Bacterial cellulose-based porous foam dressing and preparation method and application thereof

Abstract

Provided are a bacterial cellulose-based porous foam dressing and a preparation method and application thereof. The preparation method comprises: static fermentation culture of foamed porous microspheres in a strain culture solution, the liquid level of the strain culture solution being 8 to 18 mm higher than the accumulation surface of the foamed porous microspheres, washing and drying the fermentation product to obtain a fermentation product with a double-layer structure, and then subjecting the fermentation product to a high-temperature foaming treatment, followed by a purification treatment to obtain a bacterial cellulose-based porous foam dressing; wherein the foamed porous microspheres are a core-shell structure, the core of which is a foaming agent, and the shell is a thermoplastic polymer material. The bacterial cellulose-based porous foam dressing has excellent mechanical properties and good biocompatibility, and the upper surface has dense waterproof and antibacterial properties, and can be widely used in the field of foam dressings.

Description

Technical Field

[0001] The invention belongs to the technical field of foam dressings and relates to a bacterial cellulose-based porous foam dressing and a preparation method and application thereof. Background Art

[0002] The wound healing process is a continuous dynamic process, which is a process of interaction between cells, cells and cell matrices, and soluble media. In clinical practice, wound healing is mainly based on the use of wound dressings. Currently, global wound dressing products mainly include two parts: traditional dressings that provide a dry healing environment and high-end dressings that provide a moist healing environment. Compared with traditional dressings with many disadvantages, high-end dressings with moisture absorption function based on the theory of moist wound healing are widely accepted as an effective way to accelerate healing and are increasingly valued in the world's medical and health field. Traditional dressings, mainly gauze dressings, generally keep wounds dry, destroy healthy growth factors, and easily adhere to new tissues, causing secondary trauma to the wound when the dressing is removed. In contrast, moist dressings are changed less frequently and can reduce the pain of the wound when they are changed. These dressings have unmatched advantages over traditional dressings in treating chronic wounds that are difficult to heal.

[0003] At present, high-end wet dressings include: hydrogel, hydrocolloid, alginate, foam dressing and transparent dressing. Among them, foam dressing has a good therapeutic effect on wounds with moderate to severe exudation. The porous foam dressing obtained by foaming polyurethane or polyester is more commonly used in clinical practice. It has good hydrophilicity and water absorption, so it can absorb a large amount of liquid; after absorbing the exudate, it will not adhere to the wound, thus avoiding secondary trauma to the wound when the dressing is removed; after absorbing the exudate, it will not break and will not produce odor. However, this type of foam dressing has the following problems in practical application: (1) The foam dressing itself has a porous foaming structure, and it is often necessary to use a secondary dressing (such as a transparent film dressing) to make it waterproof and antibacterial, avoid contamination of the wound by the external environment, and reduce the risk of infection; (2) The porous structure leads to low mechanical properties, which is easy to tear during use, causing wound exposure and infection; (3) As synthetic polymers, the biocompatibility and hydrophilicity of polyurethane or polyester need to be strengthened.

[0004] Bacterial cellulose is a polymer compound formed by glucose connected by β-1,4-glycosidic chains. As an excellent biomaterial, it has unique physical and chemical properties: bacterial cellulose has a natural three-dimensional nano-network structure; high tensile strength and elastic modulus; high hydrophilicity, good air permeability, water absorption, water permeability, extraordinary water retention and high wet strength. A large number of studies have shown that bacterial cellulose has good in vivo and in vitro biocompatibility and biodegradability, which makes bacterial cellulose itself applicable to the biomedical field. There have been reports of using pure bacterial cellulose hydrogel as a dressing abroad, and it has been industrialized for clinical use. Therefore, using bacterial cellulose as the base material of the dressing and utilizing the water absorption properties of bacterial cellulose itself can continuously and effectively absorb wound exudate and metabolites on the basis of ensuring biosafety. At present, clinical bacterial cellulose dressing products such as Xcell are mainly used for mild or moderate exudate wounds. For moderate exudate wounds, the porous structure of bacterial cellulose needs to be modified to increase its absorption rate and liquid absorption.

