Multifunctional medical fiber membrane and preparation method and application thereof

Abstract

The present application relates to a kind of multifunctional medical fiber membrane and its preparation method and application, the multifunctional medical fiber membrane is with including poly high molecular material, material with anionic group, collagen and ε-polylysine in it Material is raw material, using the electrospun fiber membrane prepared by conjugated electrospinning technology.This medical fiber membrane has the advantages of electrospun membrane and self-assembly membrane simultaneously, close to the structure of extracellular matrix, can provide a large number of cell contact points, provide better microenvironment for cell adhesion, proliferation, physiological function;It contains collagen and ε-polylysine in composition, can make it have good hydrophilicity and antibacterial property, the addition of material with anionic group makes collagen and ε-polylysine more stably combined on fiber membrane, so that it slowly releases, while its own good characteristics make product can be directly attached in clinical use, more effectively induce cell growth and tissue regeneration, and then effectively promote the repair of wound surface.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a multifunctional medical fiber membrane with antibacterial, anti-adhesion, and repair-promoting properties, its preparation method, and its application. Background Technology

[0002] Common problems encountered in surgery include preventing infection, preventing adhesions, and promoting wound healing. As a result, some biomaterials have emerged, such as anti-adhesion membranes made of polymer materials used in clinical practice, and decellularized animal tissue biomaterials that have appeared in recent years. These products provide good anti-adhesion or promote wound healing after surgery.

[0003] In recent years, with the development of additive manufacturing technology, electrospinning technology, as a simple, economical, and effective method for preparing ultrafine fibers, can produce micro- and nano-scale fibers. Nanofiber structures can effectively mimic tissue engineering scaffolds, closely resembling the structure of the extracellular matrix. Their large specific surface area leads to increased surface energy and activity, resulting in small-size effects and surface and interface effects. This provides numerous cell contact points, creating a better microenvironment for cell adhesion, proliferation, and physiological function, improving protein adsorption, and more effectively inducing cell growth and tissue regeneration. It also facilitates the release of drugs and biological factors. Therefore, patches prepared using electrospinning technology have gradually appeared in clinical applications. However, due to the influence of the spinning materials, these patches are mainly composed of polymers, resulting in a lack of hydrophilicity and biocompatibility. Although some products improve this by adding biomolecular materials such as fibrinogen to the polymers, the amount added is limited by the spinnability of the materials, and the biomolecular materials are inevitably encapsulated within the fiber filaments, affecting performance.

[0004] Furthermore, wounds caused by surgery and trauma are susceptible to microbial infection. Without effective treatment, infection can delay healing. While external wounds can often be treated with topical antibiotics, the risk of infection in internal surgical wounds usually requires preventative antibiotic treatment. However, antibiotic resistance due to overuse has become a widespread and concerning issue. Moreover, medical materials implanted after surgery to prevent adhesions and promote repair often have capsules, making infection difficult to manage even with antibiotics due to the lack of capillaries. In previous years, researchers attempted to use nano-silver in medical materials for antibacterial purposes, but the heavy metal toxicity and cytotoxicity of silver, as well as its skin-darkening effects, have led the National Medical Products Administration to maintain a highly cautious approach to silver ion materials. The search for implantable materials with good antibacterial properties, especially those that simultaneously prevent infection, prevent adhesions, and promote wound repair, remains ongoing.

[0005] Collagen is widely present in human and animal tissues. For example, in connective tissue, besides containing 60-70% water, collagen accounts for about 20-30%. Collagen is one of the main components of the extracellular matrix. Due to its good biocompatibility and degradability, and its ability to construct the extracellular matrix microenvironment, which is conducive to cell adhesion and proliferation, and can induce the differentiation of bone marrow mesenchymal stem cells, collagen exhibits certain biological activity and functionality. Therefore, as an important biomaterial, collagen is widely used in many clinical fields and has high practical application value. The main component of decellularized matrix repair materials used clinically is collagen.

[0006] ε-polylysine is a polycationic polypeptide that can inhibit Gram-negative bacteria, Gram-positive bacteria, fungi, etc. It has a broad antibacterial spectrum and even has a killing effect on some viruses. This substance is a lysine homopolymer produced by microorganisms and is a relatively safe antibacterial agent for the human body. Many countries have already widely used it as a food preservative, and people are gradually trying to develop it into a safe and effective antibacterial material for human use.

[0007] CN110507842A discloses a bacterial cellulose / hyaluronic acid / ε-polylysine functional dressing and its preparation method. The ε-polylysine and hyaluronic acid are bound together by electrostatic forces and fixed within the bacterial cellulose network structure. This invention's functional dressing exhibits high safety, good biocompatibility, and broad-spectrum antibacterial properties. The preparation method is simple, efficient, environmentally friendly, and does not damage the three-dimensional network structure of the bacterial cellulose. However, the drawbacks include an increased risk of contamination and higher production costs due to the electrostatic adsorption process.

