A multifunctional nanofiber hydrogel and its preparation method and application

Abstract

The present invention relates to a multifunctional nanofiber hydrogel, its preparation method and application. By mass percentage, the components include: 47% - 86.9% of water, 0.1% - 1.0% of cellulose nanocrystals, 1% - 10% of polymer, 2% - 12% of protein, and 10% - 30% of crosslinking agent. The prepared nanofiber hydrogel has a tensile rate of more than 2000% at room temperature and a self-healing time of 5 - 45 s. It not only has the characteristics of high stretchability and rapid healing, but also has high transparency, natural antibacterial property, strong tissue adhesion, biocompatibility and pore structure stability, etc. It can become an ideal new type of medical dressing carrier, avoiding secondary injury and effectively preventing the slipping phenomenon of medical dressings when used at moving joints.

Description

Technical Field

[0001] The present invention belongs to the field of functional hydrogels, and particularly relates to a multifunctional nanofiber hydrogel and its preparation method and application. Background Art

[0002] In daily life, the exposed skin tissue will inevitably encounter bumps and injuries. In addition, the clinically wound erosion, bedsore, and the incision left by surgery all need to be treated multiple times during cleaning. Traditional dressings such as gauze, bandage, cotton wool, etc. will adhere to the wound surface during the wound treatment process, causing secondary injury to the wound, and having little antibacterial effect, resulting in poor use effect. In order to overcome the deficiencies of these dressings, many new medical dressings have begun to be concerned and studied. Among them, hydrogel dressings have attracted special attention because hydrogel dressings can provide a moist environment, have a cool and comfortable feeling, allow gas exchange and absorb wound exudates, and promote rapid wound healing. However, at present, during the use of hydrogel dressings, due to their high water content and poor mechanical properties, it is impossible to select a suitable medical dressing according to problems such as the size and shape of the wound, and it is easy to slip off when used on the wound surface, and auxiliary conditions are required for reinforcement. Therefore, it is urgent to design a multifunctional new medical dressing with characteristics such as high stretchability, rapid healing, good tissue adhesion, biodegradability, natural antibacterial property, and stable pore structure.

[0003] The currently disclosed hydrogels cannot simultaneously meet the requirements of medical dressings with high stretchability, rapid self-healing, and strong tissue adhesion. For example, the invention patent with the publication number CN116808286A discloses a hydrogel medical dressing with inflammation-responsive anti-inflammatory on-demand for skin wound healing and its preparation method, with a maximum deformation of 200% - 500%; the invention patent with the publication number CN112574437B discloses a preparation method of a stretchable hydrogel, a stretchable hydrogel and its application, and the prepared hydrogel is stretched to 1000% - 1200% of its own length, and the self-healing time of the hydrogel is not mentioned above. The invention patent with the publication number CN116813932A discloses a preparation method of an injectable hydrogel based on nanocellulose, and the self-healing effect of the hydrogel is evaluated as good self-healing time ≤ 60s, generally 60s - 300s, and poor healing time > 300s, but the stretchability is not reflected. Although the preparation of these hydrogels has certain stretchability, they do not have self-healing properties at the same time, and the hydrogels with self-healing properties do not show stretchability. The invention patent with the publication number CN116217979A discloses a double-crosslinked self-healing nanocellulose hydrogel and its preparation method, and the maximum stretch of the obtained hydrogel is 452.28%, and it heals within 300s; the invention patent with the publication number CN116712599A discloses a high-stretch antibacterial hydrogel dressing for promoting wound healing, its preparation method and application, and the dressing has a tensile fracture elongation rate of more than 1500% and realizes healing within 240s, but the tissue adhesion of the hydrogel is not mentioned, and the slipping phenomenon that may occur during the use of the medical dressing; the invention patent with the publication number CN114085390B discloses a preparation method of a stretchable supramolecular hydrogel, and the obtained hydrogel is stretched to 1300% of its own length. The fresh cut surfaces of the cut hydrogel are closely contacted, and it is observed that the two parts can autonomously heal into a whole, and the specific healing time is not quantified. Summary of the Invention

[0004] Aiming at the defects of the prior art, the technical problem to be solved by the present invention is to provide a multifunctional nanofiber hydrogel, its preparation method and application. The present invention provides the preparation of a multifunctional nanofiber hydrogel medical dressing, which is developed to have a stretch rate of more than 2000% at room temperature and a self-healing time of 5 - 45s. It not only has the characteristics of high stretchability and rapid healing, but also has the characteristics of high transparency, natural antibacterial, strong tissue adhesion, biocompatibility and pore structure stability at the same time, becoming an ideal new medical dressing carrier and one of the most potential medical materials in the future.

[0005] A nanofiber hydrogel of the present invention, by mass percentage, the components include: 47% - 86.9% of water, 0.1% - 1.0% of cellulose nanocrystals, 1% - 10% of a polymer, 2% - 12% of a macromolecular protein, and 10% - 30% of a crosslinking agent.