[0005] For the modification of the porous structure of bacterial cellulose, the methods currently reported include the porogen method, the foaming method and the template method. The porogen method is to use microspheres such as paraffin, alginate, gelatin, etc., and ferment them with strains. This method obtains a porous scaffold with controllable pore size. However, the porogen removal process in this method is relatively cumbersome, the connectivity of the porous scaffold is poor, the mechanical properties are low, and the thickness is difficult to increase. The Chinese invention patent with publication number CN103143058A discloses a paraffin negative template, on which bacterial fibers are fermented and cultured, and after paraffin removal, purification and other treatments, a composite hydrogel tissue engineering cartilage repair scaffold material with biological activity is finally obtained; however, the porous structure of the scaffold material is mainly obtained by the paraffin template method, and the template preparation of this type of method is complicated and it is difficult to completely remove it. A Chinese invention patent with publication number CN104958782A discloses a method of preparing a bacterial cellulose foam material containing large pores by generating oxygen or carbon dioxide gas through the decomposition of hydrogen peroxide or carbonate inside bacterial cellulose, which is suitable for cell adhesion and growth into the material, thereby making the bacterial cellulose more suitable for use as a tissue engineering scaffold; however, this method also faces the problems of difficult to control pore structure, small pore size, and poor mechanical strength.

[0006] Therefore, in practical applications, it is urgent to find a reasonable method to effectively control the pore size while maintaining the original three-dimensional nanofiber network of bacterial cellulose, so as to obtain a bacterial cellulose-based porous foam dressing with a macroporous structure and high mechanical strength. Summary of the invention

[0007] The first object of the present invention is to provide a method for preparing a bacterial cellulose-based porous foam dressing; the second object of the present invention is to provide a bacterial cellulose-based porous foam dressing prepared by the method; the third object of the present invention is to provide the use of the bacterial cellulose-based porous foam dressing in a foam dressing.

[0008] The purpose of the present invention is achieved through the following technical solutions:

[0009] In one aspect, the present invention provides a method for preparing a bacterial cellulose-based porous foam dressing, comprising the following steps:

[0010] The foamed porous microspheres are statically fermented in a strain culture solution, the liquid level of the strain culture solution is 8 to 18 mm higher than the accumulation surface of the foamed porous microspheres, the fermentation product is washed and dried to obtain a double-layer structured fermentation product, and then the fermentation product is subjected to a high-temperature foaming treatment, followed by a purification treatment, to obtain a bacterial cellulose-based porous foam dressing;

[0011] The foamed pore-forming microspheres are of a core-shell structure, wherein the core is a foaming agent and the shell is a thermoplastic polymer material.

[0012] The present invention creatively combines the porogen method with the foaming method. First, the space-occupying effect of the foamed porogenic microspheres is utilized to place the foamed porogenic microspheres and the strain culture solution together in a fermentation container for static fermentation. During the static fermentation process, the liquid level of the strain culture solution is 8 to 18 mm higher than the accumulation surface of the foamed porogenic microspheres. This design can ensure that the bacterial cellulose hydrocoagulant generated during the strain fermentation process can wrap the foamed porogenic microspheres, and at the same time, a layer of pure bacterial cellulose with a thickness of 3 to 12 mm can be fermented on the upper part of the foamed porogenic microspheres. When the fermentation product is freeze-dried or critically dried with carbon dioxide, a bacterial cellulose-based porous foam dressing with a double-layer structure can be formed. Subsequently, during the high-temperature foaming process, the thermoplastic polymer in the outer shell of the foamed porous microspheres melts first and gradually enters the interior of the bacterial cellulose; the foaming agent in the inner core of the foamed porous microspheres generates a large amount of gas under the action of heat, forming a foaming effect and obtaining a porous structure with a larger pore size; the bubbles generated by the foaming agent push the thermoplastic polymer on its surface into the interior of the bacterial cellulose, and with the cooling process, the thermoplastic polymer solidifies to form support for the macroporous structure; finally, a structurally stable bacterial cellulose-based porous foam dressing with a macroporous structure is obtained, in which the bacterial cellulose nanofibers form a three-dimensional network and are evenly distributed inside the thermoplastic polymer.

[0013] The method of the present invention can obtain a bacterial cellulose-based porous foam dressing with a large-pore double-layer structure while maintaining the original nanofiber three-dimensional structure of the bacterial cellulose. The bacterial cellulose-based porous foam dressing has excellent mechanical properties and good biocompatibility, and the upper surface has dense waterproof and antibacterial properties, and can be widely used in the field of foam dressings.

