microorganisms.

[0008] The preparation method of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is: after injecting a dispersion liquid containing chitosan quaternary ammonium salt (QCS), carboxymethyl chitosan (CMCS) and carbon nanotubes (CNTs) into a mold, pre-freezing and freeze-drying are carried out in sequence to obtain the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge. Among them, in the dispersion liquid, both the chitosan quaternary ammonium salt and the carboxymethyl chitosan are in a dissolved state and are evenly distributed, and the carbon nanotubes are in a dispersed state;

[0009] The carbon nanotubes are one or more of single-walled carbon nanotubes, double-walled carbon nanotubes and multi-walled carbon nanotubes, the degree of substitution of the chitosan quaternary ammonium salt is 40-85%, and the degree of substitution of the carboxymethyl chitosan is 80-90%;

[0010] The mass ratio of quaternary ammonium chitosan, carboxymethyl chitosan, and carbon nanotubes is 1 - 5:5 - 1:0.02 - 0.15; among them, the setting of this ratio can balance the functions of the three. Among them, quaternary ammonium chitosan provides mechanical strength, carboxymethyl chitosan enhances flexibility and liquid absorption, and carbon nanotubes improve conductivity and mechanical support. An appropriate amount of quaternary ammonium chitosan helps maintain the liquid absorption of the conductive sponge. Because after the conductive sponge is formed, an appropriate amount of quaternary ammonium groups can avoid too strong electrostatic interaction with the carboxyl groups of carboxymethyl chitosan, thus ensuring that the ion-dipole interaction of the carboxyl groups can be fully exerted, enhancing its binding ability to water molecules. An appropriate amount of carboxymethyl chitosan helps maintain the antibacterial property of the conductive sponge because the conductive sponge mainly relies on the quaternary ammonium groups in quaternary ammonium chitosan to play an antibacterial role. Although carboxymethyl chitosan also has certain antibacterial properties due to some unsubstituted amino groups, its antibacterial ability is much lower than that of quaternary ammonium chitosan. By controlling the content of carboxymethyl chitosan, it is possible to avoid excessive carboxyl content, thus ensuring that the positive charge of the quaternary ammonium groups in the quaternary ammonium chitosan molecules can be fully exerted, and further maintaining its excellent antibacterial property. Adding an appropriate amount of carbon nanotubes helps to achieve its uniform dispersion in the conductive sponge and maintain the excellent biocompatibility of the conductive sponge. Due to the high aspect ratio, strong van der Waals force, and large specific surface area of carbon nanotubes, an appropriate amount of carbon nanotubes can avoid forming tight aggregates under the effective coverage of the anchoring groups and solvation chains of the dispersant, thus maintaining a good dispersion state. At the same time, an appropriate amount of carbon nanotubes can avoid the formation of large-sized particles due to aggregation, reducing the risk of mechanical damage to the cell membrane, thus maintaining the excellent biocompatibility of the conductive sponge.

[0011] In the dispersion liquid, the concentration of carbon nanotubes is 2 - 15 mg / mL;

[0012] The preparation process of the dispersion liquid is as follows: After adjusting the pH value of the quaternary ammonium chitosan solution to 2 - 6, it is uniformly mixed with the carboxymethyl chitosan solution to obtain a mixed solution. Then, carbon nanotubes are added to the mixed solution, and after stirring evenly, ultrasonic treatment is carried out to make the carbon nanotubes uniformly dispersed to obtain the dispersion liquid; In the present invention, by adjusting the pH value of the quaternary ammonium chitosan solution to acidic, the amino group (-NH2) in the quaternary ammonium chitosan molecule is protonated to generate a positively charged -NH3 + , and at the same time, its carboxyl group (-COOH) does not ionize under acidic conditions, so it does not carry a negative charge. Thus, quaternary ammonium chitosan carries a positive charge. After mixing it with carboxymethyl chitosan, which also carries a positive charge, no electrostatic interaction will occur, so that the two can be uniformly distributed in the solution.

[0013] The time for pre-freezing is 12 - 48 h, and the time for freeze-drying is 24 - 72 h;

[0014] The antibacterial rate of carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge against Staphylococcus aureus and Escherichia coli is more than 90%, the water absorption rate is 4000-7500% of its own weight, the compression strength is 0.015-0.035MPa, and it has the characteristic that the conductive performance changes detectably with the absorption of liquid.

[0015] The conductive sponge of the invention has excellent conductive performance because carbon nanotubes are added in the process of preparing the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge, and the carbon nanotubes have excellent conductivity.

[0016] The conductive sponge of the present invention has high biocompatibility because chitosan is a natural polysaccharide with good biocompatibility and biodegradability. Chitosan quaternary ammonium salt and carboxymethyl chitosan, as derivatives of chitosan, also retain the biocompatibility.

[0017] The conductive sponge of the present invention has excellent liquid absorption performance. On the one hand, the carboxylic acid group in the carboxymethyl chitosan molecule has strong hydrophilicity. The group can form hydrogen bonds with water molecules to enhance the hydrophilicity of the material. At the same time, the group is easy to dissociate into negative ions (-COO - ), which strongly interacts with water molecules through ion-dipole interaction, further enhancing the hydrophilicity; on the other hand, since chitosan quaternary ammonium salt and carboxymethyl chitosan are uniformly distributed in the dispersion during the preparation of carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge, the conductive sponge has a clear and uniform pore structure, which is beneficial to the rapid absorption and uniform distribution of the liquid.

[0018] The conductive sponge of the present invention has excellent antibacterial properties because the quaternary ammonium salt groups (-N + R3) can bind to negatively charged bacterial cell membranes (such as Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli) through electrostatic adsorption, destroying the integrity of the cell membrane, causing leakage of intracellular substances, and ultimately killing the bacteria; the carboxylic acid group (-COOH) of carboxymethyl chitosan can chelate metal ions (such as Mg) necessary for bacterial growth. 2+ , Ca 2+ ), blocking the bacterial energy metabolism pathway; the nano-needle structure of carbon nanotubes can directly pierce the bacterial cell wall / membrane, causing physical damage.

[0019] The preparation method of the conductive sponge of the invention is simple and has low cost.

[0020] In addition, the conductive sponge of the present invention has excellent mechanical properties because it contains chitosan quaternary ammonium salt, carboxymethyl chitosan and carbon nanotubes. Among them, chitosan quaternary ammonium salt can provide a certain mechanical strength because the quaternary ammonium salt groups (-N+ R3) can be protonated to form a positively charged amino group (-NH 3+ ), which reacts efficiently with the aldehyde group (-CHO) in glutaraldehyde to form a stable Schiff base (-N=CH-) cross-linked network, significantly improving the cross-linking density and three-dimensional skeleton rigidity of the material. Carboxymethyl chitosan can increase the flexibility of the material. The carboxylmethyl group (-CH2COOH) on its molecular chain is highly hydrophilic. After absorbing water, it forms a hydration layer, which weakens the strength of hydrogen bonds between molecular chains, making the molecular chains easier to slide when the material is subjected to force, reducing the risk of brittle fracture. In addition, the steric hindrance effect of the carboxymethyl group reduces the rigid arrangement of the carboxymethyl chitosan molecular chain, giving the material a higher deformation capacity. Carbon nanotubes enhance the mechanical properties of the sponge, making it less likely to deform or damage when subjected to external forces, thereby extending the service life of the sponge and improving its reliability and stability in practical applications.