[0006] Furthermore, a multifunctional nanofiber hydrogel medical dressing is composed of water, cellulose nanocrystals extracted from cotton and linen plants, macromolecular proteins, and a polymer.

[0007] Preferably, the cellulose nanocrystals are extracted from cotton and linen plants; the polymer is polyvinyl alcohol; the macromolecular protein is one or several of gelatin or gelatin derivatives; the crosslinking agent is sodium tetraborate.

[0008] Furthermore, the sodium tetraborate is a sodium tetraborate decahydrate solution with a concentration of 0.1 - 0.2 M.

[0009] The cotton and linen cellulose nanocrystals form strong hydrogen bonds with the gelatin material, and then combined with the reversible ester bonds formed by polyvinyl alcohol and sodium tetraborate decahydrate solution, and a multifunctional nanofiber hydrogel is prepared by physical and chemical crosslinking, which is suitable for medical dressings for various wounds.

[0010] The degree of alcoholysis of the polyvinyl alcohol is above 78%.

[0011] Further preferably, the degree of alcoholysis of the polyvinyl alcohol is at least one of 78%, 87% - 89%, and 98% - 100%.

[0012] Furthermore, the degree of alcoholysis of polyvinyl alcohol is 78%.

[0013] A preparation method of a nanofibrillar cellulose hydrogel of the present invention includes:

[0014] (1) Mix the polymer and the cellulose nanocrystal suspension, and stir with water bath heating until the polymer is completely dissolved to obtain a first solution;

[0015] (2) Add the macromolecular protein to the first solution in step (1), and stir and dissolve with water bath heating to obtain a second solution;

[0016] (3) Mix the second solution in step (2) with the crosslinking agent, crosslink, and perform high-speed centrifugation to completely defoam to obtain a multifunctional nanofiber hydrogel.

[0017] Preferably, in step (1), the cellulose nanocrystals use cotton and linen plants as raw materials, and natural cellulose nanocrystals are extracted by an acid method combined with high-pressure homogenization;

[0018] Among them, the mass fraction of the acid in the acid method is 10% - 70%, the acid hydrolysis temperature is 35°C - 85°C, and the acid hydrolysis time is 20 min - 60 min; the high-pressure homogenization is carried out 5 - 15 times, and the inlet air pressure gauge during homogenization is below 0.7 MPa, and the maximum pressure value is below 100 MPa; the acid is one or several of inorganic acids and organic acids; the inorganic acid is one or several of sulfuric acid, hydrochloric acid, and phosphoric acid; the organic acid is one or several of oxalic acid, maleic acid, and toluic acid.

[0019] Preferably, in the step (1), the mass fraction of the cellulose nanocrystal suspension is 0.1% - 1.0%, the solvent of the cellulose nanocrystal suspension is water, and further preferably deionized water; the water bath heating and stirring in the step (1) include: the water bath temperature is 85°C - 95°C, the heating time is 60 min - 180 min, and the stirring speed is 100 r / min - 500 r / min.

[0020] Furthermore, in the step (1), the high molecular polymer is added to the cellulose nanocrystal suspension.

[0021] Preferably, the water bath heating and stirring in the step (2) include: the water bath temperature is 55°C - 65°C, the heating time is 30 min - 90 min, and the stirring speed is 100 r / min - 500 r / min.

[0022] Furthermore, in the step (2), the macromolecular protein is added to the first solution in the step (2).

[0023] Preferably, in the step (3), the crosslinking temperature is 35°C - 39°C, the centrifugation speed is 5000 r / min, and the centrifugation time is 10 min - 40 min.

[0024] Furthermore, when the second solution in the step (2) is cooled to 35°C - 39°C in the step (3), it is crosslinked with a sodium tetraborate decahydrate solution and centrifuged at high speed.

[0025] The nanofiber hydrogel prepared by the method of the present invention has an elongation rate of more than 2000%, a self-healing time of 5 - 45 s, and has the advantages of adhesiveness, high transparency, and antibacterial property, and can be used as a medical dressing.

[0026] The present invention provides a drug-loaded hydrogel, and the drug-loaded hydrogel uses the nanofiber hydrogel as a carrier to load drugs.

[0027] The present invention provides an application of the nanofiber hydrogel in a medical dressing.

[0028] The present invention mainly provides a nanofiber hydrogel which uses nanocellulose as a building unit to form an interconnected nanoporous network structure of nanocellulose, enabling it to form a dense hydrogen bond network with water molecules and macromolecular proteins, endowing it with excellent tensile properties, self-healing ability, tissue adhesion, and biocompatibility.