[0014] In the above preparation method, preferably, the foaming agent includes one or more of barium azodicarboxylate, azodicarbonamide, N,N'-dimethyl-N,N'-dinitrosoterephthalamide, benzenesulfonyl hydrazide, p-toluenesulfonyl hydrazide, 4,4'-oxybisbenzenesulfonyl hydrazide and 1,3-benzenedisulfonyl hydrazide, but is not limited thereto. The foaming agent used in the present invention is in powder form, has a specific gravity greater than that of water, and releases gas when heated and decomposed.

[0015] In the above preparation method, preferably, the thermoplastic polymer material includes one or more of polypropylene (PP), nylon (PA), polyurethane (PU), polyester (PET), polylactic acid (PLA) and polyglycolide (PGA), but is not limited thereto. The thermoplastic polymer material used in the present invention is a biodegradable thermoplastic polymer material.

[0016] In the above preparation method, preferably, the particle size of the foamed cellular microspheres is 100-2000 μm; wherein the mass of the foaming agent accounts for 5-20 wt % of the mass of the foamed cellular microspheres.

[0017] In the above-mentioned preparation method, preferably, the preparation method of the foamed cellular microspheres comprises:

[0018] The existing template method or microfluidic method is used to process the thermoplastic polymer material into a thermoplastic hollow microsphere shell structure, and then a microneedle is used to inject a foaming agent into the hollow interior of the microsphere shell structure to obtain a core-shell structure foamed porous microsphere. The preparation process of the hollow microsphere shell structure of the present invention is a conventional operation in the art.

[0019] In the above preparation method, preferably, the strain culture solution is composed of a strain capable of fermenting to obtain bacterial cellulose and a fermentation medium;

[0020] The bacterial strain capable of obtaining bacterial cellulose by fermentation includes one or more of Acetobacter xylinum, Rhizobium, Sarcina, Pseudomonas, Achromobacter, Alcaligenes, Aerobacter and Azotobacter; the number of strains in the bacterial culture solution is 1×10 6 ~1×10 12 Pieces / mL;

[0021] The fermentation medium comprises, based on 100% by weight, 1-5% by weight of glucose, 0.05-0.5% by weight of peptone, 0.05-0.5% by weight of yeast extract, 0.01-0.1% by weight of citric acid, 0.02-0.2% by weight of disodium hydrogen phosphate, 0.01-0.1% by weight of potassium dihydrogen phosphate, 0.5-5% by weight of a viscosity enhancer and the remainder of water; the pH value of the fermentation medium is 4.0-6.0.

[0022] In the above preparation method, preferably, the viscosity enhancer includes one or more of gelatin, water-soluble starch, sodium hyaluronate, sodium alginate, pectin, chitosan, agar and carbomer, but is not limited thereto.

[0023] In the above-mentioned preparation method, preferably, the process of static fermentation culture of the foamed porous microspheres in the strain culture solution comprises:

[0024] The foamed porous microspheres are placed in a culture dish, and a strain culture solution is added and poured into the culture dish until the liquid level of the strain culture solution is 8 to 18 mm higher than the accumulation surface of the foamed porous microspheres. The culture is statically cultured for 1 to 7 days at a fermentation temperature of 30 to 40°C.

[0025] The fermentation product obtained by fermentation has a double-layer structure, wherein the upper layer of the double-layer structure is a simple bacterial cellulose hydrogel with a thickness of 3 to 12 mm; the lower layer is a composite of bacterial cellulose hydrogel and foamed pore-forming microspheres, in which the foamed pore-forming microspheres are evenly distributed.

[0026] The culture dish used in the fermentation process of the present invention has a height of 50 cm and an open glass or metal container at the top; the amount of foamed porous microspheres added is measured by the height of the microspheres naturally accumulated in the fermentation culture dish, which is generally 10 to 30 cm; the amount of strain culture solution used is based on the strain culture solution exceeding the height of the foamed porous microspheres by 8 to 18 mm.