[0008] CN111441101A discloses a method for preparing PLGA / ε-polylysine antibacterial nanofibers, comprising: mixing polylactic acid-glycolic acid copolymer with 2,2,2-trifluoroethanol and stirring to obtain a polylactic acid-glycolic acid copolymer solution; adding ε-polylysine to deionized water and stirring to obtain an ε-polylysine solution; mixing the polylactic acid-glycolic acid copolymer solution and the ε-polylysine solution to obtain a PLGA / ε-polylysine mixed solution; and electrospinning the PLGA / ε-polylysine mixed solution to obtain PLGA / ε-polylysine antibacterial nanofibers. The antibacterial nanofibers prepared by this invention exhibit good antibacterial properties and thermal stability. However, to achieve an antibacterial effect on the fiber surface using this preparation method, the ε-polylysine content needs to be increased. Increasing the ε-polylysine content, however, can lead to cytotoxicity. Furthermore, the ε-polylysine encapsulated in the fiber filaments is difficult to release completely, remaining in the body for a prolonged period and diffusing to other tissues over time, resulting in persistent cytotoxicity. Summary of the Invention

[0009] To address the shortcomings of existing technologies, the present invention aims to provide a multifunctional medical fiber membrane with antibacterial, anti-adhesion, and repair-promoting properties, as well as its preparation method and applications.

[0010] To achieve this objective, the present invention employs the following technical solution:

[0011] In a first aspect, the present invention provides a multifunctional medical fiber membrane, characterized in that the multifunctional medical fiber membrane is an electrospun fiber membrane prepared by conjugated electrospinning technology using substances including polymer materials, materials with anionic groups, collagen and ε-polylysine as raw materials.

[0012] Preferably, the multifunctional medical fiber membrane is composed of interwoven nanofibers A and B; nanofiber A includes a polymer material, collagen, and ε-polylysine; and nanofiber B includes a polymer material and a material with anionic groups.

[0013] In the aforementioned conjugated electrospinning technology, two opposing spinnerets spin against each other, and these two spinnerets carry opposite charges. Two opposing spinnerets are charged with high voltages of opposite polarities and simultaneously electrospinned. The solution ejected from the two spinnerets is electrospun to obtain nanofibers with opposite charges. In this invention, these are named nanofiber A (positively charged) and nanofiber B (negatively charged), respectively. They attract each other and bind together to form a neutral nanofiber material. Therefore, nanofiber A, in addition to including polymer materials, collagen, and ε-polylysine, may also include a small amount of materials with anionic groups or other active ingredients, as long as nanofiber A is in a positively charged state overall. Similarly, nanofiber B, in addition to including polymer materials and materials with anionic groups, may also include a small amount of collagen, ε-polylysine, or other active ingredients, as long as nanofiber B is in a negatively charged state overall.

[0014] The medical fiber membrane involved in this invention is prepared using conjugate electrospinning technology. Therefore, the prepared fiber membrane structure can well simulate tissue engineering scaffolds, which is conducive to cell adhesion and growth. Nanofibers A and B are mainly composed of polymer materials, which ensures that the mechanical properties and biological functions of the fiber membrane meet the requirements. As a three-dimensional network structure framework, it can provide good mechanical strength, enabling the nanofiber membrane to withstand certain suture forces without tearing or peeling, and to deform without breaking. Moreover, the three-dimensional network structure framework is conducive to cell adhesion and growth, and can also better isolate and prevent adhesion.

[0015] To improve the hydrophilicity and biocompatibility of the polymer material, this invention also adds a certain amount of collagen to nanofiber A. Collagen has biocompatibility and tissue regeneration and repair functions, and will be continuously released as the material degrades to enhance its repair function.

[0016] To improve the antibacterial properties of polymer materials, this invention also adds a certain amount of ε-polylysine to nanofiber A, which enables the fiber membrane material to inhibit bacteria and eliminate the risk of infection.

[0017] Furthermore, since ε-polylysine and collagen carry cationic groups, this invention specifically adds anionic materials to nanofiber B to better fix them onto the three-dimensional network structure. When the material encounters aqueous solutions or bodily fluids, electrostatic interactions facilitate the relatively stable fixation of ε-polylysine and collagen onto the three-dimensional network structure. This reduces the occurrence of ε-polylysine or collagen burst release during product use, allowing the product to better exert its antibacterial and repair properties at wound sites. Simultaneously, the electrostatic interaction between the anionic material and ε-polylysine and / or collagen better fixes the three-dimensional network structure, replacing the cross-linking fixation effect of cross-linking agents and avoiding the toxic side effects of cross-linking agents. In addition, the addition of anionic materials also enhances the overall antibacterial properties of the material.