[0021] If chitosan quaternary ammonium salt and carboxymethyl chitosan of the present invention are replaced with carboxymethyl chitosan quaternary ammonium salt, the mechanical property and liquid absorption performance of the final conductive sponge will be affected.Because chitosan quaternary ammonium salt, carboxymethyl chitosan and carboxymethyl chitosan quaternary ammonium salt are all prepared by carrying out substitution reaction to the amino group on the chitosan molecular chain.Wherein, the degree of substitution of carboxymethyl chitosan quaternary ammonium salt to amino group is higher than chitosan quaternary ammonium salt and carboxymethyl chitosan.Therefore, when carboxymethyl is identical with quaternary ammonium salt group content, carboxymethyl chitosan and quaternary ammonium salt chitosan are used in combination, more amino groups that can be cross-linked under glutaraldehyde steam can be provided than using carboxymethyl chitosan quaternary ammonium salt alone, so the mechanical property of the conductive sponge prepared by the present invention is more excellent.In addition, carboxymethyl and quaternary ammonium salt groups exist simultaneously in the carboxymethyl chitosan quaternary ammonium salt molecular chain, and electrostatic interaction occurs between the two in the dissolution process, causing the excessive entanglement of the molecular chain, thereby can't produce clear hole structure in the sponge forming process, and its liquid absorption performance is adversely affected.

[0022] As the preferred technical solution:

[0023] As described above, the intrinsically conductive wound dressing comprises a conductive gelatin nanofiber membrane consisting of a gelatin nanofiber membrane and carbon nanotubes loaded thereon, wherein the content of carbon nanotubes in the conductive gelatin nanofiber membrane is 0.02-0.15wt%; and a conductive chitosan nanofiber membrane consisting of a chitosan nanofiber membrane and carbon nanotubes loaded thereon, wherein the content of carbon nanotubes in the conductive chitosan nanofiber membrane is 0.02-0.15wt%.

[0024] In the intrinsically conductive wound dressing as described above, the thickness of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is 5-7 mm, the thickness of the conductive gelatin nanofiber membrane is 10-50 μm, and the thickness of the conductive chitosan nanofiber membrane is 10-50 μm.

[0025] The present invention also provides a method for preparing an intrinsically conductive wound dressing as described in any one of the above. After constructing a conductive gelatin nanofiber membrane and a conductive chitosan nanofiber membrane on both surfaces of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge, it is cross-linked with glutaraldehyde vapor (i.e., suspended in a dryer containing a glutaraldehyde solution, and the concentration of the glutaraldehyde solution is 10-25 wt%), and then the intrinsically conductive wound dressing is obtained.

[0026] As a preferred technical solution:

[0027] In the method as described above, the process of constructing a conductive gelatin nanofiber membrane on the surface of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is as follows: First, use a gelatin solution (concentration 10-25 wt%) as the electrospinning solution, and at the same time use the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge as the receiving substrate to perform electrospinning (spinning voltage 15-25 kV) to form a gelatin nanofiber membrane. Then, use a carbon nanotube dispersion (concentration 5-15 mg / mL) as the electrostatic spraying solution, and at the same time use the gelatin nanofiber membrane as the receiving substrate to perform electrostatic spraying (spraying voltage 10-20 kV).

[0028] In the method as described above, the process of constructing a conductive chitosan nanofiber membrane on the surface of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is as follows: First, use a chitosan solution (solvent is water, concentration 1-5 wt%) as the electrospinning solution, and at the same time use the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge as the receiving substrate to perform electrospinning (spinning voltage 5-15 kV) to form a chitosan nanofiber membrane. Then, use a carbon nanotube dispersion (concentration 5-15 mg / mL) as the electrostatic spraying solution, and at the same time use the chitosan nanofiber membrane as the receiving substrate to perform electrostatic spraying (spraying voltage 10-20 kV).

[0029] The present invention also provides a method for real-time monitoring of the exudation amount of exudate. Using an intrinsically conductive wound dressing as described in any one of the above, after applying the intrinsically conductive wound dressing to the wound and controlling the contact between the conductive gelatin nanofiber membrane and the wound, the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is monitored in real time, and the exudation amount of the exudate is calculated in real time according to the relationship between the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge and the exudation amount of the exudate. The relationship is obtained by fitting.

[0030] The main components of wound exudate are water, containing electrolytes, proteins, inflammatory mediators, growth factors, metabolic wastes, and cells, etc. Excessive exudate can lead to an extended inflammatory period, interfere with the activity of growth factors, hinder cell proliferation and migration, damage the extracellular matrix, resulting in problems such as delayed wound healing, increased infection risk, damage to the skin around the wound, and the generation of odor. Therefore, real-time monitoring of wound exudate is crucial for optimizing wound care.

[0031] Traditional wound dressings cannot monitor the water content in real time. Medical staff usually need to replace the dressings regularly to prevent problems such as infection caused by the accumulation of exudate. However, this regular replacement method has certain limitations: if the dressing is replaced prematurely before reaching liquid saturation, it will cause waste of the dressing; if the dressing is not replaced in time after reaching liquid saturation, it will lead to the growth of microorganisms, increasing the risk of infection and disrupting the wound healing process.

[0032] In response to the above problems, various solutions have been proposed in the prior art, but each has its limitations. For example:

[0033] Patent CN218922986U discloses a wound patch with the function of detecting the exudate volume. By arranging a plurality of top detection units on the upper part of the auxiliary material layer, when the exudate infiltrates into a certain top detection unit, the exudate electrically connects the bottom conductive layer and the corresponding top detection unit. After the exudate volume determination module receives the conduction signal, it determines the corresponding exudate volume. However, the detection of this method has a lag, and the exudate needs to reach a specific position to be detected.

[0034] Patent CN215689065U discloses a foam dressing that can monitor the exudate volume of a wound. By arranging a humidity color-changing layer between the foam fitting layer and the outer film, the exudate reacts with the humidity color-changing layer to make it change color. Medical staff judge the amount of exudate according to the degree and area of the color change. The color change detection of this method also has a lag, and the accuracy of judging the exudate volume according to the degree and area of the color change of the color-changing layer is not as high as that of the conductivity detection method.

[0035] Patent CN110548179A discloses a method for monitoring the exudate volume of a wound surface. By using a visual detection camera and a color recognition device to detect the color change of the exudate in real time, and through a picture comparison judgment device for recognition, and judging whether the exudate has abnormal changes according to a preset color difference threshold. However, the visual detection of this method is greatly affected by external factors such as light and color changes, and there may also be a lag.

[0036] Patent CN205598094U discloses a pressure-visible wound exudate management dressing, which senses the upward pressure generated by the liquid-absorbing and liquid-locking layer through a pressure-sensing layer, enabling medical staff to judge whether the liquid-absorbing and liquid-locking layer has reached saturation according to the magnitude of the pressure. The sensitivity and accuracy of the pressure-sensing layer of this method are not as high as those of the conductivity detection method.