[0027] In the above preparation method, preferably, the process of washing and drying the fermentation product comprises:

[0028] The fermentation products are immersed in anhydrous ethanol and pressed repeatedly, washed with water to remove the residual culture solution to obtain the washed products, and then the washed products are freeze-dried or critical carbon dioxide dried to obtain the dried double-layer structure fermentation products.

[0029] In the above preparation method, preferably, the process of high temperature foaming treatment of the fermentation product comprises:

[0030] The washed and dried fermented product is heated to 90-240°C, kept warm for 5-10 minutes, and then cooled naturally to room temperature. The temperature of 90-240°C is close to the temperature at which the thermoplastic polymer of the foamed porous microsphere shell melts and the foaming agent thermally decomposes.

[0031] In the above preparation method, preferably, the process of purifying the fermentation product after high-temperature foaming treatment comprises:

[0032] The fermentation product after high temperature foaming treatment is immersed in a sodium hydroxide solution for purification, and then washed with water until neutral, endotoxins and excess impurities are removed, and a bacterial cellulose-based porous foam dressing is obtained. When used, the moisture content is controlled by drying or not drying according to actual needs to obtain wet foam dressings or dry foam dressings with various water contents.

[0033] In the above preparation method, preferably, the mass concentration of the sodium hydroxide solution is 3-6wt%; the purification treatment time is 3-12h, and the purification treatment temperature is 60-100°C.

[0034] On the other hand, the present invention also provides a bacterial cellulose-based porous foam dressing, which is prepared by the above-mentioned preparation method.

[0035] In the above-mentioned bacterial cellulose-based porous foam dressing, preferably, the thickness of the bacterial cellulose-based porous foam dressing is 12 to 45 mm, and it has a double-layer structure, the upper layer is a simple bacterial cellulose layer, a microporous structure with an average pore size of 1 to 10 μm composed of 20 to 50 nm bacterial cellulose nanofibers, and a thickness of 3 to 12 mm; the lower layer is a foam layer, which is composed of bacterial cellulose nanofibers and foamed porous microspheres, and the interior is a porous structure with a pore size of 150 to 3000 μm, and the pores are interconnected.

[0036] In another aspect, the present invention also provides use of the bacterial cellulose-based porous foam dressing in a foam dressing.

[0037] Beneficial effects of the present invention:

[0038] The present invention adopts a preparation method combining a porogen method and a foaming method, and while maintaining the three-dimensional network structure of bacterial cellulose, a bacterial cellulose-based porous foam dressing with a large pore size and a double-layer structure is prepared through the dual effects of pore formation and foaming. The bacterial cellulose-based porous foam dressing has better mechanical properties and good biocompatibility, and the upper surface has dense waterproof and antibacterial properties, and can be widely used in the field of foam dressings. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 This is a 50-fold electron microscope image of the bacterial cellulose thermoplastic polymer composite foam material prepared in Example 1 of the present invention.

[0040] Figure 2 This is an electron microscope image at 200 times magnification of the bacterial cellulose thermoplastic polymer composite foam material prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0041] In order to have a clearer understanding of the technical features, purposes and beneficial effects of the present invention, the technical solution of the present invention is now described in detail below, but it should not be construed as limiting the applicable scope of the present invention.

[0042] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0043] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0044] Example:

[0045] The following example provides a method for preparing a bacterial cellulose-based porous foam dressing, which comprises the following steps:

[0046] 1. Preparation of foamed porous microspheres:

[0047] In the following embodiments, the structure of the foamed pore-forming microsphere is a core-shell structure, wherein the core is a foaming agent and the shell is a thermoplastic polymer material. The preparation method of the foamed pore-forming microsphere is: the thermoplastic polymer material is processed into a thermoplastic hollow microsphere shell structure (conventional method in the art) by an existing template method or a microfluidic method, and then the foaming agent is injected into the hollow interior of the microsphere shell structure by a microneedle to obtain a foamed pore-forming microsphere with a core-shell structure. Table 1 is a parameter table of the foaming agent, thermoplastic polymer material, microsphere particle size, dosage, etc. used in the preparation of the foamed pore-forming microspheres in each embodiment.

[0048] Table 1:

[0049]

[0050] 2. Static fermentation culture:

[0051] The foamed cellular microspheres of Examples 1 to 8 were placed in culture dishes for natural stacking, and the height of the natural stacking was 10 cm. The strain culture solution was poured into the culture dish until the liquid level of the strain culture solution was 8 mm higher than the stacking surface of the foamed cellular microspheres. Static fermentation was carried out for 5 days, and the fermentation temperature was controlled at 37°C.