[0029] A multifunctional nanofiber hydrogel of the present invention selects cotton and linen plants with good biocompatibility, biodegradability, and low cost as raw materials to extract cellulose nanocrystals and macromolecular protein gelatin to form hydrogen bonds and tightly combine with the reversible ester bonds formed by polyvinyl alcohol and sodium tetraborate decahydrate solution, and forms a multifunctional nanofiber hydrogel through physical and chemical cross-linking. This preparation method first disperses cellulose nanocrystals at room temperature to prepare a suspension, raises the temperature to fully dissolve the polymer, then lowers the temperature to dissolve natural protein macromolecules, and when the temperature drops to about 37 °C, it undergoes physical and chemical cross-linking with sodium tetraborate decahydrate solution. The prepared multifunctional nanofiber hydrogel dressing not only has high stretchability and rapid self-healing ability, but also has stable tissue adhesion at the moving joints, effectively preventing the medical dressing from slipping during use. At the same time, it has characteristics such as high transparency, natural antibacterial property, biocompatibility, and pore structure stability, and is suitable for the field of new medical dressings.

[0030] The significant advantage of the present invention lies in: selecting cellulose nanocrystals extracted from natural cotton and linen plants as raw materials, preparing a suspension of cellulose nanocrystals, first raising the temperature and then lowering the temperature in turn to fully dissolve the polymer and natural protein macromolecules respectively, and performing physical and chemical cross-linking with sodium tetraborate decahydrate solution at about 37 °C to prepare a nanofiber hydrogel.

[0031] The nanofiber hydrogel prepared by the present invention has a tensile rate of more than 2000% and a self-healing time of 5 - 45 s. It not only has the characteristics of high stretchability and rapid healing, but also has characteristics such as high transparency, natural antibacterial property, strong tissue adhesion, biocompatibility, and stable pore structure, becoming an ideal carrier for new medical dressings.

[0032] Preferably, the present invention uses cellulose nanocrystals extracted from natural cotton and linen plants by an acid method combined with high-pressure homogenization to form dense hydrogen bonds with macromolecular protein gelatin, enhance the reversible ester bonds formed between polyvinyl alcohol and sodium tetraborate decahydrate solution, break through the controllable preparation technology of the pore structure of the nanofiber hydrogel through centrifugation and defoaming, and realize the preparation of a three-dimensional network nanocellulose hydrogel dressing, becoming a highly potential medical drug-loading material.

[0033] Beneficial effects

[0034] (1) The cotton and linen cellulose nanocrystals provided by the present invention serve as a bridge structure in the polymer hydrogel to construct a three-dimensional network structure, filling the interior, playing a defoaming function, enhancing the tissue adhesion and self-healing properties of the hydrogel, becoming an ideal base material for medical dressings, avoiding secondary injuries, and effectively preventing the slipping phenomenon that occurs when the medical dressing is used at the moving joints;

[0035] (2) The multifunctional nanocellulose hydrogel provided by the present invention has a tensile rate of more than 2000%, a self-healing time of 5 - 45 s, and strong tissue adhesion, which can meet the requirement of taking what is needed immediately;

[0036] (3) The method for preparing the multifunctional nanocellulose hydrogel provided by the present invention is simple. First, the temperature is raised and then lowered successively to fully dissolve the polymer and protein macromolecules, and physical and chemical cross-linking is carried out with the sodium tetraborate decahydrate solution, reducing the preparation cost and enabling large-scale batch production. Description of the Drawings

[0037] Figure 1 are the cross-sectional and longitudinal-sectional SEM images (1000×) of a multifunctional nanofiber hydrogel medical dressing prepared in Example 1;

[0038] Figure 2 are the cross-sectional and longitudinal-sectional SEM images (1000×) of a multifunctional nanofiber hydrogel medical dressing prepared in Example 2;

[0039] Figure 3 are the cross-sectional and longitudinal-sectional SEM images (1000×) of a multifunctional nanofiber hydrogel medical dressing prepared in Example 3;

[0040] Figure 4 are the cross-sectional and longitudinal-sectional SEM images (1000×) of a multifunctional nanofiber hydrogel medical dressing prepared in Example 4;

[0041] Figure 5 are the cross-sectional and longitudinal-sectional SEM images (1000×) of a hydrogel dressing prepared in Comparative Example 1;

[0042] Figure 6 are the physical pictures and self-healing times demonstrating the self-healing properties of the multifunctional nanofiber hydrogel medical dressings prepared in Examples 1 - 4 and Comparative Example 1;

[0043] Figure 7 are the physical pictures of the structural stability of the multifunctional nanofiber hydrogel medical dressings prepared in Examples 1 - 4 and Comparative Example 1;

[0044] Figure 8 are the photos showing the adhesion effects of the multifunctional nanofiber hydrogel medical dressing prepared in Example 2 on joint tissues and different materials;

[0045] Figure 9 It is a physical drawing of the stretching of the multifunctional nanofiber hydrogel medical dressing prepared in Example 2;

[0046] Figure 10 It is a microscopic image of the antibacterial effect of the multifunctional nanofiber hydrogel medical dressing prepared in Example 2 against Staphylococcus aureus.