[0037] Compared with the above-mentioned prior art, the present invention detects the exudation amount of exudate by measuring the change in the conductivity of the conductive sponge, which has higher directness and sensitivity. Specifically, the present invention uses the contact layer and the isolation layer as electrodes to connect a multimeter to test the conductivity of the conductive sponge. When exudate enters the conductive sponge, since the exudate contains electrolytes, it will affect the conductivity of the conductive sponge. By quantitatively absorbing a certain amount of exudate, an equation between the exudate content and the conductivity of the conductive sponge is fitted, so as to realize the real-time reflection of the water content in the conductive sponge through conductivity.

[0038] The advantage of the present invention is that it can monitor the exudation amount of exudate in real time. Medical staff can timely understand the wound exudation situation according to the monitoring results and reasonably arrange the dressing change time. This not only helps to improve the wound healing effect, but also avoids the inconvenience and resource waste caused by frequent dressing changes, and significantly improves the efficiency and economy of wound care.

[0039] Beneficial effects:

[0040] (1) The conductive sponge of the present invention is prepared from chitosan quaternary ammonium salt, carboxymethyl chitosan and carbon nanotubes by a freeze-drying process, and has high conductivity, excellent liquid-absorbing property and antibacterial property, and at the same time has biocompatibility and excellent mechanical strength. The preparation method is simple and low-cost, and the component synergy is realized by optimizing the material ratio, avoiding the defects of single materials.

[0041] (2) The intrinsic conductive wound dressing of the present invention uses the conductive sponge as the liquid-absorbing layer, the conductive gelatin nanofiber membrane as the contact layer and the conductive chitosan nanofiber membrane as the isolation layer. This sandwich structure design realizes the functions of efficient liquid absorption, rapid liquid diversion and antibacterial isolation. The present invention combines electrospinning, spraying and crosslinking technologies to prepare the intrinsic conductive wound dressing. The process is simple and controllable, and the exudate amount can be monitored in real time through the change in the conductivity of the conductive sponge, improving the nursing accuracy. The dressing is based on natural materials, and has biocompatibility, flexibility and antibacterial property, effectively promoting wound healing.

[0042] (3) The real-time monitoring method of the present invention realizes real-time, sensitive and accurate monitoring of the exudate volume by detecting the dynamic change of the electrical conductivity of the conductive sponge with the absorption amount of the exudate. This method is directly based on the influence of electrolytes in the liquid on the electrical conductivity, avoiding the hysteresis and external interference of traditional methods (such as visual inspection and pressure sensing), without the need for frequent manual inspections, significantly improving the nursing efficiency and reducing resource waste. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 It is a schematic structural diagram of the intrinsic conductive wound dressing prepared in Example B1 of the present invention;

[0044] Figure 2 It is an electron micrograph of the microstructure of the intrinsic conductive wound dressing prepared in Example B1 of the present invention;

[0045] Figure 3 It is a relationship diagram of the moisture content and electrical conductivity of the intrinsic conductive wound dressing prepared in Example B1 of the present invention;

[0046] Figure 4 It is a fitting equation of the moisture content and electrical conductivity of the intrinsic conductive wound dressing prepared in Example B1 of the present invention; in the figure, "Y = 0.00073X + 0.01323" is the fitting equation obtained by fitting, where Y is the electrical conductivity and X is the moisture content;

[0047] Figure 5 It is a schematic diagram of the use of the intrinsic conductive wound dressing prepared in Example B1 of the present invention;

[0048] Wherein, 1 - conductive gelatin nanofiber membrane, 2 - carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge, 3 - conductive chitosan nanofiber membrane, 4 - digital multimeter, 5 - positive electrode wire, 6 - negative electrode wire. DETAILED DESCRIPTION OF THE INVENTION

[0049] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

[0050] To ensure the full disclosure of the performance of the substances used in each example and comparative example, the manufacturers and grades of the substances are specified. Products of other manufacturers and grades that meet the limitations of the present invention are also feasible.

[0051] The test methods for the relevant performance indicators in the following examples and comparative examples are as follows:

[0052] Bacteriostatic rate against Staphylococcus aureus: The carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponges prepared in each example were used as samples respectively. Then, 0.1 g of the sample was added to 40 mL of Staphylococcus aureus suspension (1x10 8 CFU / mL) to obtain a mixture, which was used as the experimental group. The control group was 40 mL of Staphylococcus aureus suspension (1x10 8 CFU / mL) without adding the sample. Then, the suspensions of the control group and the experimental group were co-cultured at 37 °C with a rotation speed of 120 rpm for 6 h. After the co-culture was completed, the suspensions of the experimental group and the control group were diluted 100 times respectively, and then 100 μL of the diluted suspension was taken and spread on two soy casein agar media (manufacturer: Qingdao Haibo Biotechnology Co., Ltd., product number: HBPM034-3), and incubated at 37 °C for 24 h. Then, the colonies of the control group and the experimental group were counted, and the bacteriostatic rate was calculated according to the number of colonies , and its calculation formula is: , where is the number of colonies in the control group, is the number of colonies in the sample group.

[0053] Bacteriostatic rate against Escherichia coli: The carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponges prepared in each example were used as samples respectively. Then, 0.1 g of the sample was added to 40 mL of Escherichia coli suspension (1x10 8 CFU / mL) to obtain a mixture, which was used as the experimental group. The control group was 40 mL of Escherichia coli suspension (1x10 8 CFU / mL) without adding the sample. Then, the suspensions of the control group and the experimental group were co-cultured at 37 °C with a rotation speed of 120 rpm for 6 h. After the co-culture was completed, the suspensions of the experimental group and the control group were diluted 100 times respectively, and then 100 μL of the diluted suspension was taken and spread on two soy casein agar media (manufacturer: Qingdao Haibo Biotechnology Co., Ltd., product number: HBPM034-3), and incubated at 37 °C for 24 h. Then, the colonies of the control group and the experimental group were counted, and the bacteriostatic rate was calculated according to the number of colonies , and its calculation formula is: , where is the number of colonies in the control group, is the number of colonies in the sample group.

[0054] Water absorption ratio: The carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponges prepared in each example were used as samples respectively. Then, after the samples were dried in an oven, the initial mass (g) of the samples at this time was recorded. Then, the samples were immersed in water until the samples completely absorbed the liquid, and the mass of the samples after completely absorbing the liquid was recorded as (g), and then calculate the liquid absorption ratio of the sample according to the calculation formula , and its calculation formula is: .

[0055] Compressive strength: The carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponges prepared in each example were used as samples respectively. Then, the samples were made into cylindrical sponges with a height of 10 mm and a diameter of 10 mm, and the compressive properties of the cylindrical sponges were tested using a universal material testing machine (manufactured by Xieqiang Instrument Manufacturing (Shanghai) Co., Ltd., model CTM2050); among them, the compressive strain was set to 80%, and the compressive strain rate was 5 mm / min.