[0052] The culture dish used for the fermentation is a glass culture dish with a height of 50 cm and an open top. The strain culture solution is composed of a strain of Acetobacter xylinum that can ferment to obtain bacterial cellulose and a fermentation medium. The concentration of Acetobacter xylinum is about 1×10 5The fermentation medium comprises, based on 100% by weight, 4wt% of glucose, 0.4wt% of peptone, 0.3wt% of yeast extract, 0.08wt% of citric acid, 0.15wt% of disodium hydrogen phosphate, 0.08wt% of potassium dihydrogen phosphate, 0.5wt% of carbomer and the balance of water; the pH value of the fermentation medium is 4.0.

[0053] The fermentation product has an obvious double-layer structure, the upper layer is pure bacterial cellulose hydrogel, the thickness of the upper layer is about 3mm; the lower layer is a mixture of bacterial cellulose hydrogel and foamed pore-forming microspheres, in which the foamed pore-forming microspheres are evenly distributed.

[0054] 3. Cleaning and drying of fermentation products:

[0055] The fermentation products obtained in Examples 1 to 8 above were immersed in anhydrous ethanol and pressed repeatedly for 3 to 5 minutes, then placed in distilled water for washing 3 to 5 times, and repeated 3 to 7 times to wash away the residue of the culture solution to obtain a purified product; the purified product was then freeze-dried at -20°C for 24 hours to obtain a dried double-layer structure fermentation product.

[0056] 4. High temperature foaming and purification treatment:

[0057] The dried double-layer fermentation products of Examples 1 to 8 were placed in an oven respectively, and the temperatures set in the oven were the high-temperature treatment temperatures corresponding to Examples 1 to 8 in Table 1. The products were treated at this temperature for 10 minutes, and naturally cooled to room temperature with the furnace. The fermentation products after high-temperature foaming treatment were immersed in a sodium hydroxide solution with a mass concentration of 5wt% for purification at a purification temperature of 60°C for 12 hours, and then washed with distilled water until neutral to remove endotoxins and excess impurities, thereby obtaining the bacterial cellulose-based porous foam dressings of Examples 1 to 8.

[0058] Figure 1 This is a 50-fold electron microscope image of the bacterial cellulose thermoplastic polymer composite foam material prepared in Example 1 of the present invention; Figure 2 This is a 200-fold electron microscope image of the bacterial cellulose thermoplastic polymer composite foam material prepared in Example 1 of the present invention. Figure 1 It can be seen that the double-layer structure can be clearly observed in the 50x electron microscope image, in which the upper layer is a pure bacterial cellulose layer, which is a microporous structure with an average pore size of about 5μm and composed of bacterial cellulose nanofibers with an average diameter of about 30nm. Figure 2 It can be seen that the lower layer is the foam layer, which is composed of bacterial cellulose nanofibers and foamed porous microspheres. The interior is a porous structure with a pore size of about 150μm. The pores are evenly distributed and interconnected. The bacterial cellulose nanofibers form a three-dimensional network, evenly distributed inside the thermoplastic polymer.

[0059] Performance test experiment:

[0060] The bacterial cellulose-based porous foam dressing prepared in Example 1 was subjected to the following performance tests:

[0061] (1) Mechanical strength performance test:

[0062] The mechanical strength of the bacterial cellulose-based porous foam dressing was measured, and the sample breaking strength was 50 MPa and the modulus was 400 MPa. The bacterial cellulose-based porous foam dressing of the present invention has better mechanical properties.

[0063] (2) Dressing absorption performance test:

[0064] Water vapor transmission rate test of breathable film dressing: According to YY / T 0471.2 "Test methods for contact wound dressings Part 2: Water vapor transmission rate of breathable film dressings", the water vapor transmission rate of bacterial cellulose-based porous foam dressings was tested. The test results show that: Water vapor transmission rate (MVTR): 1000g·m -2 ·24h -1 ; Absorption rate: 3s can absorb liquid 8 times its own weight; Liquid absorption: 1100g·m -2 ·24h -1 .