[0047] Figure 11 It is a physical drawing of the residual surface bubbles after centrifugation of the multifunctional nanofiber hydrogel medical dressings prepared in Example 2 and Comparative Example 2-3;

[0048] Figure 12 It is a physical drawing of the transparency qualification of the multifunctional nanofiber hydrogel medical dressings prepared in Example 2 and Comparative Example 4. Detailed implementation manners

[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] The cotton and linen plant raw materials, gelatin, and polyvinyl alcohol (degree of alcoholysis 78%) used in the examples were provided by Yu Yue Home Textiles Co., Ltd.; sodium tetraborate decahydrate was purchased from Aladdin Reagent (Shanghai) Co., Ltd.

[0051] The porous magnetic stirrer used in the examples was from Changzhou Surui Instrument Co., Ltd., model HJ-4A; the constant temperature heating magnetic stirrer and the digital display DC constant speed stirrer were from Jiangsu JinYi Technology Co., Ltd., models DF-104S and JJ-6 respectively; the electric inspection screening machine was from Zibo Hengsen Construction and Installation Engineering Co., Ltd., model HS6277200; the circulating water type multi-purpose vacuum pump was from Changsha Mingjie Instrument Co., Ltd., model SHB-Ⅲ; the centrifuge was from Changsha Yingtai Instrument Co., Ltd., model TGL16; the high-pressure homogenizer was from Suzhou Aisen Pharmaceutical Equipment Co., Ltd., model HPH-L2; the electronic precision balance was from Tianjin Tianma Hengji Instrument Co., Ltd., model 2004B.

[0052] First, the cellulose nanocrystals are extracted from cotton plants in the embodiments of the present invention, and the specific process is as follows:

[0053] First, put the cotton into a 5% hydrogen peroxide solution by mass fraction, oxidize it at 70°C for 2 hours, then neutralize it with deionized water to remove the residual hydrogen peroxide. Put the oxidized cotton fibers into a vacuum drying oven at 45°C for 12 hours. After complete drying, classify them using an 80-mesh electric inspection sieve, and retain the cotton powder that passes through the sieve.

[0054] Prepare sulfuric acid with a mass fraction of 64%. After the sulfuric acid stabilizes to 45°C, continuously add the oxidized cotton powder from the bottle mouth and start stirring. Start timing after all the cotton powder is added. Add deionized water to terminate the reaction after 30 minutes. Wash the excess sulfuric acid and its decomposition products with 10 times the amount of water. After neutralization, use high-pressure homogenization to circulate and homogenize 10 times at an inlet pressure of 0.6 MPa and a pressure value of 800 MPa to obtain cellulose nanocrystals.

[0055] Example 1

[0056] Multifunctional nanofiber hydrogel medical dressing. By mass percentage, the components are: deionized water 68.75%, cellulose nanocrystals 0.25%, polyvinyl alcohol 5%, gelatin 6%, 0.1M sodium tetraborate decahydrate 20%.

[0057] A preparation method of a multifunctional nanofiber hydrogel medical dressing includes the following steps:

[0058] (1) Dissolve sodium tetraborate decahydrate in deionized water to prepare a 0.1M sodium tetraborate decahydrate solution;

[0059] (2) Extract cellulose nanocrystals from cotton and linen plants, disperse them in deionized water, and stir magnetically at room temperature for 20 minutes to prepare a cellulose nanocrystal suspension with a mass fraction of 0.25%;

[0060] (3) Add polyvinyl alcohol to the cellulose nanocrystal suspension obtained in step (2) to prepare 5% of the volume of the cellulose nanocrystal suspension occupied by polyvinyl alcohol. Heat and stir at 90°C until fully dissolved. The heating time is 120 minutes and the stirring speed is 200 r / min;

[0061] (4) Cool the solution obtained in step (3) to 60°C while stirring, add gelatin to prepare 6% of the volume of the cellulose nanocrystal suspension occupied by gelatin. The stirring time is 60 minutes and the stirring speed is 200 r / min;

[0062] (5) Cool the solution obtained in step (4) to 37°C while stirring;

[0063] (6) Slowly drop the 0.1 M sodium tetraborate decahydrate solution prepared in step (1) into the solution, and synthesize the cellulose nanocrystal / polyvinyl alcohol / gelatin / sodium tetraborate decahydrate multifunctional cross-linked hydrogel through physical and chemical cross-linking under the action of a Teflon double-leaf stirrer;

[0064] (7) Centrifuge the hydrogel obtained in step (6) at a speed of 5000 r / min for 20 min to make its cross-linking sufficient, and prepare a new type of medical dressing with high tensile strength, self-healing property, strong tissue adhesion and stable pore structure.

[0065] Example 2

[0066] For the multifunctional nanofiber hydrogel medical dressing, by mass percentage, the components are: deionized water 68.5%, cellulose nanocrystals 0.5%, polyvinyl alcohol 5%, gelatin 6%, 0.1 M sodium tetraborate decahydrate 20%.