[0018] Preferably, the mass percentages of the polymer material, collagen, and ε-polylysine in the nanofiber A are 50-95%, 1-10%, and 1-10%, respectively.

[0019] The specific selection of the polymer content in nanofiber A as 50-95% by mass is because a further decrease in its content would reduce the mechanical properties and three-dimensional structure of the nanofiber membrane, while a further increase would prolong the degradation time of the nanofiber membrane. The specific selection of the collagen content in nanofiber A as 1-10% by mass is because a further decrease in its content would affect the repair performance of the nanofiber membrane, while a further increase would affect its mechanical properties. The specific selection of the ε-polylysine content in nanofiber A as 1-10% by mass is because a further decrease in its content would affect the antibacterial properties of the nanofiber membrane, while a further increase would affect its mechanical properties.

[0020] The mass percentage of the polymer material in the nanofiber A can be selected from 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, etc. Other specific values ​​within this range can also be selected, which will not be elaborated here.

[0021] The mass percentage of collagen in nanofiber A can be selected from 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, etc. Other specific values ​​within this range can also be selected, which will not be elaborated here.

[0022] The mass percentage of ε-polylysine in nanofiber A can be selected from 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, etc. Other specific values ​​within this range can also be selected, and will not be elaborated here.

[0023] Preferably, the mass percentages of the polymeric material and the anionic material in the nanofiber B are 50-95% and 1-10%, respectively.

[0024] The specific mass percentage of the polymer material in nanofiber B is chosen to be 50-95% because a further reduction in its content would decrease the mechanical properties and three-dimensional structure of the nanofiber membrane, while a further increase would prolong the degradation time of the nanofiber membrane. The specific mass percentage of the material with anionic groups in nanofiber B is chosen to be 1-10% because a further reduction in its content would affect the binding of the nanofiber membrane to ε-polylysine and collagen, while a further increase would affect the mechanical properties of the nanofiber membrane.

[0025] The mass percentage of the polymer material in the nanofiber B can be selected from 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, etc. Other specific values ​​within this range can also be selected, which will not be elaborated here.

[0026] The mass percentage of the material with anionic groups in the nanofiber B can be selected as 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, etc. Other specific values ​​within this range can also be selected, and will not be elaborated here.

[0027] Preferably, the mass ratio of nanofiber A to nanofiber B is 1:5-5:1, such as 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, etc. Other specific values ​​within this range can be selected, and will not be elaborated here.

[0028] Preferably, the polymeric material comprises any one or a combination of at least two of polylactic acid, polyglycolic acid, polycaprolactone, polyvinyl alcohol, polylactic-co-glycolic acid copolymer, polyethylene glycol, polytetrafluoroethylene, polyesteramide, or polyurethane; preferably, a combination of polylactic acid and polylactic-co-glycolic acid copolymer.

[0029] The combination of at least two of them is, for example, a combination of polylactic acid and polyglycolic acid, a combination of polycaprolactone and polyvinyl alcohol, a combination of polylactic acid-glycolic acid copolymer and polyethylene glycol, etc. Any other combination can be selected, which will not be described in detail here.

[0030] Preferably, the material with anionic groups includes any one or a combination of at least two of sodium hyaluronate, carboxymethyl cellulose, sodium alginate, chondroitin sulfate, or fibrin; preferably, a combination of sodium alginate and sodium hyaluronate.

[0031] The combination of at least two of them is, for example, the combination of sodium hyaluronate and carboxymethyl cellulose, the combination of sodium alginate and chondroitin sulfate, the combination of chondroitin sulfate and fibrin, etc. Any other combination can be selected, which will not be described in detail here.

[0032] Preferably, the collagen includes any one or a combination of at least two of type I collagen or its active domain, type II collagen or its active domain, and type III collagen or its active domain, more preferably type I collagen or type III collagen.

[0033] Preferably, the molecular weight of the ε-polylysine is 3000-5000, such as 3000, 3200, 3400, 3600, 3800, 4000, 4200, 4300, 4600, 4800 or 5000, more preferably 3600-4600, and even more preferably 3600-4300. Any other specific value within the above range can be selected, and will not be elaborated here.

[0034] The molecular weight of the ε-polylysine involved in this invention is specifically selected to be 3000-5000, preferably 3000-4600, and even more preferably 3600-4300, because the antibacterial activity of ε-polylysine is highest at a molecular weight of 3600-4300, and it loses its activity when its molecular weight is less than 1300.

