A nanofiber wound dressing formed by spraying at short distances and a method of making

Abstract

The application discloses a kind of nanofiber wound dressings formed by spraying under short distance and preparation method, comprising the following steps: S1, preparation of polymer solution: PLGA polymer, PLLA polymer and solvent are mixed uniformly to obtain polymer solution, wherein the mass ratio of PLGA polymer, PLLA polymer and solvent is 4-8:1-3:89-95, different spraying distance corresponds to different mass ratio;S2, print fiber in situ: the polymer solution prepared in step S1 is printed fiber using solution spinning, wherein the spraying distance is less than or equal to 10 cm, the spraying air pressure is 125-200kpa, different spraying distance corresponds to different spraying air pressure.The application not only can realize the formation of nanofiber wound dressings by spraying under short distance, and the prepared nanofiber wound dressings have excellent mechanical strength and good adhesion.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of nanofiber preparation, and particularly relates to a nanofiber wound dressing formed by spraying at a short distance and a preparation method. BACKGROUND

[0002] Traditional wound dressings are basically gauze composed of cotton, rayon, polyester and non-woven fabric, which are used to prevent bacterial infection. Although they have the advantages of cost-effectiveness and ease of use, they are easily contaminated by the outside world, have poor bacterial protection, and therefore need to be replaced frequently to protect healthy tissues from damage, but at the same time will promote rapid dehydration of the wound, cause removal pain, and have very many limitations in use, and they passively act on the wound healing process and cannot accelerate the healing of the wound environment.

[0003] Nanofiber dressings have good porosity, allowing effective penetration of water and oxygen, superior exchange of nutrients and removal of metabolic waste, which can effectively promote wound healing. In addition, nanoscale fibers endow the dressing with small gaps and high surface area, which can enhance hemostasis. The small pore size of the nanofiber dressing not only protects the wound from bacterial infection and cell / tissue ingrowth, but also is more advantageous than microfiber and mesh commercial counterparts, and the nanofiber dressing can provide excellent compliance, thereby better covering and protecting the wound from infection. Most importantly, the broad surface area of the nanofiber dressing can effectively load / incorporate drugs compared to commercial dressings. Therefore, they show promising potential for developing advanced bioactive dressings.

[0004] Traditional cotton gauze is increasingly being replaced by new high-end medical dressings; some new high-end medical dressings with stronger functionality can not only make the wound heal better, but also save nursing costs for patients, and greatly reduce nursing time and consumption of various auxiliary materials used in the nursing process. With the frequent outbreak of epidemic infectious diseases worldwide, the world population is aging, developed countries and regions have an urgent need to improve medical standards, and people's awareness of health care is increasing, and there is still a large gap in meeting the demand for global medical dressing market. It can be expected that for a considerable period of time in the future, the medical dressing industry will maintain sustained growth.

[0005] Nowadays, the technology for preparing nanofibers has also been relatively mature, such as electrospinning (ES), centrifugal spinning, self-assembly technology, template synthesis, melt-blow spinning and solution blowing spinning (SBS), etc. Although it has developed into a mature technology for preparing nanofibers and has been widely used in various fields, it still has a series of problems. For example, electrospinning requires the use of high-voltage electricity, the collector generally needs certain conductivity, and the conductivity of the spinning material or the spinning solution system cannot be too good, which also limits the preparation of conductive polymer fibers. Solution blowing spinning technology has a faster spinning rate (several times or even dozens of times) than electrospinning, does not require a high-voltage working environment, and is easy to realize multi-nozzle spinning, so it is more secure and has the condition of rapid deposition of fibers.

[0006] Although there are many studies on nanofiber dressings at present, there are still some problems. First, although there are many types of nanofiber wound dressings on the market, there are generally problems of low mechanical strength and weak adhesion. Second, the principle of fiber generation is based on the Bernoulli principle, under the action of high-speed airflow, the organic solvent in the polymer solution volatilizes quickly, thereby generating nanofibers with good fiber morphology. Based on this, the organic solvent needs to be volatilized when generating fibers, and increasing the spraying distance is an effective method for the solvent to volatilize fully, so the spraying distance when many studies generate fiber membranes is about 15 cm or more, which has a greater demand for the operation space of fiber generation, which is not conducive to the in-situ generation of nanofibers. SUMMARY

[0007] The purpose of the present application is to provide a nanofiber wound dressing formed by spraying at a short distance and a preparation method, which can not only form a nanofiber wound dressing by spraying at a short distance, but also has excellent mechanical strength and good adhesion.