[0067] A preparation method of a multifunctional nanofiber hydrogel medical dressing includes the following steps:

[0068] (1) Dissolve sodium tetraborate decahydrate in deionized water to prepare a 0.1 M sodium tetraborate solution

[0069] (2) Extract cellulose nanocrystals from cotton and linen plants, disperse them in deionized water, and magnetically stir for 20 min at room temperature to prepare a cellulose nanocrystal suspension with a mass fraction of 0.5%;

[0070] (3) Add polyvinyl alcohol to the cellulose nanocrystal suspension obtained in step (2) to make the volume fraction of polyvinyl alcohol in the cellulose nanocrystal suspension 5%, and heat and stir at 90 °C until it is fully dissolved. The heating time is 120 min and the stirring speed is 200 r / min;

[0071] (4) Cool the solution obtained in step (3) to 60 °C while stirring, add gelatin to make the volume fraction of gelatin in the cellulose nanocrystal suspension 6%, and the stirring time is 60 min and the stirring speed is 200 r / min;

[0072] (5) Cool the solution obtained in step (4) to 37 °C while stirring;

[0073] (6) Slowly drop the 0.1 M sodium tetraborate decahydrate solution prepared in step (1) into the solution, and synthesize the cellulose nanocrystal / polyvinyl alcohol / gelatin / sodium tetraborate decahydrate multifunctional cross-linked hydrogel through physical and chemical cross-linking under the action of a Teflon double-leaf stirrer;

[0074] (7) Centrifuge the hydrogel obtained in step (6) at a speed of 5000 r / min for 20 min to make it crosslink fully, and prepare a new type of medical dressing with high tensile strength, self-healing property, strong tissue adhesion and stable pore structure. The elongation rate of the dressing reaches more than 2000%.

[0075] As Figure 12 shown, compared with the cellulose nanofibrils used in Comparative Example 4, the hydrogel prepared from cellulose nanocrystals selected in Example 2 has high transparency (as a dressing, it can help doctors or patients observe the wound healing situation, reduce the frequency of dressing change, and effectively promote wound healing).

[0076] Example 3

[0077] Multifunctional nanofiber hydrogel medical dressing, by mass percentage, the components are: deionized water 68.25%, cellulose nanocrystals 0.75%, polyvinyl alcohol 5%, gelatin 6%, 0.1M sodium tetraborate decahydrate 20%.

[0078] A preparation method of a multifunctional nanofiber hydrogel medical dressing includes the following steps:

[0079] (1) Dissolve sodium tetraborate decahydrate in deionized water to prepare a 0.1M sodium tetraborate decahydrate solution

[0080] (2) Extract cellulose nanocrystals from cotton and linen fabrics, disperse them in deionized water, and stir magnetically at room temperature for 20 min to prepare a cellulose nanocrystal suspension with a mass fraction of 0.75%;

[0081] (3) Add polyvinyl alcohol to the cellulose nanocrystal suspension obtained in step (2), and make the volume of polyvinyl alcohol account for 5% of the cellulose nanocrystal suspension. Heat and stir at 90 °C until it is fully dissolved. The heating time is 120 min and the stirring speed is 200 r / min;

[0082] (4) Cool the solution obtained in step (3) to 60 °C while stirring, add gelatin, and make the volume of gelatin account for 6% of the cellulose nanocrystal suspension. The stirring time is 60 min and the stirring speed is 200 r / min;

[0083] (5) Cool the solution obtained in step (4) to 37 °C while stirring;

[0084] (6) Slowly drip the 0.1M sodium tetraborate decahydrate solution prepared in step (1) into the solution. The volume ratio of the sodium tetraborate decahydrate solution to the cellulose nanocrystal / polyvinyl alcohol / gelatin mixed solution is 1:5. Under the action of a polytetrafluoroethylene double-blade stirrer, a cellulose nanocrystal / polyvinyl alcohol / gelatin / sodium tetraborate decahydrate multifunctional crosslinked hydrogel is synthesized by physical and chemical crosslinking;

[0085] (7) Centrifuge the hydrogel obtained in step (6) at a speed of 5000 r / min for 20 min to make its cross-linking sufficient, and prepare a new type of medical dressing with high tensile strength, self-healing property, strong tissue adhesion and stable pore structure.

[0086] Example 4

[0087] Multifunctional nanofiber hydrogel medical dressing, by mass percentage, the components are: deionized water 68%, cellulose nanocrystals 1.0%, polyvinyl alcohol 5%, gelatin 6%, 0.1M sodium tetraborate decahydrate 20%.