[0056] Example A1

[0057] A preparation method of a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge, the steps are as follows:

[0058] (1) Preparation of raw materials;

[0059] Carbon nanotubes: single-walled carbon nanotubes, manufactured by Shanghai Titan Co., Ltd., numbered 014262210;

[0060] Chitosan quaternary ammonium salt: degree of substitution is 45%;

[0061] Carboxymethyl chitosan: degree of substitution is 85%;

[0062] HCl aqueous solution: concentration is 2M;

[0063] Water;

[0064] (2) First, add HCl aqueous solution to the chitosan quaternary ammonium salt solution (obtained by uniformly mixing chitosan quaternary ammonium salt and water) to adjust its pH to 4, then uniformly mix it with the carboxymethyl chitosan solution (obtained by uniformly mixing carboxymethyl chitosan and water) to obtain a mixed solution. Then, add carbon nanotubes to the mixed solution, stir evenly, and ultrasonically disperse for 30 min at a power of 800 W to obtain a dispersion; among them, in the dispersion, the concentration of carbon nanotubes is 8 mg / mL, and the mass ratio of chitosan quaternary ammonium salt, carboxymethyl chitosan, and carbon nanotubes is 3:2:0.05;

[0065] (3) After injecting the dispersion in step (2) into a 24-well plate mold, perform pre-freezing and freeze-drying in sequence to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge; among them, the pre-freezing temperature is -40 °C, the pre-freezing time is 12 h, the freeze-drying temperature is -50 °C, and the freeze-drying time is 48 h.

[0066] The antibacterial rates of the finally prepared carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge against Staphylococcus aureus and Escherichia coli are 93% and 94% respectively. The water absorption ratio is 5500% of its own weight, the compressive strength is 0.03 MPa, and it has the characteristic that the electrical conductivity changes detectably with the absorption of liquid.

[0067] Example A2

[0068] A preparation method of a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge comprises the following steps:

[0069] (1) Preparation of raw materials;

[0070] Carbon nanotubes: double-walled carbon nanotubes, manufactured by Beijing Huawei Ruike Chemical Technology Co., Ltd., with the number HWM022082;

[0071] Chitosan quaternary ammonium salt: degree of substitution is 40%;

[0072] Carboxymethyl chitosan: degree of substitution is 80%;

[0073] HCl aqueous solution: concentration is 3M;

[0074] Water;

[0075] (2) First, add HCl aqueous solution to the chitosan quaternary ammonium salt solution (obtained by uniformly mixing chitosan quaternary ammonium salt and water) to adjust its pH to 2, then uniformly mix it with the carboxymethyl chitosan solution (obtained by uniformly mixing carboxymethyl chitosan and water) to obtain a mixed solution. Then add carbon nanotubes to the mixed solution, stir evenly and ultrasonically disperse for 15 min at a power of 700 W to obtain a dispersion; wherein, in the dispersion, the concentration of carbon nanotubes is 2 mg / mL, and the mass ratio of chitosan quaternary ammonium salt, carboxymethyl chitosan and carbon nanotubes is 1:5:0.02;

[0076] (3) After injecting the dispersion in step (2) into a 24-well plate mold, perform pre-freezing and freeze-drying in sequence to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge; wherein, the pre-freezing temperature is -40 °C, the pre-freezing time is 24 h, the freeze-drying temperature is -40 °C, and the freeze-drying time is 24 h.

[0077] The antibacterial rates of the finally prepared carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge against Staphylococcus aureus and Escherichia coli are 99% and 99% respectively. The water absorption ratio is 4000% of its own weight, the compressive strength is 0.015 MPa, and it has the characteristic that the electrical conductivity changes detectably with the absorption of liquid.

[0078] Comparative Example 1

[0079] A preparation method of a conductive sponge is basically the same as that of Example A2, except that: the quaternary ammonium salt of chitosan is replaced by an equal mass of carboxymethyl chitosan (the same as in Example A2).

[0080] The antibacterial rate of the finally prepared conductive sponge against Staphylococcus aureus is 45%, the antibacterial rate against Escherichia coli is 43%, the water absorption ratio is 8500% of its own weight, and the compressive strength is 0.009 MPa.

[0081] Comparative Example 2

[0082] A preparation method of a conductive sponge is basically the same as that of Example A2, except that: the carboxymethyl chitosan is replaced by an equal mass of quaternary ammonium salt of chitosan (the same as in Example A2).

[0083] The antibacterial rate of the finally prepared conductive sponge against Staphylococcus aureus is 99.9%, the antibacterial rate against Escherichia coli is 99.9%, the water absorption ratio is 3500% of its own weight, and the compressive strength is 0.0095 MPa.

[0084] By comparing Example A2, Comparative Example 1, and Comparative Example 2, it can be seen that the antibacterial performance and mechanical properties of the conductive sponge prepared from pure carboxymethyl chitosan are significantly reduced, while the water absorption ratio is significantly increased; the water absorption ratio and mechanical properties of the conductive sponge prepared from pure quaternary ammonium salt of chitosan are significantly reduced, but the antibacterial performance is significantly improved. This is because carboxymethyl chitosan can bind to water molecules through a large number of carboxyl groups on its molecular chain, thus greatly increasing the water absorption ratio of the conductive sponge. However, since only a small amount of amino groups on its molecular chain provide antibacterial effects, the antibacterial ability is significantly reduced; the quaternary ammonium salt of chitosan contains a large number of quaternary ammonium salt groups, which have excellent antibacterial effects, resulting in a significant improvement in antibacterial performance. However, it lacks water molecule binding sites, resulting in a decrease in the water absorption ratio; a single component of carboxymethyl chitosan or quaternary ammonium salt of chitosan cannot form electrostatic interactions, resulting in a decrease in the mechanical properties of the single-component conductive sponge compared to the two-component conductive sponge.

[0085] Example A3

[0086] A preparation method of a carboxymethyl chitosan / quaternary ammonium salt of chitosan / carbon nanotube conductive sponge is as follows:

[0087] (1) Preparation of raw materials;

[0088] Carbon nanotubes: multi-walled carbon nanotubes, manufactured by Shanghai Merck Chemical Technology Co., Ltd., product number MKL-G991390;

[0089] Quaternary ammonium salt of chitosan: degree of substitution is 85%;

[0090] Carboxymethyl chitosan: degree of substitution is 90%;

[0091] Aqueous HCl solution: concentration is 4 M;

[0092] Water;

[0093] (2) First, add the aqueous HCl solution to the chitosan quaternary ammonium salt solution (obtained by uniformly mixing chitosan quaternary ammonium salt and water) to adjust its pH to 6, and then uniformly mix it with the carboxymethyl chitosan solution (obtained by uniformly mixing carboxymethyl chitosan and water) to obtain a mixed solution. Then, add carbon nanotubes to the mixed solution, stir evenly, and ultrasonically disperse it at a power of 1000 W for 30 min to obtain a dispersion; wherein, in the dispersion, the concentration of carbon nanotubes is 10 mg / mL, and the mass ratio of chitosan quaternary ammonium salt, carboxymethyl chitosan, and carbon nanotubes is 5:1:0.15;

[0094] (3) After injecting the dispersion in step (2) into a 12-well plate mold, perform pre-freezing and freeze-drying in sequence to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge; wherein, the temperature of pre-freezing is -20 °C, the time of pre-freezing is 48 h, the temperature of freeze-drying is -50 °C, and the time of freeze-drying is 72 h.

[0095] The finally prepared carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge has an antibacterial rate of 91% against Staphylococcus aureus, an antibacterial rate of 93% against Escherichia coli, a water absorption ratio of 7500% of its own weight, a compressive strength of 0.03 MPa, and has the characteristic that its electrical conductivity changes detectably with the absorption of liquid.