[0008] The present application is realized by the following technical solutions:

[0009] A preparation method of a nanofiber wound dressing, comprising the following steps:

[0010] S1, preparing a polymer solution: uniformly mixing PLGA polymer, PLLA polymer and solvent to obtain a polymer solution, wherein the mass ratio of the PLGA polymer, the PLLA polymer and the solvent is 4-8:1-3:89-95, and different spraying distances correspond to different mass ratios;

[0011] S2, printing fibers in-situ: printing fibers by using a solution spinning technology for the polymer solution prepared in step S1, wherein the spraying distance is less than or equal to 10 cm, and the spraying air pressure is 125-200 kpa, and different spraying distances correspond to different spraying air pressures.

[0012] In situ printing is a bio-printing technology that can directly print biomaterials at the original location of tissues or organs. This technology is particularly important in tissue engineering and regenerative medicine, as it can accurately repair damaged tissues without damaging surrounding healthy tissues. In situ printing refers to a manufacturing method that prints at the original location of an object. The solution spinning technology described in this paper can achieve in situ printing, that is, directly producing nanofiber dressings on wounds without the need for additional transplantation.

[0013] Solution spinning printing fibers is a prior art, and fiber printing is carried out using this method. In this process, there are many factors that affect the morphology of the generated fibers, such as spraying air pressure, spraying distance, concentration of polymer components, rate of solution propulsion, speed of nozzle movement, etc. The applicant has found through research and experiments that:

[0014] Spraying air pressure, spraying distance, and concentration of polymer components are the main factors affecting fiber morphology. Good fiber morphology can promote cell proliferation on the fiber, thereby accelerating wound healing. Therefore, by reasonably controlling the spraying air pressure, spraying distance, and concentration of polymer components, good fiber morphology can be prepared.

[0015] In the prior art, in order to volatilize the organic solvent, the spraying distance is usually increased to about 15 cm or more. This requires a larger operation space for fiber generation, which is not conducive to in situ production of nanofibers.

[0016] The original intention of the present application is to overcome the conventional thinking that only long-distance (greater than or equal to 15 cm) spraying printing fibers can be achieved, and to develop a short-distance (less than or equal to 10 cm) spraying printing fiber process to achieve in situ production of nanofibers and reduce the requirement for operation space.

[0017] Therefore, based on the discovery that spraying air pressure, spraying distance, and concentration of polymer components are the main factors affecting fiber morphology, the present application reasonably designs the relationship between spraying air pressure, spraying distance, and concentration of polymer components through experiments to find effective conditions for forming good nanofibers at short distances.

[0018] Firstly, the present application improves the polymer solution by using a combination of PLGA polymer, PLLA polymer, and solvent. PLGA (poly(lactic-co-glycolic acid)) is a commonly used biocompatible material on the market that can produce fibers. However, the mechanical strength of nanofibers formed by single-component PLGA is low. By forming a composite material with PLLA (poly-L-lactic acid), the overall mechanical strength of the fiber membrane (nanofiber wound dressing) can be improved.

[0019] Secondly, based on the designed polymer solution, the relationship between the spraying air pressure, the spraying distance, and the concentration of the polymer component is reasonably designed, when the spraying distance is less than or equal to 10 cm, the spraying air pressure is 125-200 kpa, and the mass ratio of the PLGA polymer, the PLLA polymer and the solvent is 4-8:1-3:89-95.

[0020] In conclusion, the present application can not only realize the spraying of the nanofiber wound dressing at a short distance, but also the prepared nanofiber wound dressing has excellent mechanical strength and good adhesion.

[0021] Further, the viscosity of the PLGA polymer is 0.4-0.6 dL / g, and the molecular weight is 5-7 W; the viscosity of the PLLA polymer is 2.5-3.0 dL / g, and the molecular weight is 36-48 W.

[0022] Further, the solvent includes dichloromethane solution.

[0023] Further, in the step S1, the mixing is performed by ultrasonic mixing.

[0024] Further, in the step S2, the spraying is performed for at least one layer.

[0025] A nanofiber wound dressing formed by spraying at a short distance, wherein the nanofiber wound dressing is prepared by the above preparation method.

[0026] Further, the nanofiber wound dressing is printed at a spraying distance of 10 cm; wherein the spraying air pressure is 190-200 kpa; and the mass ratio of the PLGA polymer, the PLLA polymer and the solvent is 7-8:2-3:89-91.

[0027] Further, the nanofiber wound dressing is printed at a spraying distance of 5 cm; wherein the spraying air pressure is 170-180 kpa; and the mass ratio of the PLGA polymer, the PLLA polymer and the solvent is 6-7:1-2:91-93.