[0088] A preparation method of a multifunctional nanofiber hydrogel medical dressing, comprising the following steps:

[0089] (1) Dissolve sodium tetraborate decahydrate in deionized water to prepare a 0.1M sodium tetraborate decahydrate solution

[0090] (2) Extract cellulose nanocrystals from cotton and linen fabrics, disperse them in deionized water, and magnetically stir for 20 min at room temperature to prepare a cellulose nanocrystal suspension with a concentration of 1.0%;

[0091] (3) Add polyvinyl alcohol to the cellulose nanocrystal suspension obtained in step (2), and prepare 5% of the volume of the cellulose nanocrystal suspension occupied by polyvinyl alcohol. Heat and stir at 90 °C until completely dissolved. The heating time is 120 min and the stirring speed is 200 r / min;

[0092] (4) Cool the solution obtained in step (3) to 60 °C while stirring, add gelatin, and prepare 6% of the volume of the cellulose nanocrystal suspension occupied by gelatin. The stirring time is 60 min and the stirring speed is 200 r / min;

[0093] (5) Cool the solution obtained in step (4) to 37 °C while stirring;

[0094] (6) Slowly drop the 0.1M sodium tetraborate decahydrate solution prepared in step (1) into the solution. The volume ratio of the sodium tetraborate decahydrate solution to the cellulose nanocrystal / polyvinyl alcohol / gelatin mixed solution is 1:5. Under the action of a polytetrafluoroethylene double-leaf stirrer, a cellulose nanocrystal / polyvinyl alcohol / gelatin / sodium tetraborate decahydrate multifunctional cross-linked hydrogel is synthesized through physical and chemical cross-linking;

[0095] (7) Centrifuge the hydrogel obtained in step (6) at a speed of 5000 r / min for 20 min to make its cross-linking sufficient, and prepare a new type of medical dressing with high tensile strength, self-healing property, strong tissue adhesion and stable pore structure.

[0096] Comparative Example 1

[0097] Multifunctional nanofiber hydrogel medical dressing, by mass percentage, the components are: deionized water 69%, polyvinyl alcohol 5%, gelatin 6%, 0.1M sodium tetraborate decahydrate 20%.

[0098] Preparation method of polyvinyl alcohol / gelatin / sodium tetraborate decahydrate solution adhesive hydrogel, including the following steps:

[0099] (1) Dissolve sodium tetraborate decahydrate in deionized water to prepare 0.1M sodium tetraborate decahydrate solution

[0100] (2) Dissolve polyvinyl alcohol in deionized water to prepare a 5% polyvinyl alcohol solution, and stir with a magnetic rotor while heating at 90 °C for 120 min;

[0101] (3) Cool the solution obtained in step (2) to 60 °C while stirring, add gelatin, and prepare gelatin to account for 6% of the total volume, and stir while heating for 60 min;

[0102] (4) Cool the solution obtained in step (3) to 37 °C while stirring;

[0103] (5) Slowly drop the 0.1M sodium tetraborate decahydrate solution prepared in step (1) into the solution, and the volume ratio of the sodium tetraborate decahydrate solution to the polyvinyl alcohol / gelatin mixed solution is 1:5, and physically and chemically crosslink to synthesize polyvinyl alcohol / gelatin / sodium tetraborate decahydrate hydrogel dressing.

[0104] (6) Centrifuge the hydrogel obtained in step (5) at 5000 r / min for 20 min to make the crosslinking sufficient.

[0105] Comparative Example 2

[0106] Multifunctional nanofiber hydrogel medical dressing, by mass percentage, the components are: deionized water 68.5%, cellulose nanocrystals 0.5%, polyvinyl alcohol 5%, gelatin 6%, 0.1M sodium tetraborate decahydrate 20%.

[0107] A preparation method of a multifunctional nanofiber hydrogel medical dressing, including the following steps:

[0108] (1) Dissolve sodium tetraborate decahydrate in deionized water to prepare 0.1M sodium tetraborate decahydrate solution

[0109] (2) Cellulose nanocrystals extracted from cotton and linen fabrics are dispersed in deionized water and magnetically stirred at room temperature for 20 min to prepare a 0.5% cellulose nanocrystal suspension;

[0110] (3) Add polyvinyl alcohol and gelatin to the cellulose nanocrystal suspension obtained in step (2), and prepare polyvinyl alcohol and gelatin to account for 5% and 6% of the volume of the cellulose nanocrystal suspension respectively. Heat and stir at 90 °C for 180 min with a stirring speed of 200 r / min;

[0111] (4) Cool the solution obtained in step (3) to 37 °C while stirring;

[0112] (5) Slowly drip the 0.1 M sodium tetraborate decahydrate solution prepared in step (1) into the solution. The volume ratio of the sodium tetraborate decahydrate solution to the cellulose nanocrystal / polyvinyl alcohol / gelatin mixed solution is 1:5. Under the action of a PTFE double-blade stirrer, a cellulose nanocrystal / polyvinyl alcohol / gelatin / sodium tetraborate decahydrate multifunctional cross-linked hydrogel is synthesized by physical and chemical cross-linking;

[0113] (6) Centrifuge the hydrogel obtained in step (5) at 5000 r / min for 20 min to make the cross-linking sufficient.

[0114] A large number of bubbles are generated during cross-linking, and there are still a large number of bubbles on the surface after centrifugation, resulting in poor properties such as the elongation at break, film-forming property, healing property, drug loading capacity, etc. of the dressing.

[0115] Comparative Example 3

[0116] A multifunctional nanofiber hydrogel medical dressing, by mass percentage, the components are: deionized water 68.5%, cellulose nanocrystals 0.5%, polyvinyl alcohol 5%, gelatin 6%, 0.1 M sodium tetraborate decahydrate 20%.