[0035] In a second aspect, the present invention provides a method for preparing a multifunctional medical fiber membrane as described in the first aspect, the method comprising the following steps:

[0036] (1) Polymer material, collagen and ε-polylysine are mixed and dissolved with solvent to obtain spinning solution A; Polymer material and material with anionic groups are mixed and dissolved with solvent to obtain spinning solution B;

[0037] (2) The spinning solution A and the spinning solution B are conjugate spun and dried to obtain the multifunctional medical fiber membrane.

[0038] The preparation method of the multifunctional medical fiber membrane involved in this invention is simple, the product quality is easy to control, and it can achieve high-efficiency, low-pollution and low-cost industrial production.

[0039] Preferably, the solvent is selected from any one or a combination of at least two of the following: chloroform, dichloromethane, N,N-dimethylformamide, methanol, ethanol, hexafluoroisopropanol, trifluoroacetonitrile, trifluoroacetic acid, formic acid, acetic acid, or acetone.

[0040] The combination of at least two of them is, for example, a combination of chloroform and dichloromethane, a combination of N,N-dimethylformamide and methanol, a combination of hexafluoroisopropanol and trifluoroacetonitrile, etc. Any other combination can be selected, which will not be described in detail here.

[0041] Preferably, the temperature of the conjugate spinning is 15-60℃, such as 15℃, 20℃, 22℃, 25℃, 27℃, 30℃, 32℃, 35℃, 40℃, 50℃, 60℃, etc. Any other specific point value within the above range can be selected, and will not be described in detail here.

[0042] Preferably, the humidity of the conjugate spinning is 25-80%, such as 25%, 30%, 40%, 50%, 60%, 70% or 80%, etc. Any other specific value within the above range can be selected, and will not be elaborated here.

[0043] Preferably, the spinning voltage of the conjugate spinning is 5-28kV, such as 5kV, 8kV, 10kV, 12kV, 15kV, 18kV, 20kV, 22kV, 25kV or 28kV, etc. Any other specific point value within the above range can be selected, and will not be described in detail here.

[0044] Preferably, the distance between the needle of the conjugate spinning and the collector is 5-25cm, such as 5cm, 8cm, 10cm, 15cm, 20cm or 25cm, etc. Any other specific point value within the above range can be selected, and will not be described in detail here.

[0045] Preferably, the flow rate of spinning solution A in the conjugate spinning is 0.01-1.5 mL / h, such as 0.01 mL / h, 0.02 mL / h, 0.05 mL / h, 0.1 mL / h, 0.2 mL / h, 0.5 mL / h, 0.6 mL / h, 0.7 mL / h, 1.0 mL / h, or 1.2 mL / h, etc. Any other specific point value within the above range can be selected, and will not be elaborated here.

[0046] Preferably, the flow rate of the spinning solution B in the conjugate spinning is 0.01-1.5 mL / h, such as 0.01 mL / h, 0.02 mL / h, 0.05 mL / h, 0.1 mL / h, 0.2 mL / h, 0.5 mL / h, 0.6 mL / h, 0.7 mL / h, 1.0 mL / h, or 1.2 mL / h, etc. Any other specific point value within the above range can be selected, and will not be elaborated here.

[0047] Preferably, the drying is natural drying, oven drying, vacuum drying, or freeze drying, with true natural drying being the most preferred; the drying time is 2-48 hours, for example, 2 hours, 3 hours, 4 hours, 10 hours, 15 hours, 20 hours, or 48 hours, etc. Any other specific point value within the above range can be selected, and will not be elaborated here.

[0048] Preferably, after the multifunctional medical fiber membrane is prepared, it is further subjected to surface modification treatment to enhance or increase its function.

[0049] Preferably, the surface modification treatment may include, but is not limited to, crosslinking, plasma, or layer-by-layer self-assembly methods.

[0050] Thirdly, the present invention provides a drug delivery system comprising a drug and a multifunctional medical fiber membrane as described in the first aspect, which serves as a drug carrier.

[0051] Fourthly, the present invention provides a method for preparing a drug delivery system as described in the third aspect, the method comprising: adding a drug to spinning solution A and / or spinning solution B. When both spinning solution A and spinning solution B contain drugs, the types of drugs may be the same or different.

[0052] The medical fiber membrane involved in this invention can also serve as an excellent drug carrier material. By adding different amounts and types of drugs to different spinning solution components, the therapeutic effect can be optimized.