[0096] Example A4

[0097] A preparation method of a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge, the steps are as follows:

[0098] (1) Preparation of raw materials;

[0099] Carbon nanotubes: composed of single-walled carbon nanotubes (manufacturer: Shanghai Titan Co., Ltd., number: 014262210) and double-walled carbon nanotubes (manufacturer: Beijing Huawei Ruike Chemical Technology Co., Ltd., number: HWM022082) with a mass ratio of 1:1;

[0100] Chitosan quaternary ammonium salt: degree of substitution is 60%;

[0101] Carboxymethyl chitosan: degree of substitution is 85%;

[0102] Aqueous HCl solution: concentration is 5 M;

[0103] Water;

[0104] (2) First, add HCl aqueous solution to the chitosan quaternary ammonium salt solution (obtained by uniformly mixing chitosan quaternary ammonium salt and water) to adjust its pH to 5, and then uniformly mix it with the carboxymethyl chitosan solution (obtained by uniformly mixing carboxymethyl chitosan and water) to obtain a mixed solution. Then, add carbon nanotubes to the mixed solution, stir evenly, and ultrasonically disperse it at a power of 1200W for 45 min to obtain a dispersion. Among them, in the dispersion, the concentration of carbon nanotubes is 15 mg / mL, and the mass ratio of chitosan quaternary ammonium salt, carboxymethyl chitosan, and carbon nanotubes is 2:3:0.1;

[0105] (3) After injecting the dispersion in step (2) into a 12-well plate mold, perform pre-freezing and freeze-drying in sequence to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge. Among them, the pre-freezing temperature is -40 °C, the pre-freezing time is 12 h, the freeze-drying temperature is -60 °C, and the freeze-drying time is 48 h.

[0106] The final prepared carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge has an antibacterial rate of 95% against Staphylococcus aureus, an antibacterial rate of 96% against Escherichia coli, a water absorption ratio of 6500% of its own weight, a compressive strength of 0.025 MPa, and has the characteristic that its electrical conductivity changes detectably with the absorption of liquid.

[0107] Example A5

[0108] A preparation method of a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is as follows:

[0109] (1) Preparation of raw materials;

[0110] Carbon nanotubes: composed of single-walled carbon nanotubes (manufacturer: Shanghai Titan Co., Ltd., number: 014262210) and double-walled carbon nanotubes (manufacturer: Beijing Huawei Ruike Chemical Technology Co., Ltd., number: HWM022082) with a mass ratio of 2:3;

[0111] Chitosan quaternary ammonium salt: degree of substitution is 70%;

[0112] Carboxymethyl chitosan: degree of substitution is 90%;

[0113] HCl aqueous solution: concentration is 6M;

[0114] Water;

[0115] (2) First, add HCl aqueous solution to the chitosan quaternary ammonium salt solution (obtained by uniformly mixing chitosan quaternary ammonium salt and water) to adjust its pH to 3. Subsequently, uniformly mix it with the carboxymethyl chitosan solution (obtained by uniformly mixing carboxymethyl chitosan and water) to obtain a mixed solution. Then, add carbon nanotubes to the mixed solution, stir evenly, and ultrasonically disperse it at a power of 900 W for 30 min to obtain a dispersion; wherein, in the dispersion, the concentration of carbon nanotubes is 6 mg / mL, and the mass ratio of chitosan quaternary ammonium salt, carboxymethyl chitosan, and carbon nanotubes is 1:1:0.03;

[0116] (3) After injecting the dispersion in step (2) into a 24-well plate mold, perform pre-freezing and freeze-drying in sequence to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge; wherein, the temperature of pre-freezing is -20 °C, the time of pre-freezing is 48 h, the temperature of freeze-drying is -50 °C, and the time of freeze-drying is 48 h.

[0117] The finally prepared carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge has an antibacterial rate of 94% against Staphylococcus aureus, an antibacterial rate of 96% against Escherichia coli, a water absorption ratio of 6000% of its own weight, a compressive strength of 0.035 MPa, and has the characteristic that its electrical conductivity changes detectably with the absorption of liquid.

[0118] Example B1

[0119] A preparation method of an intrinsic conductive wound dressing is as follows:

[0120] (1) First, use the chitosan solution (with water as the solvent, a concentration of 3 wt%, the manufacturer of chitosan is Shanghai Titan Scientific Co., Ltd., and the product number is 01123489) as the electrospinning solution, and at the same time, use the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge prepared in Example A1 as the receiving substrate. Electrospin on one side to form a chitosan nanofiber membrane. Then, use the CNTs dispersion (obtained by uniformly mixing CNTs (manufacturer is Shanghai Titan Co., Ltd., number is 014262210) and water, with a concentration of 8 mg / mL) as the electrostatic spraying solution, and at the same time, use the chitosan nanofiber membrane as the receiving substrate to perform electrostatic spraying to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive chitosan nanofiber membrane constructed on one side surface;

[0121] The electrospinning process parameters are: spinning voltage 15 kV, receiving distance 15 cm, electrospinning solution injection speed 1 mL / h, temperature 25 °C, environmental relative humidity 40%, and electrospinning time 3 h;

[0122] The process parameters for electrostatic spraying are: spraying voltage 14 kV, feeding rate 1 mL / h, distance from the nozzle to the collector 6 cm, and spraying time 3 h;

[0123] (2) First, use a gelatin solution (obtained by uniformly mixing gelatin (cold water fish skin gelatin, manufacturer Sigma - Aldrich, grade G7041 - 100G) and water, with a concentration of 12 wt%) as the electrospinning solution. At the same time, use the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive chitosan nanofiber membrane constructed on one side obtained in step (1) as the receiving substrate, and perform electrospinning on the side without the constructed conductive chitosan nanofiber membrane to form a gelatin nanofiber membrane. Then, use a CNTs dispersion (obtained by uniformly mixing CNTs (manufacturer Shanghai Titan Co., Ltd., number 014262210) and water, with a concentration of 8 mg / mL) as the electrostatic spraying solution, and use the gelatin nanofiber membrane as the receiving substrate to perform electrostatic spraying to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with conductive gelatin nanofiber membranes and conductive chitosan nanofiber membranes constructed on both sides;

[0124] The electrospinning process parameters are: spinning voltage 20 kV, receiving distance 10 cm, electrospinning solution injection rate 3 mL / h, temperature 25 °C, environmental relative humidity 40%, and spinning time 3 h;

[0125] The process parameters for electrostatic spraying are: spraying voltage 10 kV, feeding rate 1 mL / h, distance from the nozzle to the collector 6 cm, and spraying time 3 h;

[0126] (3) Suspend the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with conductive gelatin nanofiber membranes and conductive chitosan nanofiber membranes constructed on both sides in a dryer containing a glutaraldehyde solution and perform steam cross - linking at 25 °C for 12 h to obtain the intrinsically conductive wound dressing; among them, the concentration of the glutaraldehyde solution is 20 wt%, and the solvent is water.

[0127] The finally prepared intrinsically conductive wound dressing (its electron micrograph is as shown in Figure 2 and its structure is as shown in Figure 1 ) is composed of a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge 2 and conductive gelatin nanofiber membranes 1 and conductive chitosan nanofiber membranes 3 located on both of its sides respectively;

[0128] The conductive gelatin nanofiber membrane is composed of a gelatin nanofiber membrane and carbon nanotubes loaded on it, and the content of carbon nanotubes in the conductive gelatin nanofiber membrane is 0.13 wt%;

[0129] The conductive chitosan nanofiber membrane is composed of a chitosan nanofiber membrane and carbon nanotubes loaded thereon. The content of carbon nanotubes in the conductive chitosan nanofiber membrane is 0.03 wt%.