[0028] Further, the nanofiber wound dressing is printed at a spraying distance of 2 cm; wherein the spraying air pressure is 125-135 kpa; and the mass ratio of the PLGA polymer, the PLLA polymer and the solvent is 3-4:1-2:94-96.

[0029] Further, the spraying layer number of the nanofiber wound dressing is 3-5 layers.

[0030] Compared with the prior art, the present application has the following advantages and beneficial effects:

[0031] The present application aims at the problems of large operation distance and space required when fibers are produced by conventional solution spinning method, and low mechanical strength and poor adhesion of common fiber membranes, etc., by improving the polymer solution, and reasonably designing the relationship among the spraying air pressure, spraying distance, and concentration of polymer components based on the designed polymer solution, the nanofiber wound dressing can be formed by spraying at a short distance, and the prepared nanofiber wound dressing has excellent mechanical strength and good adhesion. BRIEF DESCRIPTION OF DRAWINGS

[0032] The drawings described herein are used to provide further understanding of the embodiments of the present application, form a part of the present application, and do not constitute a limitation on the embodiments of the present application. In the drawings:

[0033] Figure 1 SEM images of the fibers formed at a short distance (10 cm, 5 cm, 2 cm) in the present application, wherein (a), (b) and (c) represent the fibers formed at 2 cm, 5 cm and 10 cm, respectively;

[0034] Figure 2 Diameter distribution diagram of the fibers formed at a short distance (10 cm, 5 cm, 2 cm) in the present application, wherein (a), (b) and (c) represent the diameter distribution of the fibers formed at 2 cm, 5 cm and 10 cm, respectively;

[0035] Figure 3 Mechanical property diagram of the fibers formed at a short distance (10 cm, 5 cm, 2 cm) in the present application, wherein (a) is the stress-strain image of the nanofiber membranes with the same number of layers at different distances; (b) is the breaking strain and breaking elongation of the nanofiber membranes with the same number of layers at different distances; (c) is the Young's modulus of each fiber membrane; (d) is the stress-strain image of the fiber membranes with different numbers of layers at the same distance; (e) is the breaking strain and breaking elongation of the fiber membranes with different numbers of layers at the same distance; (f) is the tensile process of the fiber membranes;

[0036] Figure 4 Adhesion property diagram of the fibers formed at a short distance (10 cm, 5 cm, 2 cm) in the present application, wherein (a) is the fitting curve of the peeling force of the fiber membranes and ordinary adhesive plaster; (b) is the peeling energy of the fiber membranes and ordinary adhesive plaster; (c) is the photo of the 180° peeling test device for measuring the interfacial toughness;

[0037] Figure 5 Hydrophilicity diagram of the fibers formed at a short distance (10 cm, 5 cm, 2 cm) in the present application, wherein (a) is a schematic diagram of contact angle measurement; (b) is the contact angle of each fiber membrane;

[0038] Figure 6A chart for water vapor permeability, water retention, water absorption and degradation performance of the fiber film (10 cm-3c) of the present application, wherein (a), (b), (c) and (d) are water vapor permeability, water retention, water absorption and degradation performance, respectively.

[0039] Figure 7 An image comparison of fibers prepared in Example 1, Comparative Examples 1-8 under optical microscope observation, wherein (a) is a fiber image of Comparative Example 1; (b) is a fiber image of Comparative Example 2; (c) is a fiber image of Comparative Example 3; (d) is a fiber image of Comparative Example 4; (e) is a fiber image of Comparative Example 5; (f) is a fiber image of Example 1; (g) is a fiber image of Comparative Example 6; (h) is a fiber image of Comparative Example 7; (i) is a fiber image of Comparative Example 8.

[0040] Figure 8 An image comparison of fibers prepared in Example 2, Comparative Examples 9-16 under optical microscope observation, wherein (a) is a fiber image of Comparative Example 9; (b) is a fiber image of Comparative Example 10; (c) is a fiber image of Comparative Example 11; (d) is a fiber image of Example 2; (e) is a fiber image of Comparative Example 12; (f) is a fiber image of Comparative Example 13; (g) is a fiber image of Comparative Example 14; (h) is a fiber image of Comparative Example 15; (i) is a fiber image of Comparative Example 16.