[0065] (3) Test of the antibacterial performance of dressings:

[0066] Wet Bacterial Barrier Test: The wet bacterial barrier of bacterial cellulose-based porous foam dressings was tested in accordance with YY / T 0471.5 "Test Methods for Contact Wound Dressings Part 5: Bacterial Barrier". The test results showed that the nutrient broth medium showed clarification within a specific period of time, indicating that the sample met the wet bacterial barrier requirements and had good bacterial barrier properties.

[0067] (4) Dressing water barrier performance test:

[0068] The water barrier of bacterial cellulose-based porous foam dressing was tested according to YY-T 0471.3-2004 "Test Methods for Contact Wound Dressings Part 3: Water Barrier", and a 500mm hydrostatic pressure was applied to the upper surface of the dressing sample for 300s. The test results showed that there was no water seepage on the test filter paper, indicating that it had good water barrier properties.

[0069] (5) Biocompatibility test:

[0070] With reference to the biological evaluation of medical devices in GB / T 16886, the bacterial cellulose-based porous foam dressing was evaluated for cytotoxicity, guinea pig delayed contact sensitization, skin irritation, etc. Biocompatibility evaluation: The intracellular toxicity test was tested in accordance with GB / T 16886-5 "Biological Evaluation of Medical Devices Part 5: In Vitro Cytotoxicity Test"; the guinea pig delayed contact sensitization test was tested in accordance with GB / T 16886-10 "Biological Evaluation of Medical Devices Part 10: Irritation and Delayed Hypersensitivity Test", using the maximum test Magnusson method and Kligman method. The skin irritation test was tested in accordance with GB / T16886-10 "Biological Evaluation of Medical Devices Part 10: Irritation and Delayed Hypersensitivity Test". The test results show that the bacterial cellulose-based porous foam dressing prepared in Example 1 of the present invention has a cytotoxicity of less than level 1, no skin sensitization reaction, no intradermal irritation reaction, and has good biological safety.

Claims

1. A method for preparing a bacterial cellulose-based porous foam dressing, comprising the following steps: The foamed porous microspheres are statically fermented in a strain culture solution, the liquid level of the strain culture solution is 8-18 mm higher than the accumulation surface of the foamed porous microspheres, the fermentation product is washed and dried to obtain a double-layer structure fermentation product, and then the fermentation product is subjected to a high-temperature foaming treatment, followed by a purification treatment, to obtain a bacterial cellulose-based porous foam dressing; The foamed pore-forming microspheres are of a core-shell structure, wherein the core is a foaming agent and the shell is a thermoplastic polymer material; The preparation method of the foamed cellular microspheres comprises: The existing template method or microfluidic method is used to process the thermoplastic polymer material into a thermoplastic hollow microsphere shell structure, and then a microneedle is used to inject a foaming agent into the hollow interior of the microsphere shell structure to obtain a core-shell structured foamed porous microsphere.

2. The preparation method according to claim 1, wherein The foaming agent includes one or more of barium azodicarboxylate, azodicarbonamide, N,N'-dimethyl-N,N'-dinitrosoterephthalamide, benzenesulfonyl hydrazide, p-toluenesulfonyl hydrazide, 4,4'-oxybisbenzenesulfonyl hydrazide and 1,3-benzenedisulfonyl hydrazide.

3. The preparation method according to claim 1, wherein The thermoplastic polymer material includes one or more of polypropylene, nylon, polyurethane, polyester, polylactic acid and polyglycolide.

4. The preparation method according to any one of claims 1 to 3, wherein The particle size of the foamed cellular microspheres is 100-2000 μm; wherein the mass of the foaming agent accounts for 5-20 wt % of the mass of the foamed cellular microspheres.

5. The preparation method according to claim 1, wherein The strain culture solution is composed of a strain capable of fermenting to obtain bacterial cellulose and a fermentation medium; The bacterial strain capable of obtaining bacterial cellulose by fermentation includes one or more of Acetobacter xylinum, Rhizobium, Sarcina, Pseudomonas, Achromobacter, Alcaligenes, Aerobacter and Azotobacter; the number of strains in the bacterial culture solution is 1×10 6 ~1×10 12 Pieces / mL; The fermentation medium comprises, based on 100% by weight, 1-5% by weight of glucose, 0.05-0.5% by weight of peptone, 0.05-0.5% by weight of yeast extract, 0.01-0.1% by weight of citric acid, 0.02-0.2% by weight of disodium hydrogen phosphate, 0.01-0.1% by weight of potassium dihydrogen phosphate, 0.5-5% by weight of a viscosity enhancer and the remainder of water; the pH value of the fermentation medium is 4.0-6.