[0117] A preparation method of a multifunctional nanofiber hydrogel medical dressing, comprising the following steps:

[0118] (1) Dissolve sodium tetraborate decahydrate in deionized water to prepare a 0.1 M sodium tetraborate decahydrate solution

[0119] (2) Extract cellulose nanocrystals from cotton and linen fabrics, disperse them in deionized water, and magnetically stir at room temperature for 20 min to prepare a cellulose nanocrystal suspension with a mass fraction of 0.5%;

[0120] (3) Add polyvinyl alcohol and gelatin to the cellulose nanocrystal suspension obtained in step (2), and prepare polyvinyl alcohol and gelatin to account for 5% and 6% of the volume of the cellulose nanocrystal suspension respectively. Heat and stir at 60 °C for 180 min with a stirring speed of 200 r / min;

[0121] (4) Cool the solution obtained in step (3) to 37 °C while stirring;

[0122] (5) Slowly drop the 0.1 M sodium tetraborate decahydrate solution prepared in step (1) into the solution. The volume ratio of the sodium tetraborate decahydrate solution to the cellulose nanocrystal / polyvinyl alcohol / gelatin mixed solution is 1:5. Under the action of a Teflon double-leaf stirrer, a cellulose nanocrystal / polyvinyl alcohol / gelatin / sodium tetraborate decahydrate multifunctional crosslinked hydrogel is synthesized through physical and chemical crosslinking;

[0123] (6) Centrifuge the hydrogel obtained in step (5) at a speed of 5000 r / min for 20 min to make the crosslinking sufficient.

[0124] A large number of bubbles are generated during crosslinking, and there are still some bubbles on the surface after centrifugation, resulting in poor properties such as the tensile rate, film-forming property, healing property, and drug loading capacity of the dressing.

[0125] Comparative Example 4

[0126] Multifunctional nanofiber hydrogel medical dressing. By mass percentage, the components are: deionized water 68.5%, cellulose nanofibrils 0.5%, polyvinyl alcohol 5%, gelatin 6%, 0.1 M sodium tetraborate decahydrate 20%.

[0127] A preparation method of a multifunctional nanofiber hydrogel medical dressing includes the following steps:

[0128] (1) Dissolve sodium tetraborate decahydrate in deionized water to prepare a 0.1 M sodium tetraborate solution

[0129] (2) A nanofibrillated cellulose suspension (mass fraction of 1.0%), purchased from Wuhan Lana White Medical Chemical Co., Ltd. (the raw material is cotton, prepared by a mechanical method), is dispersed in deionized water and magnetically stirred at room temperature for 20 min to prepare a nanofibrillated cellulose suspension with a mass fraction of 0.5%;

[0130] (3) Add polyvinyl alcohol to the nanofibrillated cellulose suspension obtained in step (2) to make the polyvinyl alcohol account for 5% of the volume of the nanofibrillated cellulose suspension. Heat and stir at 90 °C until completely dissolved. The heating time is 120 min and the stirring speed is 200 r / min;

[0131] (4) Cool the solution obtained in step (3) to 60 °C while stirring, add gelatin to make the gelatin account for 6% of the volume of the nanofibrillated cellulose suspension, and the stirring time is 60 min and the stirring speed is 200 r / min;

[0132] (5) Cool the solution obtained in step (4) to 37 °C while stirring;

[0133] (6) Slowly drop the 0.1 M sodium tetraborate decahydrate solution prepared in step (1) into the solution, and synthesize the nanocellulose / polyvinyl alcohol / gelatin / sodium tetraborate decahydrate multifunctional crosslinked hydrogel through physical and chemical crosslinking under the action of a polytetrafluoroethylene double blade stirrer;

[0134] (7) Centrifuge the hydrogel obtained in step (6) at a speed of 5000 r / min for 20 min to make its crosslinking sufficient.

[0135] Observation of the microscopic morphology of the prepared multifunctional nanofiber hydrogel medical dressing:

[0136] As Figures 1 to 4 shown, it can be found that with the increase of cellulose nanocrystals, pore walls gradually form bridges in the middle of the pore channels, presenting a relatively tight three-dimensional network structure. Especially, the pore structures of the nanofiber hydrogels prepared in Example 2 are interlocked, and the pore structures are stable, which can effectively carry drugs. However, when the content of cellulose nanocrystals is higher than 50%, the pore walls become thicker and affect the formation of pore diameters. But as Figure 5 is the SEM image of the hydrogel without adding cellulose nanocrystals in the comparative example. It is observed from the cross-sectional and longitudinal-sectional views that there are obvious pore channels inside, and "burst release" of drugs may occur during the drug release process;

[0137] Testing the self-healing performance of the prepared multifunctional nanofiber hydrogel medical dressing:

[0138] Take samples of similar size from the comparative example and the example, divide one of them into three parts, and stain them with food-grade bright red and sky blue. It can be found that the unstained hydrogel and the stained hydrogel can be dyed with the corresponding colors just by contacting without applying external pressure, indicating that the prepared hydrogel dressing can carry out intermolecular flow inside, has strong reversible ester bonds, and promotes the self-healing property of the hydrogel dressing. With the addition of cellulose nanocrystals, the self-healing time is reduced, and it can heal quickly within 45 s. The healing times of Examples 1-4 are 35 s, 20 s, 10 s, and 5 s respectively.