[0041] Figure 9 An image comparison of fibers prepared in Example 3, Comparative Examples 17-24 under optical microscope observation, wherein (a) is a fiber image of Comparative Example 17; (b) is a fiber image of Example 3; (c) is a fiber image of Comparative Example 18; (d) is a fiber image of Comparative Example 18; (e) is a fiber image of Comparative Example 20; (f) is a fiber image of Comparative Example 21; (g) is a fiber image of Comparative Example 22; (h) is a fiber image of Comparative Example 23; (i) is a fiber image of Comparative Example 24. DETAILED DESCRIPTION

[0042] In order to make the purpose, technical scheme and advantages of the present application clearer, further detailed description will be given below in combination with examples and drawings, and the schematic embodiments of the present application and their description are only used to explain the present application, and do not limit the present application.

[0043] Example:

[0044] A preparation method of a nanofiber wound dressing, comprising the following steps:

[0045] S1, preparing a polymer solution: uniformly mixing PLGA polymer, PLLA polymer and solvent to obtain a polymer solution, and the mixing mode is ultrasonic mixing, wherein the mass ratio of PLGA polymer, PLLA polymer and solvent is 4-8:1-3:89-95, and different spraying distances correspond to different mass ratios.

[0046] The spraying distance is equal to 10 cm, the spraying air pressure is 190-200 kpa, the mass ratio of the PLGA polymer, the PLLA polymer and the solvent is 7-8:2-3:89-91.

[0047] The spraying distance is equal to 5 cm, the spraying air pressure is 170-180 kpa, the volume ratio of the PLGA polymer, the PLLA polymer and the solvent is the mass ratio of 6-7:1-2:91-93.

[0048] The spraying distance is equal to 2 cm, the spraying air pressure is 125-135 kpa, the volume ratio of the PLGA polymer, the PLLA polymer and the solvent is the mass ratio of 3-4:1-2:94-96.

[0049] The viscosity of the PLGA polymer is 0.4-0.6 dL / g, and the molecular weight is 5-7 W; the viscosity of the PLLA polymer is 2.5-3.0 dL / g, and the molecular weight is 36-48 W; the solvent includes dichloromethane solution and other organic solvents.

[0050] S2, printing fibers in situ: using solution spinning printing technology to print fibers from the polymer solution prepared in step S1, wherein the spraying distance is less than or equal to 10 cm, the spraying air pressure is 105-200 kpa, different spraying distances correspond to different spraying air pressures, and the number of spraying layers is at least one.

[0051] The equipment for printing fibers in situ is an in-situ biological printer integrated by a gas pressure adjusting system, a solution propelling system, a nozzle, a printing platform and a control system. The gas pressure adjusting system is composed of a gas pump and a gas pressure regulator, which can accurately control the gas pressure; the solution propelling system is driven by a motor to drive a lead screw to push a needle cylinder containing a solvent, thereby controlling the solution propelling rate; the nozzle adopts a coaxial nozzle, so that the gas and the polymer solution can flow out, and the solution can volatilize under the shearing force of the pressurized gas, thereby generating fibers; the printing platform is used for the nozzle to move in the xy direction, and the collector can move in the z-axis direction; the control system can be linked with other parts to comprehensively control the printing of the fibers.

[0052] The embodiment can not only realize the spraying of nanofiber wound dressings at a short distance, but also prepare nanofiber wound dressings with excellent mechanical strength and good adhesion by improving the polymer solution and reasonably designing the relationship among the spraying air pressure, the spraying distance and the concentration of the polymer components based on the designed polymer solution.

[0053] Example 1:

[0054] A nanofiber wound dressing formed by spraying at a short distance, wherein the nanofiber wound dressing is printed at a spraying distance of 10 cm; wherein the spraying air pressure is 200 kpa; the volume ratio of the PLGA polymer, the PLLA polymer and the solvent is 8:3:89.

[0055] The viscosity of the PLGA polymer is 0.46 dL / g, and the molecular weight is 5.5 W; the viscosity of the PLLA polymer is 2.5 dL / g, and the molecular weight is 36 W; the solvent is dichloromethane solution.

[0056] In the specific experiment, the polymer solution used to generate fibers at 10 cm: 500 mg of PLGA polymer and 187.5 mg of PLLA were weighed at room temperature and placed in the same test tube, 4.198 mL of dichloromethane solvent was added to the test tube, the test tube was sealed and placed in an ultrasonic machine for 3 h to obtain a uniformly mixed polymer solution.

[0057] Comparative Example 1:

[0058] This comparative example is based on Example 1, and the difference from Example 1 is that the volume ratio of the PLGA polymer, the PLLA polymer and the solvent is 6:1:93 (the component ratio is different from Example 1), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the condition of Example 1, the generated fibers are clearer, more evenly distributed, and less entangled.