[0130] The thickness of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is 5 mm, the thickness of the conductive gelatin nanofiber membrane is 10 μm, and the thickness of the conductive chitosan nanofiber membrane is 10 μm.

[0131] The application of the intrinsic conductive wound dressing is as follows: Figure 5 As shown, after the above-prepared intrinsic conductive wound dressing is applied to the wound and the conductive gelatin nanofiber membrane 1 is in contact with the wound, the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge 2 is monitored in real time (as Figure 3 shown), and the moisture content is calculated in real time according to the relationship between the conductivity and the moisture content of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge. The relationship is obtained by fitting (as Figure 4 shown).

[0132] Example B2

[0133] A preparation method of an intrinsic conductive wound dressing comprises the following steps:

[0134] (1) First, a chitosan solution (the solvent is water, the concentration is 1 wt%, the manufacturer of chitosan is Shanghai Bide Pharmaceutical Technology Co., Ltd., and the product number is BD120608) is used as the electrospinning solution, and at the same time, the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge prepared in Example A2 is used as the receiving substrate. Electrospinning is carried out on one side to form a chitosan nanofiber membrane. Then, a CNTs dispersion liquid (obtained by mixing CNTs (the manufacturer is Shanghai Macklin Biochemical Co., Ltd., and the product number is H835719) and water evenly, and its concentration is 5 mg / mL) is used as the electrostatic spraying solution, and at the same time, the chitosan nanofiber membrane is used as the receiving substrate for electrostatic spraying to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive chitosan nanofiber membrane constructed on one-sided surface;

[0135] The electrospinning process parameters are: spinning voltage 5 kV, receiving distance 12 cm, electrospinning solution injection speed 1.1 mL / h, temperature 23 °C, environmental relative humidity 45%, and electrospinning time 4 h;

[0136] The process parameters of electrostatic spraying are: spraying voltage 10 kV, feeding rate 1.1 mL / h, distance from the nozzle to the collector 7 cm, and spraying time 4 h;

[0137] (2) First, use a gelatin solution (obtained by uniformly mixing gelatin (cold-water fish skin gelatin, manufacturer: Sigma-Aldrich, product number: G7041-500G) and water, with a concentration of 10 wt%) as the electrospinning solution. At the same time, use the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge that constructs the conductive chitosan nanofiber membrane on one side obtained in step (1) as the receiving substrate, and perform electrospinning on the side where the conductive chitosan nanofiber membrane is not constructed to form a gelatin nanofiber membrane. Then, use a CNT dispersion (obtained by uniformly mixing CNTs (manufacturer: Shanghai Macklin Biochemical Co., Ltd., product number: G991390) and water, with a concentration of 5 mg / mL) as the electrostatic spraying solution. At the same time, use the gelatin nanofiber membrane as the receiving substrate and perform electrostatic spraying to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with conductive gelatin nanofiber membranes and conductive chitosan nanofiber membranes constructed on both sides;

[0138] The electrospinning process parameters are: spinning voltage 15 kV, receiving distance 12 cm, electrospinning solution injection speed 1 mL / h, temperature 23 °C, environmental relative humidity 45%, and electrospinning time 4 h;

[0139] The process parameters of electrostatic spraying are: spraying voltage 15 kV, feeding rate 1.1 mL / h, distance from the nozzle to the collector 7 cm, and spraying time 4 h;

[0140] (3) Suspend the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with conductive gelatin nanofiber membranes and conductive chitosan nanofiber membranes constructed on both sides in a dryer containing a glutaraldehyde solution and perform steam cross-linking at 23 °C for 48 h to obtain the intrinsic conductive wound dressing; among them, the concentration of the glutaraldehyde solution is 10 wt%, and the solvent is water.

[0141] The finally prepared intrinsic conductive wound dressing is composed of a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge and conductive gelatin nanofiber membranes and conductive chitosan nanofiber membranes located on both sides thereof;

[0142] The conductive gelatin nanofiber membrane is composed of a gelatin nanofiber membrane and carbon nanotubes loaded thereon, and the content of carbon nanotubes in the conductive gelatin nanofiber membrane is 0.15 wt%;

[0143] The conductive chitosan nanofiber membrane is composed of a chitosan nanofiber membrane and carbon nanotubes loaded thereon, and the content of carbon nanotubes in the conductive chitosan nanofiber membrane is 0.05 wt%;

[0144] The thickness of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is 6 mm, the thickness of the conductive gelatin nanofiber membrane is 30 μm, and the thickness of the conductive chitosan nanofiber membrane is 30 μm.

[0145] The application of the intrinsic conductive wound dressing is as follows: After applying the above-prepared intrinsic conductive wound dressing on the wound and controlling the contact between the conductive gelatin nanofiber membrane and the wound, the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is monitored in real time, and the exudate volume is calculated in real time according to the relationship between the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge and the exudate volume. The relationship is obtained by fitting.

[0146] Example B3

[0147] A preparation method of an intrinsic conductive wound dressing is as follows:

[0148] (1) First, use a chitosan solution (the solvent is water, the concentration is 5 wt%, the manufacturer of chitosan is Beijing Innochem Science & Technology Co., Ltd., and the product number is BD120608) as the electrospinning solution, and at the same time, use the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge prepared in Example A3 as the receiving substrate. Electrospinning is carried out on one side to form a chitosan nanofiber membrane. Then, use a CNTs dispersion (obtained by uniformly mixing CNTs (the manufacturer is Shanghai Merck Chemical Technology Co., Ltd., and the product number is MKL-G991390) and water, and its concentration is 15 mg / mL) as the electrostatic spraying solution, and at the same time, use the chitosan nanofiber membrane as the receiving substrate for electrostatic spraying to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive chitosan nanofiber membrane constructed on one side surface;

[0149] The electrospinning process parameters are: spinning voltage 10 kV, receiving distance 13 cm, electrospinning solution injection speed 1.3 mL / h, temperature 22 °C, environmental relative humidity 50%, and electrospinning time 5 h;

[0150] The process parameters of electrostatic spraying are: spraying voltage 20 kV, feeding rate 1.3 mL / h, distance from the nozzle to the collector 9 cm, and spraying time 5 h;

[0151] (2) First, use a gelatin solution (obtained by uniformly mixing gelatin (porcine skin gelatin, manufacturer: Sigma-Aldrich, product number: V900863-100G) and water, with a concentration of 25 wt%) as the electrospinning solution. At the same time, use the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive chitosan nanofiber membrane constructed on one side obtained in step (1) as the receiving substrate, and perform electrospinning on the side without the constructed conductive chitosan nanofiber membrane to form a gelatin nanofiber membrane. Then, use a CNT dispersion solution (obtained by uniformly mixing CNTs (manufacturer: Shanghai Merck Chemical Technology Co., Ltd., product number: MKL-G991390) and water, with a concentration of 15 mg / mL) as the electrostatic spraying solution. At the same time, use the gelatin nanofiber membrane as the receiving substrate and perform electrostatic spraying to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive gelatin nanofiber membrane and a conductive chitosan nanofiber membrane constructed on both sides;

[0152] The electrospinning process parameters are: spinning voltage 25 kV, receiving distance 15 cm, electrospinning solution injection speed 5 mL / h, temperature 22 °C, environmental relative humidity 50%, and spinning time 5 h;

[0153] The process parameters of electrostatic spraying are: spraying voltage 20 kV, feeding rate 1.3 mL / h, distance from the nozzle to the collector 9 cm, and spraying time 5 h;

[0154] (3) Suspend the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive gelatin nanofiber membrane and a conductive chitosan nanofiber membrane constructed on both sides in a dryer containing a glutaraldehyde solution and perform steam cross-linking at 22 °C for 12 h to obtain the intrinsic conductive wound dressing; among them, the concentration of the glutaraldehyde solution is 25 wt%, and the solvent is water.