[0053] Compared with the prior art, the present invention has the following beneficial effects:

[0054] This invention utilizes conjugated electrospinning technology to prepare a multifunctional medical fiber membrane by combining ε-polylysine with collagen, anionic materials, and polymers. This allows the medical fiber membrane to possess the advantages of both electrospun and self-assembled membranes, while significantly simplifying the manufacturing process. The multifunctional medical material has a structure similar to the extracellular matrix, resulting in a large specific surface area, which increases its surface energy and activity, thus generating a small-size effect and surface and interface effect. This provides numerous cell contact points, creating a better microenvironment for cell adhesion, proliferation, and physiological function, and improving protein adsorption. The presence of collagen and ε-polylysine in the composition gives the multifunctional medical fiber membrane excellent hydrophilicity and antibacterial properties. The addition of anionic materials allows collagen and ε-polylysine to bind more stably to the fiber membrane, enabling slow release. Furthermore, its excellent properties allow for direct application in clinical settings, effectively inducing cell growth and tissue regeneration, thereby effectively promoting wound repair and significantly expanding its application range. The preparation method of the multifunctional medical fiber membrane involved in this invention is simple, the product quality is easy to control, and it can achieve high-efficiency, low-pollution and low-cost industrial production. Attached Figure Description

[0055] Figure 1 This is an external view of the multifunctional medical fiber membrane involved in this invention;

[0056] Figure 2 This is a diagram showing the results of the inhibition zone test of the material prepared in Comparative Example 1 (where a represents the result of Escherichia coli and b represents the result of Staphylococcus aureus).

[0057] Figure 3 This is a diagram showing the results of the inhibition zone test of the material prepared in Example 1 (where a represents the result of Escherichia coli and b represents the result of Staphylococcus aureus). Detailed Implementation

[0058] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0059] Example 1

[0060] This embodiment provides a multifunctional medical fiber membrane, the preparation method of which is as follows:

[0061] (1) Type I collagen was dissolved in hexafluoroisopropanol, and polylactic acid (PLA) with a weight average molecular weight of 112,000 was slowly dissolved in the collagen solution. ε-polylysine (molecular weight 4,000) was dissolved in acetone and mixed with the above collagen solution. The mass percentage of PLA was 8%, the mass percentage of Type I collagen was 0.6%, and the concentration of ε-polylysine was 1%. After stirring at 25°C, a homogeneous and stable solution was formed, and spinning solution A was obtained.

[0062] (2) Dissolve sodium alginate in acetone, and then add PLA to the solution. The mass percentage of PLA is 1% and the concentration of sodium alginate is 1%, thus obtaining spinning solution B.

[0063] (3) The spinning solution A and the spinning solution B are conjugate spun to prepare nanofiber materials; the electrospinning equipment is used for electrospinning at 25°C and 40% humidity, the spinning feed speed is 0.8 mL / h, the spinning voltage is 13 kV, the spinning distance is 10 cm, the receiving device is a metal drum with a diameter of 10 cm, the rotation speed is 100 rpm, and the needle type is 22G;

[0064] (4) The obtained conjugated nanofiber material is immersed in and naturally air-dried for 4 hours to obtain the multifunctional medical fiber membrane. The appearance of the product is shown in the figure below. Figure 1 As shown.

[0065] Example 2

[0066] This embodiment provides a multifunctional medical fiber membrane, the preparation method of which is as follows:

[0067] (1) Type I collagen was dissolved in hexafluoroisopropanol, and polylactic acid-glycolic acid copolymer (PLGA) with a weight average molecular weight of 120,000 was slowly dissolved in the collagen solution. ε-polylysine (molecular weight 4,000) was dissolved in acetone and mixed with the above collagen solution. The mass percentage of PLGA was 10%, the mass percentage of Type I collagen was 2%, and the concentration of ε-polylysine was 0.2%. After stirring at 25°C, a homogeneous and stable solution was formed, and spinning solution A was obtained.

[0068] (2) Dissolve sodium hyaluronate in formic acid, and then add PLGA with a weight average molecular weight of 120,000 to the solution. The mass percentage of PLGA is 5% and the mass percentage of sodium hyaluronate is 0.2%, thus obtaining spinning solution B.

[0069] (3) The spinning solution A and the spinning solution B are conjugate spun to prepare nanofiber materials; the electrospinning equipment is used for electrospinning at 25°C and 40% humidity, the spinning feed speed is 2mL / h, the spinning voltage is 15kV, the spinning distance is 10cm, the receiving device is a metal drum with a diameter of 10cm, the rotation speed is 100rpm, and the needle type is 22G;

[0070] (4) The obtained conjugated nanofiber material is air-dried for 4 hours to obtain the multifunctional medical fiber membrane.

[0071] Example 3

[0072] This embodiment provides a multifunctional medical fiber membrane. The only difference between this membrane and Example 1 is that sodium alginate is replaced with sodium alginate and sodium hyaluronate in a mass ratio of 3:1, i.e., the concentration of sodium alginate in spinning solution B is 0.75% and the concentration of sodium hyaluronate is 0.25%. All other conditions remain unchanged.