[0059] Comparative Example 2:

[0060] This comparative example is based on Example 1, and the difference from Example 1 is that the spraying air pressure is 230 kpa (higher than Example 1), and the volume ratio of the PLGA polymer, the PLLA polymer and the solvent is 6:2:92 (the component ratio is different from Example 1), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the condition of Example 1, the generated fibers are clearer, more evenly distributed, and less entangled.

[0061] Comparative Example 3:

[0062] This comparative example is based on Example 1, and the difference from Example 1 is that the spraying air pressure is 260 kpa (higher than Example 1), and the volume ratio of the PLGA polymer, the PLLA polymer and the solvent is 6:3:91 (the component ratio is different from Example 1), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the condition of Example 1, the generated fibers are clearer, more evenly distributed, and less entangled.

[0063] Comparative Example 4:

[0064] The comparative example is based on example 1, and the difference from example 1 is that the spraying air pressure is 230 kpa (higher than example 1), the volume ratio of PLGA polymer, PLLA polymer and solvent is 8:1:91 (the component ratio is different from example 1), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the conditions of example 1, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0065] Comparative example 5:

[0066] The comparative example is based on example 1, and the difference from example 1 is that the spraying air pressure is 260 kpa (higher than example 1), the volume ratio of PLGA polymer, PLLA polymer and solvent is 8:2:90 (the component ratio is different from example 1), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the conditions of example 1, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0067] Comparative example 6:

[0068] The comparative example is based on example 1, and the difference from example 1 is that the spraying air pressure is 260 kpa (higher than example 1), the volume ratio of PLGA polymer, PLLA polymer and solvent is 10:1:89 (the component ratio is different from example 1), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the conditions of example 1, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0069] Comparative example 7:

[0070] The comparative example is based on example 1, and the difference from example 1 is that the volume ratio of PLGA polymer, PLLA polymer and solvent is 10:2:88 (the component ratio is different from example 1), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the conditions of example 1, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0071] Comparative example 8:

[0072] The comparative example is based on example 1, and the difference from example 1 is that the spraying air pressure is 230 kpa (higher than example 1), the volume ratio of PLGA polymer, PLLA polymer and solvent is 10:3:87 (the component ratio is different from example 1), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the conditions of example 1, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0073] The parameters of example 1, comparative example 1 to comparative example 8 are shown in table 1:

[0074] Table 1

[0075]

[0076] The images of the fibers prepared in Example 1, Comparative Example 1- Comparative Example 8 under optical microscope observation are compared as shown in the following table: Figure 7

[0077] From the images, it can be seen that the fiber of Example 1, i.e. Figure (f) exhibits less bubbles and clearer fiber morphology.

[0078] Example 2:

[0079] A nanofiber wound dressing formed by spraying at a short distance, the nanofiber wound dressing is printed at a spraying distance equal to 5 cm; wherein the spraying air pressure is 180 kpa; the volume ratio of the PLGA polymer, the PLLA polymer and the solvent is 7:1:92.

[0080] The viscosity of the PLGA polymer is 0.46 dL / g, and the molecular weight is 5.5 W; the viscosity of the PLLA polymer is 2.5 dL / g, and the molecular weight is 36 W; the solvent is dichloromethane solution.

[0081] In the specific experiment, 500 mg of PLGA polymer and 71 mg of PLLA were weighed at room temperature and placed in the same test tube, 4.960 mL of dichloromethane solvent was added to the test tube, the test tube was sealed and placed in an ultrasonic machine for 3 h to obtain a uniformly mixed polymer solution.

[0082] Comparative Example 9:

[0083] This comparative example is based on Example 2, and the difference from Example 2 is that the spraying air pressure is 160 kpa (lower than Example 2), the volume ratio of the PLGA polymer, the PLLA polymer and the solvent is 5:1:94 (the component ratio is different from Example 2), and the sprayed fibers are imaged under an optical microscope. It is found that under the conditions of Example 2, the produced fibers are more evenly distributed, and the fiber entanglement is less.

[0084] Comparative Example 10:

[0085] This comparative example is based on Example 2, and the difference from Example 2 is that the volume ratio of the PLGA polymer, the PLLA polymer and the solvent is 5:2:93 (the component ratio is different from Example 2), and the sprayed fibers are imaged under an optical microscope. It is found that under the conditions of Example 2, the produced fibers are clearer, more evenly distributed, and less entangled.