0.

6. The preparation method according to claim 5, wherein: The viscosity enhancer includes one or more of gelatin, water-soluble starch, sodium hyaluronate, sodium alginate, pectin, chitosan, agar and carbomer.

7. The preparation method according to any one of claims 1, 5 to 6, wherein The process of fermenting the foamed porous microspheres in the strain culture medium includes: The foamed porous microspheres are placed in a culture dish, and the strain culture solution is added and poured into the culture dish until the liquid level of the strain culture solution is 8-18 mm higher than the accumulation surface of the foamed porous microspheres. The culture is statically cultured for 1-7 days at a fermentation temperature of 30-40°C. The fermentation product obtained by fermentation has a double-layer structure, wherein the upper layer of the double-layer structure is a simple bacterial cellulose hydrogel with a thickness of 3 to 12 mm; the lower layer is a composite of bacterial cellulose hydrogel and foamed porous microspheres, in which the foamed porous microspheres are evenly distributed.

8. The preparation method according to any one of claims 1, 5 to 6, wherein: The process of washing and drying the fermentation product comprises: The fermentation products are immersed in anhydrous ethanol and pressed repeatedly, washed with water to remove the residual culture solution to obtain the washed products, and then the washed products are freeze-dried or critical carbon dioxide dried to obtain the dried double-layer structure fermentation products.

9. The preparation method according to claim 7, wherein: The process of washing and drying the fermentation product comprises: The fermentation products are immersed in anhydrous ethanol and pressed repeatedly, washed with water to remove the residual culture solution to obtain the washed products, and then the washed products are freeze-dried or critical carbon dioxide dried to obtain the dried double-layer structure fermentation products.

10. The preparation method according to claim 1 or 9, wherein: The process of high temperature foaming treatment of fermentation products includes: The washed and dried fermentation product is heated to 90-240°C, kept warm for 5-10 minutes, and then naturally cooled to room temperature.

11. The preparation method according to claim 8, wherein: The process of high temperature foaming treatment of fermentation products includes: The washed and dried fermentation product is heated to 90-240°C, kept warm for 5-10 minutes, and then naturally cooled to room temperature.

12. The preparation method according to claim 1 or 11, wherein: The process of purifying the fermentation product after high temperature foaming treatment includes: The fermentation product after high-temperature foaming treatment is immersed in a sodium hydroxide solution for purification, and then washed with water until neutral to obtain a bacterial cellulose-based porous foam dressing.

13. The preparation method according to claim 10, wherein: The process of purifying the fermentation product after high temperature foaming treatment includes: The fermentation product after high-temperature foaming treatment is immersed in a sodium hydroxide solution for purification, and then washed with water until neutral to obtain a bacterial cellulose-based porous foam dressing.

14. The preparation method according to claim 12, wherein: The mass concentration of the sodium hydroxide solution is 3-6wt%; the purification treatment time is 3-12h, and the purification treatment temperature is 60-100°C.

15. The preparation method according to claim 13, wherein: The mass concentration of the sodium hydroxide solution is 3-6wt%; the purification treatment time is 3-12h, and the purification treatment temperature is 60-100°C.

16. A bacterial cellulose-based porous foam dressing, which is prepared by the preparation method according to any one of claims 1 to 15.

17. The bacterial cellulose-based porous foam dressing according to claim 16, wherein: The bacterial cellulose-based porous foam dressing has a thickness of 12~45mm and a double-layer structure. The upper layer is a pure bacterial cellulose layer, which is a microporous structure with an average pore size of 1~10μm and a thickness of 3~12mm, composed of 20~50nm bacterial cellulose nanofibers. The lower layer is a foam layer, which is composed of bacterial cellulose nanofibers and foamed porous microspheres. The interior is a porous structure with a pore size of 150~3000μm, and the pores are interconnected.

18. Use of the bacterial cellulose-based porous foam dressing according to claim 16 or 17 in the preparation of foam dressings.

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