[0073] Example 4

[0074] This embodiment provides a multifunctional medical fiber membrane. The difference in its preparation method compared to Example 1 lies only in that the PLA in spinning solution A is replaced with PLA and PLGA in a 1:1 mass ratio, i.e., the mass percentage of PLA is 4% and the mass percentage of PLGA is 4%; and the PLA in spinning solution B is replaced with PLA and PLGA in a 1:1 mass ratio, i.e., the mass percentage of PLA is 0.5% and the mass percentage of PLGA is 0.5%. All other conditions remain unchanged.

[0075] Example 5

[0076] This embodiment provides a multifunctional medical fiber membrane, which is prepared by performing surface modification treatment on the nanofiber membrane prepared in Example 2, that is, performing layer-by-layer self-assembly of the nanofiber membrane:

[0077] (1) First, immerse the nanofiber membrane in a 0.6% ε-polylysine aqueous solution for 10 min, then rinse it three times in pure water and drain the water.

[0078] (2) The fiber nanofilm was then immersed in a 0.2% sodium hyaluronate aqueous solution for 10 minutes, and then rinsed three times in pure water and drained.

[0079] (3) Repeat steps (1) to (2) three times, and then dry in a vacuum freeze dryer for 4 hours to obtain the multifunctional medical fiber membrane.

[0080] Example 6

[0081] This embodiment provides a multifunctional medical fiber membrane. The only difference between this preparation method and that of Example 2 is that docetaxel is added to spinning solution B and paclitaxel is added to spinning solution A. The concentration of docetaxel in spinning solution B is 1%, and the concentration of paclitaxel in spinning solution A is 1%. After spinning, the membrane is freeze-dried while other conditions remain unchanged.

[0082] Comparative Example 1

[0083] This comparative example provides a nanofiber material whose preparation method differs from that of Example 1 only in that the spinning solution A does not contain ε-polylysine. All other components and contents remain unchanged, as do all other conditions.

[0084] Comparative Example 2

[0085] This comparative example provides a nanofiber material whose preparation method differs from that of Example 1 only in that type I collagen is absent in the spinning solution A. All other conditions remain unchanged.

[0086] Comparative Example 3

[0087] This comparative example provides a nanofiber material whose preparation method differs from that of Example 1 only in that the spinning solution B does not contain sodium alginate, while other components and contents remain unchanged, and other conditions also remain unchanged.

[0088] Comparative Example 4

[0089] This comparative example provides a nanofiber material, the preparation method of which is as follows:

[0090] (1) Polylactic acid (PLA) with a weight average molecular weight of 112,000 was dissolved in acetone at a concentration of 8%. After stirring at 25°C, a homogeneous and stable solution was formed (both spinning solutions A and B were 8% PLA). Conjugate electrospinning was carried out. The electrospinning equipment was set at 25°C and 40% humidity. The solution feed rate was 0.8 mL / h, the spinning voltage was 13 kV, the spinning distance was 10 cm, the receiving device was a metal drum with a diameter of 10 cm, the rotation speed was 100 rpm, and the needle type was 22G. PLA nanofiber membrane was prepared.

[0091] (2) The nanofibers prepared above are air-dried for 4 hours to obtain the final product.

[0092] Evaluation test:

[0093] (1) Scanning electron microscopy observation of the multifunctional medical fiber membranes prepared in Examples 1-6 shows that the nanofiber membranes exhibit a spinning and weaving structure with uniform spinning morphology, dense interweaving, and uniform pores, which is very similar to the structure of the extracellular matrix.

[0094] (2) Antibacterial evaluation

[0095] The nanofiber materials obtained in Examples 1-6 and Comparative Examples 1-4 were cut into samples with a diameter of 17 mm. These samples were placed in tryptophan agar plates coated with Escherichia coli and Staphylococcus aureus and incubated upside down at 35°C for 24 h. The size of the inhibition zone was observed and calculated (each group was tested in triplicate), as shown in Table 1 (data are presented as averages). The antibacterial results of Example 1 are as follows: Figure 3 As shown (a represents the Escherichia coli result, b represents the Staphylococcus aureus result); the antibacterial results of Comparative Example 1 are as follows. Figure 2 As shown (a represents Escherichia coli results, b represents Staphylococcus aureus results).

[0096] Table 1

[0097]

[0098]

[0099] As shown in Table 1, no inhibition zone was generated in the nanofiber membrane without ε-polylysine, while all nanofiber membranes containing ε-polylysine showed inhibition zones. This indicates that the antibacterial effect of the nanofiber membrane is produced by the release of ε-polylysine, and that the natural polymer materials, collagen, and sodium alginate themselves do not inhibit Escherichia coli and Staphylococcus aureus.