[0086] Comparative Example 11: ​

[0087] The comparative example is based on Example 2, and the difference between Example 2 is that the spraying air pressure is 200kpa (higher than Example 2), the volume ratio of PLGA polymer, PLLA polymer and solvent is 5:3:92 (the component ratio is different from Example 2), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the condition of Example 2, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0088] Comparative Example 12:

[0089] The comparative example is based on Example 2, and the difference between Example 2 is that the spraying air pressure is 200kpa (higher than Example 2), the volume ratio of PLGA polymer, PLLA polymer and solvent is 7:2:91 (the component ratio is different from Example 2), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the condition of Example 2, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0090] Comparative Example 13:

[0091] The comparative example is based on Example 2, and the difference between Example 2 is that the spraying air pressure is 160kpa (lower than Example 2), the volume ratio of PLGA polymer, PLLA polymer and solvent is 7:3:90 (the component ratio is different from Example 2), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the condition of Example 2, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0092] Comparative Example 14:

[0093] The comparative example is based on Example 2, and the difference between Example 2 is that the spraying air pressure is 200kpa (higher than Example 2), the volume ratio of PLGA polymer, PLLA polymer and solvent is 9:1:90 (the component ratio is different from Example 2), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the condition of Example 2, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0094] Comparative Example 15:

[0095] The comparative example is based on Example 1, and the difference between Example 1 is that the spraying air pressure is 160kpa (lower than Example 2), the volume ratio of PLGA polymer, PLLA polymer and solvent is 9:2:89 (the component ratio is different from Example 2), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the condition of Example 2, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0096] Comparative Example 16:

[0097] The comparative example is based on Example 2, and the difference from Example 2 is that the volume ratio of the PLGA polymer, the PLLA polymer and the solvent is 9:3:88 (the component ratio is different from Example 2), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the condition of Example 2, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0098] The parameters of Example 2, Comparative Example 9-Comparative Example 16 are shown in Table 2:

[0099] Table 2

[0100]

[0101] The images of the fibers prepared in Example 2, Comparative Example 9-Comparative Example 16 observed under an optical microscope are compared as shown in Figure 8 .

[0102] As can be seen from the figure, Figure (d) i.e. the fibers of Example 2 exhibit fewer bubbles and clearer fiber morphology.

[0103] Example 3:

[0104] A nanofiber wound dressing formed by spraying at a short distance, which is printed at a spraying distance equal to 2 cm; wherein the spraying air pressure is 125 kpa; the volume ratio of the PLGA polymer, the PLLA polymer and the solvent is 4:2:94.

[0105] The viscosity of the PLGA polymer is 0.46 dL / g, and the molecular weight is 5.5 W; the viscosity of the PLLA polymer is 2.5 dL / g, and the molecular weight is 36 w; the solvent is dichloromethane solution.

[0106] In the specific experiment, 500 mg of PLGA polymer and 250 mg of PLLA were weighed at room temperature, and placed in the same test tube, 8.868 mL of dichloromethane solvent was added to the test tube, the test tube was sealed, and placed in an ultrasonic machine for 3 h to obtain a uniformly mixed polymer solution.

[0107] Comparative Example 17:

[0108] The comparative example is based on Example 3, and the difference from Example 3 is that the spraying air pressure is 100 kpa (lower than Example 3), the volume ratio of the PLGA polymer, the PLLA polymer and the solvent is 4:1:95 (the component ratio is different from Example 3), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the condition of Example 3, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0109] Comparative Example 18:

[0110] This comparative example is based on Example 3, with the difference from Example 3 being that the spraying air pressure is 150 kpa (higher than Example 3), the volume ratio of PLGA polymer, PLLA polymer and solvent is 5:2:93 (different from the component ratio of Example 3), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the conditions of Example 3, the generated fibers are clearer, more evenly distributed, and less entangled.

[0111] Comparative Example 19:

[0112] This comparative example is based on Example 3, with the difference from Example 3 being that the volume ratio of PLGA polymer, PLLA polymer and solvent is 5:1:95 (different from the component ratio of Example 3), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the conditions of Example 3, the generated fibers are clearer, more evenly distributed, and less entangled.

[0113] Comparative Example 20:

[0114] This comparative example is based on Example 3, with the difference from Example 3 being that the spraying air pressure is 150 kpa (higher than Example 3), the volume ratio of PLGA polymer, PLLA polymer and solvent is 5:2:93 (different from the component ratio of Example 3), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the conditions of Example 3, the generated fibers are clearer, more evenly distributed, and less entangled.