[0155] The finally prepared intrinsic conductive wound dressing is composed of a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge and a conductive gelatin nanofiber membrane and a conductive chitosan nanofiber membrane located on both sides thereof;

[0156] The conductive gelatin nanofiber membrane is composed of a gelatin nanofiber membrane and carbon nanotubes loaded thereon, and the content of carbon nanotubes in the conductive gelatin nanofiber membrane is 0.05 wt%;

[0157] The conductive chitosan nanofiber membrane is composed of a chitosan nanofiber membrane and carbon nanotubes loaded thereon, and the content of carbon nanotubes in the conductive chitosan nanofiber membrane is 0.02 wt%;

[0158] The thickness of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is 6 mm, the thickness of the conductive gelatin nanofiber membrane is 40 μm, and the thickness of the conductive chitosan nanofiber membrane is 40 μm.

[0159] The application of the intrinsic conductive wound dressing is as follows: After the above-prepared intrinsic conductive wound dressing is applied to the wound and the contact between the conductive gelatin nanofiber membrane and the wound is controlled, the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is monitored in real time, and the exudate volume is calculated in real time according to the relationship between the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge and the exudate volume. The relationship is obtained by fitting.

[0160] Example B4

[0161] A preparation method of an intrinsic conductive wound dressing is as follows:

[0162] (1) First, use a chitosan solution (with water as the solvent, a concentration of 3 wt%, the manufacturer of chitosan is Shanghai Macklin Biochemical Co., Ltd., and the product number is C804728) as the electrospinning solution, and at the same time, use the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge prepared in Example A4 as the receiving substrate. Electrospinning is carried out on one side to form a chitosan nanofiber membrane. Then, use a CNTs dispersion solution (obtained by mixing CNTs (manufacturer: Shanghai Yuanye Bio-Technology Co., Ltd., product number: T19281) and water evenly, with a concentration of 9 mg / mL) as the electrostatic spraying solution, and at the same time, use the chitosan nanofiber membrane as the receiving substrate for electrostatic spraying to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive chitosan nanofiber membrane constructed on one side surface;

[0163] The electrospinning process parameters are: spinning voltage 12 kV, receiving distance 14 cm, electrospinning solution injection speed 1.5 mL / h, temperature 26 °C, environmental relative humidity 60%, and electrospinning time 6 h;

[0164] The process parameters of electrostatic spraying are: spraying voltage 15 kV, feeding rate 1.5 mL / h, distance from the nozzle to the collector 10 cm, and spraying time 6 h;

[0165] (2) First, use a gelatin solution (obtained by uniformly mixing gelatin (cold water fish skin gelatin, manufacturer: Sigma-Aldrich, product number: G7041-100G) and water, with a concentration of 20 wt%) as the electrospinning solution. At the same time, use the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive chitosan nanofiber membrane constructed on one side obtained in step (1) as the receiving substrate, and electrospin to form a gelatin nanofiber membrane on the side where the conductive chitosan nanofiber membrane is not constructed. Then, use a CNTs dispersion solution (obtained by uniformly mixing CNTs (manufacturer: Shanghai Yuanye Bio-Technology Co., Ltd., product number: T19281) and water, with a concentration of 9 mg / mL) as the electrostatic spraying solution, and use the gelatin nanofiber membrane as the receiving substrate for electrostatic spraying to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive gelatin nanofiber membrane and a conductive chitosan nanofiber membrane constructed on both sides;

[0166] The electrospinning process parameters are: spinning voltage 22 kV, receiving distance 14 cm, electrospinning solution injection speed 4 mL / h, temperature 26 °C, environmental relative humidity 60%, and spinning time 6 h;

[0167] The process parameters of electrostatic spraying are: spraying voltage 18 kV, feeding rate 1.5 mL / h, distance from the nozzle to the collector 10 cm, and spraying time 6 h;

[0168] (3) Suspend the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive gelatin nanofiber membrane and a conductive chitosan nanofiber membrane constructed on both sides in a dryer containing a glutaraldehyde solution and perform steam cross-linking at 26 °C for 24 h to obtain the intrinsic conductive wound dressing; among them, the concentration of the glutaraldehyde solution is 15 wt%, and the solvent is water.

[0169] The finally prepared intrinsic conductive wound dressing is composed of a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge and a conductive gelatin nanofiber membrane and a conductive chitosan nanofiber membrane located on both sides thereof respectively;

[0170] The conductive gelatin nanofiber membrane is composed of a gelatin nanofiber membrane and carbon nanotubes loaded thereon, and the content of carbon nanotubes in the conductive gelatin nanofiber membrane is 0.02 wt%;

[0171] The conductive chitosan nanofiber membrane is composed of a chitosan nanofiber membrane and carbon nanotubes loaded thereon, and the content of carbon nanotubes in the conductive chitosan nanofiber membrane is 0.12 wt%;

[0172] The thickness of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is 7 mm, the thickness of the conductive gelatin nanofiber membrane is 50 μm, and the thickness of the conductive chitosan nanofiber membrane is 50 μm.

[0173] The application of the intrinsic conductive wound dressing is as follows: After applying the prepared intrinsic conductive wound dressing on the wound and controlling the contact between the conductive gelatin nanofiber membrane and the wound, the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is monitored in real time, and the exudate volume is calculated in real time according to the relationship between the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge and the exudate volume. The relationship is obtained by fitting.

[0174] Example B5

[0175] A preparation method of an intrinsic conductive wound dressing is as follows:

[0176] (1) First, use a chitosan solution (with water as the solvent, a concentration of 4 wt%, the manufacturer of chitosan is Shanghai Aladdin Biochemical Technology Co., Ltd., and the product number is C105799) as the electrospinning solution, and at the same time, use the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge prepared in Example A5 as the receiving substrate. Electrospinning is carried out on one side to form a chitosan nanofiber membrane. Then, use a CNTs dispersion solution (obtained by mixing CNTs (manufacturer: Shanghai Naicheng Biotechnology Co., Ltd., brand: S33198) and water evenly, with a concentration of 7 mg / mL) as the electrostatic spraying solution, and at the same time, use the chitosan nanofiber membrane as the receiving substrate for electrostatic spraying to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive chitosan nanofiber membrane constructed on one side surface;

[0177] The electrospinning process parameters are: spinning voltage 13 kV, receiving distance 11 cm, electrospinning solution injection speed 1 mL / h, temperature 24 °C, environmental relative humidity 55%, and electrospinning time 5 h;

[0178] The process parameters of electrostatic spraying are: spraying voltage 16 kV, feeding rate 1 mL / h, distance from the nozzle to the collector 8 cm, and spraying time 5 h;