[0100] (3) In vitro cytotoxicity test

[0101] After irradiation sterilization, the nanofiber materials obtained in Examples 1-6 and Comparative Examples 1-4 were immersed in DMEM complete culture medium to prepare material extracts. Specifically, 2cm x 3cm nanofiber membranes were cut and arranged in 6cm... 2 Extraction was performed at 37°C for 24 days at a / mL extraction ratio. The cytotoxicity of the nanofiber material was evaluated using an in vitro cytotoxicity assay (MTT). Mouse fibroblast cell line (L929) was injected with 1×10⁻⁶ cells / mL. 5 L929 cells were seeded at a density of [number] cells / mL in 96-well tissue culture plates and cultured for 24 hours. The culture medium was then discarded, and 100 μL of nanofiber material extract was added. The cells were cultured for another 24 hours. The control group was incubated with untreated complete culture medium for 24 hours. An MTT assay was performed, and the absorbance at 570 nm was measured using a microplate reader. The viability of L929 cells was obtained through statistical analysis. The results are shown in Table 2.

[0102] Table 2

[0103] Example 1 84.6 Example 2 97.5 Example 3 91.8 Example 4 88.9 Example 5 90.3 Example 6 93.6 Comparative Example 1 107.4 Comparative Example 2 81.7 Comparative Example 3 83.8 Comparative Example 4 103.9

[0104] As shown in Table 2, the cell viability of the nanofiber membranes in each group was >70%, indicating that the nanofiber membranes have good biocompatibility and no cytotoxicity. ε-polylysine has antibacterial properties but some cytotoxicity; this cytotoxicity can be mitigated by using collagen and polyanionic natural polymers, thus promoting the good biocompatibility of the nanofiber membranes.

[0105] (4) Mechanical properties

[0106] The operating method is as follows: Cut a 6cm long and 1cm wide fiber membrane from Examples 1-6 and Comparative Examples 1-4; measure its thickness with a thickness gauge (measure three times and take the average value), and fill the measured data into the tensile testing machine software; adjust the clamp spacing of the tensile testing machine to 4cm, install the nanofiber membrane on the clamp of the tensile testing machine, so that the upper and lower clamps respectively clamp one end of the nanofiber membrane, keep the fiber membrane vertical and flat, and then tighten the clamp; stretch at a rate of 10mm / min until the fiber membrane breaks, and obtain the test results, as shown in Table 3.

[0107] Table 3

[0108] Example 1 2.318 2773.229 52.907 Example 2 4.256 6509.092 88.581 Example 3 2.338 2900.648 53.059 Example 4 3.400 4829.577 67.340 Example 5 3.987 5399.127 47.121 Example 6 4.174 5968.754 78.168 Comparative Example 1 2.581 3021.802 60.340 Comparative Example 2 2.810 3283.096 63.318 Comparative Example 3 2.510 2843.819 54.571 Comparative Example 4 3.192 3773.229 82.571

[0109] As shown in Table 3, the elongation at break, maximum tensile force, and tensile strength of a material directly affect its application. Elongation at break refers to the ratio of the displacement value at break to the original length, which is a characterization of the material's toughness. Maximum tensile force characterizes the maximum stress of the material. Natural polymer materials, when used as biological scaffolds, can provide support with a tensile strength of 1500 kPa. Therefore, the mechanical properties of the prepared nanofiber membranes can meet the required mechanical strength.

[0110] The applicant declares that this invention illustrates a multifunctional medical fiber membrane, its preparation method, and its application through the above embodiments. However, this invention is not limited to the above embodiments, meaning that this invention does not necessarily rely on the above embodiments for implementation. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of raw materials, additions of auxiliary components, and selection of specific methods, etc., all fall within the protection and disclosure scope of this invention.

[0111] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0112] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

Claims

1. A multifunctional medical fiber membrane, characterized in that, The multifunctional medical fiber membrane is an electrospun fiber membrane prepared by conjugated electrospun technology using substances including polymer materials, materials with anionic groups, collagen and ε-polylysine as raw materials. The multifunctional medical fiber membrane is composed of interwoven nanofibers A and B; nanofiber A includes polymer materials, collagen, and ε-polylysine; nanofiber B includes polymer materials and materials with anionic groups.

2. The multifunctional medical fiber membrane as described in claim 1, characterized in that, The mass percentages of the polymer material, collagen, and ε-polylysine in nanofiber A are 50-95%, 1-10%, and 1-10%, respectively.

3. The multifunctional medical fiber membrane as described in claim 1, characterized in that, The mass percentages of the polymeric material and the material with anionic groups in the nanofiber B are 50-95% and 1-10%, respectively.