[0139] Practical pictures of the structural stability, high tensile strength and tissue adhesion of the prepared multifunctional nanofiber hydrogel medical dressing:

[0140] It can be found from the physical picture that the hydrogel dressing added with cellulose nanocrystals has better structural stability and is not easily collapsed. This indicates that cellulose nanocrystals not only undergo physical and chemical reactions with polyvinyl alcohol and gelatin inside it, but also have a certain bridging effect, just like adding some straw in an adobe house to achieve the effects of firmness, durability, moisture retention and heat insulation, giving a certain sense of cool comfort to the skin tissue. The elongation rate reaches more than 2000% (Examples 2 and 3) and it has strong adhesion to the skin tissue. The amount of the dressing used can be selected according to the size of the wound, meeting the requirement of "what is taken is what is needed".

[0141] Analysis of the antibacterial effect of the prepared multifunctional nanofiber hydrogel medical dressing on Staphylococcus aureus:

[0142] The prepared nanofiber hydrogel has a certain antibacterial effect and can be used as a substrate material for antibacterial hemostasis and repair, becoming a new type of medical dressing.

Claims

1. A nanofiber hydrogel, characterized in that, By mass percentage, the components include: 47% - 86.9% of water, 0.1% - 1.0% of cellulose nanocrystals, 1% - 10% of polymer, 2% - 12% of protein, and 10% - 30% of crosslinking agent; the polymer is polyvinyl alcohol; the protein is one or more of gelatin or gelatin derivatives; the crosslinking agent is sodium tetraborate; The preparation method of the nanofiber hydrogel includes: (1) Mix the suspension of the polymer and cellulose nanocrystals, heat in a water bath, stir and dissolve to obtain a first solution, and the water bath heating temperature is 85°C - 95°C; (2) Add the protein to the first solution obtained in step (1), heat in a water bath, stir and dissolve to obtain a second solution, and the water bath heating temperature is 55°C - 65°C; (3) Mix the second solution obtained in step (2) with the crosslinking agent, crosslink, and then centrifuge to defoam to obtain the nanofiber hydrogel.

2. The hydrogel according to claim 1, characterized in that, The cellulose nanocrystals are extracted from cotton and linen plants.

3. The hydrogel according to claim 1, wherein The degree of alcoholysis of the polyvinyl alcohol is above 78%.

4. The preparation method of the nanofiber hydrogel according to any one of claims 1 - 3, including: (1) Mix the suspension of the polymer and cellulose nanocrystals, heat in a water bath, stir and dissolve to obtain a first solution, and the water bath heating temperature is 85°C - 95°C; (2) Add the protein to the first solution obtained in step (1), heat in a water bath, stir and dissolve to obtain a second solution, and the water bath heating temperature is 55°C - 65°C; (3) Mix the second solution obtained in step (2) with the crosslinking agent, crosslink, and then centrifuge to defoam to obtain the nanofiber hydrogel.

5. The preparation method according to claim 4, characterized in that, In step (1), the cellulose nanocrystals use cotton and linen plants as raw materials, and natural cellulose nanocrystals are extracted by an acid method combined with high-pressure homogenization; Wherein the mass fraction of the acid in the acid method is 10% - 70%, the acid hydrolysis temperature is 35°C - 85°C, and the acid hydrolysis time is 20 min - 60 min; the high-pressure homogenization is cycled 5 - 15 times, the inlet air pressure gauge during homogenization is below 0.7 MPa, and the maximum pressure value is below 100 MPa; the acid is one or more of inorganic acids and organic acids; the inorganic acid is one or more of sulfuric acid, hydrochloric acid, and phosphoric acid; the organic acid is one or more of oxalic acid, maleic acid, and toluic acid.

6. The preparation method according to claim 4, wherein In step (1), the mass fraction of the cellulose nanocrystal suspension is 0.1% - 1.0%; in step (1), the heating time is 60 min - 180 min, and the stirring speed is 100 r / min - 500 r / min.

7. According to the preparation method described in claim 4, characterized in that, In step (2), the heating time is 30 min - 90 min, and the stirring speed is 100 r / min - 500 r / min.

8. The preparation method according to claim 4, characterized in that, In step (3), the crosslinking temperature is 35°C - 39°C, the centrifugation speed is 5000 r / min, and the centrifugation time is 10 min - 40 min.

9. A drug-loaded hydrogel, characterized in that, The drug-loaded hydrogel uses the nanofiber hydrogel according to any one of claims 1 - 3 as a carrier to load drugs.

10. The application of the nanofiber hydrogel according to any one of claims 1 - 3 in medical dressings.

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