[0179] (2) First, use a gelatin solution (obtained by uniformly mixing gelatin (porcine skin gelatin, manufacturer: Sigma-Aldrich, product number: V900863-500G) and water, with a concentration of 22 wt%) as the electrospinning solution. At the same time, use the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with a conductive chitosan nanofiber membrane constructed on one side obtained in step (1) as the receiving substrate, and electrospin to form a gelatin nanofiber membrane on the side where the conductive chitosan nanofiber membrane is not constructed. Then, use a CNTs dispersion solution (obtained by uniformly mixing CNTs (manufacturer: Shanghai Naicheng Biotechnology Co., Ltd., product number: S33198) and water, with a concentration of 7 mg / mL) as the electrostatic spraying solution, and use the gelatin nanofiber membrane as the receiving substrate for electrostatic spraying to obtain a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with conductive gelatin nanofiber membranes and conductive chitosan nanofiber membranes constructed on both sides;

[0180] The electrospinning process parameters are: spinning voltage 19 kV, receiving distance 13 cm, electrospinning solution injection speed 4 mL / h, temperature 24 °C, environmental relative humidity 55%, and electrospinning time 5 h;

[0181] The process parameters of electrostatic spraying are: spraying voltage 16 kV, feeding rate 1 mL / h, distance from the nozzle to the collector 8 cm, and spraying time 5 h;

[0182] (3) Suspend the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge with conductive gelatin nanofiber membranes and conductive chitosan nanofiber membranes constructed on both sides in a dryer containing a glutaraldehyde solution and perform steam cross-linking at 24 °C for 24 h to obtain the intrinsic conductive wound dressing; among them, the concentration of the glutaraldehyde solution is 18 wt%, and the solvent is water.

[0183] The finally prepared intrinsic conductive wound dressing is composed of a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge and conductive gelatin nanofiber membranes and conductive chitosan nanofiber membranes located on both sides thereof;

[0184] The conductive gelatin nanofiber membrane is composed of a gelatin nanofiber membrane and carbon nanotubes loaded thereon, and the content of carbon nanotubes in the conductive gelatin nanofiber membrane is 0.1 wt%;

[0185] The conductive chitosan nanofiber membrane is composed of a chitosan nanofiber membrane and carbon nanotubes loaded thereon, and the content of carbon nanotubes in the conductive chitosan nanofiber membrane is 0.15 wt%;

[0186] The thickness of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is 6 mm, the thickness of the conductive gelatin nanofiber membrane is 40 μm, and the thickness of the conductive chitosan nanofiber membrane is 40 μm.

[0187] The application of the intrinsic conductive wound dressing is as follows: after applying the above-prepared intrinsic conductive wound dressing on the wound and controlling the contact between the conductive gelatin nanofiber membrane and the wound, the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is monitored in real time, and the exudate volume is calculated in real time according to the relationship between the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge and the exudate volume. The relationship is obtained by fitting.

Claims

1. An intrinsically conductive wound dressing, characterized in that, It includes a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge, a conductive gelatin nanofiber membrane and a conductive chitosan nanofiber membrane respectively located on its bilateral surfaces; The preparation method of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is as follows: after injecting a dispersion liquid containing chitosan quaternary ammonium salt, carboxymethyl chitosan and carbon nanotubes into a mold, pre-freezing and freeze-drying are carried out in sequence to obtain the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge. Among them, in the dispersion liquid, both chitosan quaternary ammonium salt and carboxymethyl chitosan are in a dissolved state and are evenly distributed, and the carbon nanotubes are in a dispersed state; The carbon nanotubes are one or more of single-walled carbon nanotubes, double-walled carbon nanotubes and multi-walled carbon nanotubes, the substitution degree of the chitosan quaternary ammonium salt is 40-85%, and the substitution degree of the carboxymethyl chitosan is 80-90%; The mass ratio of chitosan quaternary ammonium salt, carboxymethyl chitosan and carbon nanotubes is 1-5:5-1:0.02-0.15; In the dispersion liquid, the concentration of the carbon nanotubes is 2-15mg / mL; The preparation process of the dispersion liquid is as follows: after adjusting the pH value of the chitosan quaternary ammonium salt solution to 2-6, it is uniformly mixed with the carboxymethyl chitosan solution to obtain a mixed solution, and then carbon nanotubes are added to the mixed solution, stirred evenly and then subjected to ultrasonic treatment to obtain the dispersion liquid; The time of pre-freezing is 12-48h, and the time of freeze-drying is 24-72h; The antibacterial rates of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge against Staphylococcus aureus and Escherichia coli are both above 90%, the water absorption ratio is 4000-7500% of its own weight, the compressive strength is 0.015-0.035MPa, and it has the characteristic that the conductivity changes detectably with the absorption of liquid.

2. The intrinsic conductive wound dressing according to claim 1, wherein The conductive gelatin nanofiber membrane is composed of a gelatin nanofiber membrane and carbon nanotubes loaded on it, and the content of carbon nanotubes in the conductive gelatin nanofiber membrane is 0.02-0.15wt%; the conductive chitosan nanofiber membrane is composed of a chitosan nanofiber membrane and carbon nanotubes loaded on it, and the content of carbon nanotubes in the conductive chitosan nanofiber membrane is 0.02-0.15wt%.

3. An intrinsic conductive wound dressing according to claim 1, wherein, The thickness of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is 5-7mm, the thickness of the conductive gelatin nanofiber membrane is 10-50μm, and the thickness of the conductive chitosan nanofiber membrane is 10-50μm.

4. A method for preparing an intrinsic conductive wound dressing according to any one of claims 1 to 3, characterized in that, After constructing a conductive gelatin nanofiber membrane and a conductive chitosan nanofiber membrane on the bilateral surfaces of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge respectively, glutaraldehyde vapor cross-linking is carried out on it to obtain the intrinsic conductive wound dressing.

5. The method according to claim 4, wherein The process of constructing the conductive gelatin nanofiber membrane on the surface of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is as follows: first, using a gelatin solution as the electrospinning solution, and at the same time using the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge as the receiving substrate, electrospinning is carried out to form a gelatin nanofiber membrane, and then using a carbon nanotube dispersion liquid as the electrostatic spraying solution, and at the same time using the gelatin nanofiber membrane as the receiving substrate, electrostatic spraying is carried out.

6. The method according to claim 4, wherein The process of constructing a conductive chitosan nanofiber membrane on the surface of a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is as follows: First, a chitosan solution is used as the electrospinning solution, and at the same time, a carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is used as the receiving substrate to perform electrospinning to form a chitosan nanofiber membrane. Then, a carbon nanotube dispersion is used as the electrostatic spraying solution, and at the same time, the chitosan nanofiber membrane is used as the receiving substrate to perform electrostatic spraying.

7. A method for real-time monitoring of the exudation volume of exudate, characterized in that, When using an intrinsic conductive wound dressing according to any one of claims 1 to 3, after applying the intrinsic conductive wound dressing on the wound and controlling the contact between the conductive gelatin nanofiber membrane and the wound, the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge is monitored in real time, and the exudation amount of the exudate is calculated in real time according to the relationship between the conductivity of the carboxymethyl chitosan / chitosan quaternary ammonium salt / carbon nanotube conductive sponge and the exudation amount of the exudate, and the relationship is obtained by fitting.

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