4. The multifunctional medical fiber membrane as described in claim 1, characterized in that, The mass ratio of nanofiber A to nanofiber B is 1:5-5:

1.

5. The multifunctional medical fiber membrane as described in claim 1, characterized in that, The polymeric material includes any one or a combination of at least two of polylactic acid, polyglycolic acid, polycaprolactone, polyvinyl alcohol, polylactic acid-glycolic acid copolymer, polyethylene glycol, polytetrafluoroethylene, polyesteramide, or polyurethane.

6. The multifunctional medical fiber membrane as described in claim 1, characterized in that, The polymer material is a combination of polylactic acid and polylactic acid-glycolic acid copolymer.

7. The multifunctional medical fiber membrane as described in claim 1, characterized in that, The anionic material includes any one or a combination of at least two of sodium hyaluronate, carboxymethyl cellulose, sodium alginate, chondroitin sulfate, or fibrin.

8. The multifunctional medical fiber membrane as described in claim 1, characterized in that, The material with anionic groups is a combination of sodium alginate and sodium hyaluronate.

9. The multifunctional medical fiber membrane as described in claim 1, characterized in that, The collagen includes any one or a combination of at least two of the following: type I collagen or its active domain, type II collagen or its active domain, and type III collagen or its active domain.

10. The multifunctional medical fiber membrane as described in claim 1, characterized in that, The collagen is either type I collagen or type III collagen.

11. The multifunctional medical fiber membrane as described in claim 1, characterized in that, The molecular weight of the ε-polylysine is 3000-5000.

12. The multifunctional medical fiber membrane as described in claim 1, characterized in that, The molecular weight of the ε-polylysine is 3600-4600.

13. The multifunctional medical fiber membrane as described in claim 1, characterized in that, The molecular weight of the ε-polylysine is 3600-4300.

14. The method for preparing the multifunctional medical fiber membrane according to any one of claims 1-13, characterized in that, The preparation method includes the following steps: (1) Polymer material, collagen and ε-polylysine are mixed and dissolved with solvent to obtain spinning solution A; Polymer material and material with anionic groups are mixed and dissolved with solvent to obtain spinning solution B; (2) The spinning solution A and the spinning solution B are conjugate spun and dried to obtain the multifunctional medical fiber membrane.

15. The method for preparing the multifunctional medical fiber membrane as described in claim 14, characterized in that, The solvent is selected from any one or a combination of at least two of the following: chloroform, dichloromethane, N,N-dimethylformamide, methanol, ethanol, hexafluoroisopropanol, trifluoroacetonitrile, trifluoroacetic acid, formic acid, acetic acid, or acetone.

16. The method for preparing the multifunctional medical fiber membrane as described in claim 14, characterized in that, The temperature of the conjugate spinning is 15-60℃.

17. The method for preparing the multifunctional medical fiber membrane as described in claim 14, characterized in that, The humidity of the conjugate spinning is 25-80%.

18. The method for preparing the multifunctional medical fiber membrane as described in claim 14, characterized in that, The spinning voltage of the conjugate spinning is 5-28 kV.

19. The method for preparing the multifunctional medical fiber membrane as described in claim 14, characterized in that, The distance between the needle of the conjugate spinning process and the collector is 5-25 cm.

20. The method for preparing the multifunctional medical fiber membrane as described in claim 14, characterized in that, The flow rate of spinning solution A in the conjugate spinning process is 0.01-1.5 mL / h.

21. The method for preparing the multifunctional medical fiber membrane as described in claim 14, characterized in that, The flow rate of spinning solution B in the conjugate spinning process is 0.01-1.5 mL / h.

22. The method for preparing the multifunctional medical fiber membrane as described in claim 14, characterized in that, The drying process includes natural drying, oven drying, vacuum drying, or freeze drying.

23. The method for preparing the multifunctional medical fiber membrane as described in claim 14, characterized in that, The drying process is natural drying.

24. The method for preparing the multifunctional medical fiber membrane as described in claim 14, characterized in that, The drying time is 2-48 hours.

25. The method for preparing the multifunctional medical fiber membrane as described in claim 14, characterized in that, After the multifunctional medical fiber membrane is prepared, it is further subjected to surface modification treatment to enhance or increase its function.

26. The method for preparing the multifunctional medical fiber membrane as described in claim 25, characterized in that, The surface modification treatment may include, but is not limited to, cross-linking, plasma, and layer-by-layer self-assembly methods.

27. A drug delivery system, characterized in that, The drug delivery system includes a drug and a multifunctional medical fiber membrane as a drug carrier, as described in any one of claims 1-13.

28. The method for preparing the drug delivery system as described in claim 27, characterized in that, The preparation method includes adding a drug to spinning solution A and / or spinning solution B.

Images