[0115] Comparative Example 21:

[0116] This comparative example is based on Example 3, with the difference from Example 3 being that the spraying air pressure is 100 kpa (lower than Example 3), the volume ratio of PLGA polymer, PLLA polymer and solvent is 5:3:92 (different from the component ratio of Example 3), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the conditions of Example 3, the generated fibers are clearer, more evenly distributed, and less entangled.

[0117] Comparative Example 22:

[0118] This comparative example is based on Example 3, with the difference from Example 3 being that the spraying air pressure is 150 kpa (higher than Example 3), the volume ratio of PLGA polymer, PLLA polymer and solvent is 6:1:93 (different from the component ratio of Example 3), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the conditions of Example 3, the generated fibers are clearer, more evenly distributed, and less entangled.

[0119] Comparative Example 23:

[0120] This comparative example is based on Example 3, with the difference from Example 3 being that the spraying air pressure is 100 kpa (lower than Example 3), the volume ratio of PLGA polymer, PLLA polymer and solvent is 6:2:98 (the component ratio is different from Example 3), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the conditions of Example 3, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0121] Comparative Example 24:

[0122] This comparative example is based on Example 3, with the difference from Example 3 being that the volume ratio of PLGA polymer, PLLA polymer and solvent is 6:3:91 (the component ratio is different from Example 3), and the sprayed fibers are imaged under an optical microscope. It is found by comparison that under the conditions of Example 3, the generated fibers are clearer, more uniform in distribution, and less entangled.

[0123] Example 3, Comparative Example 17-Comparative Example 24 Parameter Comparison Table 3:

[0124] Table 3

[0125]

[0126] Example 3, Comparative Example 17-Comparative Example 24 prepared fiber images observed under an optical microscope are shown in Figure 9

[0127] As can be seen from the figure, Figure (b) i.e. Example 3 fiber exhibits fewer bubbles and clearer fiber morphology.

[0128] The following effect verification was performed on the fiber membranes prepared at different short distances:

[0129] (1) Forming fibers at short distances

[0130] SEM electron scanning (SEM) of the generated fiber membranes can be seen that fibers of good morphology are generated at three distances. The fiber diameter was analyzed and counted using image plug-in and oringe software Figure 1 Figure 2 ​​), 2 cm distance, the diameter of the nanofiber produced by the in-situ bio-printer is mainly distributed between 100-150 nm; 5 cm, the fiber diameter is mainly distributed between 150-200 nm; 10 cm, the fiber diameter is mainly distributed between 400-500 nm, the fiber diameter increases with the increase of distance. At the same time, there are holes on the surface of the fiber, which may be due to the use of solution spinning method to produce fiber from polymer solvent, the rapid phase separation produces irregular phase morphology, the solvent in the solvent-rich region evaporates rapidly to form pores, which increases the specific surface area of the fiber, and can effectively improve the adhesion of drugs and cells.

[0131] (2) Mechanical properties of fiber membrane

[0132] The mechanical properties of fiber membranes sprayed at different distances and different layers were explored. Figure 3 ) The results showed that at 10 cm, 5 cm, and 2 cm distances, the fiber membranes sprayed at the same number of layers, the breaking stress of the fiber membrane increased with the increase of spraying distance, the breaking elongation decreased with the increase of distance, and the Young's modulus increased with the increase of spraying distance. At the same distance of 10 cm, 3 layers, 4 layers, and 5 layers of fiber membranes were sprayed respectively, the breaking stress of the fiber membrane increased with the increase of the number of sprayed layers, the breaking elongation decreased with the increase of the number of sprayed layers, and the Young's modulus increased with the increase of the number of sprayed layers. Combined with the SEM image analysis of the fiber, there are holes on the surface of the fiber, and the single fiber sprayed at high distance is more closely connected and has higher strength; the single fiber sprayed at short distance is relatively not particularly closely connected under the action of the hole, but has stronger deformation ability; therefore, the fiber membrane sprayed at high distance has higher strength and lower deformation ability compared with the fiber membrane sprayed at short distance. The Young's modulus of the 10 cm-3c fiber membrane is in the range of 20-40 Mpa, which is consistent with the Young's modulus range of human skin surface, and the breaking stress is about 3.5 Mpa, and the breaking elongation is close to 175%, which has good mechanical strength. When the fiber membrane is applied to the skin, it can move with the skin and also protect the skin from external pollution and damage.

[0133] (3) Adhesion of fiber membrane

[0134] The adhesion of fiber membranes sprayed at different distances and the same number of layers to the skin was explored. Figure 4 ) The experimental data showed that the adhesion of 10 cm-3c fiber membrane, 5 cm-3c fiber membrane, and 2 cm-3c fiber membrane to the skin was similar to that of adhesive plaster, which could meet the daily needs of wound dressing adhesion to the wound. The fiber membrane is deposited on the rough surface of the wound, which can be entangled and adhered to the wound tissue on one hand, and can absorb the exudate of the wound on the other hand, and can preserve the wound healing.

[0135] (4) Analysis of the hydrophilic property of the fiber membrane

[0136] Water contact angle is an important indicator for evaluating the hydrophilic property of the wound dressing. Good hydrophilic property of the fiber membrane can promote its adhesion and cell growth, so the contact angle analysis was also performed on each fiber membrane (see Table 3 below), and it was found that the contact angle of the fiber membrane formed under various conditions was between 60-80°, which was less than 90°, indicating that the fiber membrane had good hydrophilic property, which could promote cell adhesion and proliferation during the wound healing process. Figure 5

[0137] (5) Analysis of the water vapor transmission rate, water retention, water absorption and degradation property of the fiber membrane

[0138] Water vapor transmission rate (WVTR) is an important characteristic of the wound dressing, which can create a suitable microenvironment for wound healing. High WVTR of the wound dressing makes the wound exudate easy to evaporate, which cannot maintain the moist environment on the surface of the wound that hinders wound healing. On the contrary, low WVTR is not conducive to the gas-liquid exchange of tissue cells, which slows down the proliferation of fibroblasts and the growth of granulation tissue. Therefore, we checked the WVTR of the nanofiber membrane (see Table 4 below). The water vapor transmission rates of the control group without covering the nanofiber membrane and the 10 cm-3c PLGA / PLLA nanofiber membrane group were 0.2972±0.0027 g / (cm2·24h) and 0.1979±0.0097 g / (cm2·24h), respectively, wherein the water vapor transmission rate of the PLLA / PLGA nanofiber membrane group was less than that of the control group, which could prevent the evaporation of a certain amount of water at the wound site and maintain a suitable moist environment. The water retention, water absorption and degradation of the fiber membrane were also analyzed. After 6h of exposure in air, the water retention of the fiber membrane remained at about 40%, and after 10h, the water was basically lost. Moreover, the water absorption rate of the fiber membrane also increased within a certain range with time, and after 10h, the water absorption rate could reach 20% of its own weight. In addition, the PLGA / PLLA degraded about 15% within 3 weeks, and the degradation rate increased with time. Figure 6

[0139] In summary, the present application provides an experimental condition for forming a PLGA / PLLA composite nanofiber membrane at a short distance (10 cm, 5 cm, 2 cm), and based on this condition, a biocompatible composite nanofiber membrane with excellent mechanical strength and good adhesion is prepared.

[0140] ​​The above detailed description of the specific embodiments of the present application has been given to understand the purpose, technical solutions and beneficial effects of the present application. It should be understood that the above description is only a specific embodiment of the present application and is not used to limit the protection scope of the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A method for preparing a nanofiber wound dressing, characterized in that, Includes the following steps: S1. Preparation of polymer solution: Mix PLGA polymer, PLLA polymer and solvent evenly to obtain polymer solution; PLGA polymer has a viscosity of 0.46 dL / g and a molecular weight of 5.5 W; PLLA polymer has a viscosity of 2.5 dL / g and a molecular weight of 36 W; the solvent is dichloromethane; S2, In-situ fiber printing: The polymer solution prepared in step S1 is used to print fibers using solution spinning technology; This nanofiber wound dressing was printed at a spraying distance of 10cm; the spraying pressure was 200kPa; and the mass ratio of PLGA polymer, PLLA polymer and solvent was 8:3:

89. This nanofiber wound dressing was printed at a spraying distance of 5 cm; the spraying pressure was 180 kPa; and the mass ratio of PLGA polymer, PLLA polymer, and solvent was 7:1:

92. The nanofiber wound dressing was printed at a spraying distance of 2 cm; the spraying pressure was 125 kPa; and the mass ratio of PLGA polymer, PLLA polymer and solvent was 4:2:

94.

2. The method for preparing a nanofiber wound dressing according to any one of claims 1, characterized in that, In step S1, the mixing method is ultrasonic mixing.

3. The method for preparing a nanofiber wound dressing according to any one of claims 1, characterized in that, In step S2, at least one layer of coating is applied.

4. The method for preparing a nanofiber wound dressing according to claim 1, characterized in that, The nanofiber wound dressing has 3-5 layers.

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