GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology and preparation method thereof

Abstract

The invention discloses a preparation method of a GEL / PEO / CA composite fiber medical dressing based on a coaxial microfluidic spinning technology, which comprises the following steps: (1) weighing a certain amount of GEL and PEO, and adding a proper amount of acetic acid solution to prepare a shell spinning solution; (2) weighing a certain amount of cinnamyl aldehyde and PEO, and adding a proper amount of an acetic acid solution to prepare a core layer spinning solution; (3) respectively extracting the two spinning solutions by using a 10ml injector, and forming a fiber membrane under a certain spinning condition by using a micro-fluidic nano-spinning machine; (4) drying for 12 hours in a vacuum environment at 25 DEG C; (5) carrying out gas-phase crosslinking by using a glutaraldehyde solution at normal temperature; and (6) carrying out vacuum drying to remove residual glutaraldehyde on the fiber membrane. The problems of high volatility of cinnamyl aldehyde and poorer water solubility of gelatin fibers in the prior art are fundamentally solved, and the fibers are endowed with efficient and long-lasting antibacterial, antioxidant and tissue regeneration promoting functions.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical composite materials, and particularly relates to a GEL / PEO / CA composite fiber medical dressing based on coaxial electrospinning technology and a preparation method thereof. Background Art

[0002] In recent years, the application of fiber materials in the biomedical field has been continuously expanding, and functional fiber materials have attracted much attention due to their excellent biological properties. Electrospinning technology has become an important means for preparing fibers with complex structures and specific functions due to its high precision and controllability. With the continuous development of medical composite material technology, various new types of wound dressings have been developed in the field of textile medicine, such as films, hydrocolloids, hydrogels, and micro / nanofibers. Among them, electrospun nanofiber membranes have broad prospects in the application field of wound dressings due to their inherent characteristics such as high specific surface area, high porosity, and structural similarity to the extracellular matrix of the skin.

[0003] As a natural polymer material, gelatin is widely used in medical and other fields due to its good biocompatibility. However, the structural retention of gelatin fibers is poor under humid conditions, and crosslinking is required to improve stability. Natural antibacterial agents such as cinnamaldehyde have multiple biological activities such as antibacterial and antioxidant properties, but their high volatility and poor water solubility limit their applications.

[0004] Compared with traditional drug-loading materials, micro / nanofibers with a core-shell structure can encapsulate drugs inside the fibers, which can not only encapsulate drugs well and maintain drug activity, but also effectively regulate the slow release of the encapsulated drugs due to the protection of the shell material, avoid burst release phenomena, and reduce the toxic and side effects of drugs. It can be seen that micro / nanofibers with a core-shell structure provide a direction for the preparation of multifunctional wound dressings. Currently, the technologies for preparing functional micro / nanofiber medical dressings with a core-shell structure using electrospinning technology are as follows:

[0005] CN111330063A discloses a nanofiber membrane and a preparation method thereof. The present invention discloses a nanofiber membrane with a core-shell structure. The core layer of the core-shell structure is honey and polyvinyl alcohol, and the shell layer is cinnamaldehyde and polycaprolactone; the nanofiber membrane is prepared by coaxial electrospinning.

[0006] CN117045846A discloses a high molecular weight chitosan core-shell structure micro / nanofiber dressing, which is prepared by formulating a spinning solution from high molecular weight chitosan, polyethylene oxide, acetic acid, and water, and then performing solution electrospinning. The core-shell structure has high molecular weight chitosan as the inner core and polyethylene oxide as the outer skin.

[0007] CN119326937A discloses an antibacterial hyaluronic acid wound dressing with a core-shell structure and its preparation method, belonging to the field of biomedical materials. In the present invention, the core-shell structure nanofibers are prepared by using the coaxial electrospinning technique, and this preparation method is superior to the solid structure nanofibers prepared by ordinary electrospinning.

[0008] As can be seen from the above patent technology, the existing wound dressings prepared from the core-sheath structure micro-nano fiber membranes for wound surfaces can all achieve the effects of slow release and wound healing promotion. At the same time, by utilizing different components and drug components added in the core-shell structure, various advantages are combined, enabling them to have multiple functions such as antibacterial, hemostatic, and anti-adhesion. However, there are still some defects in the electrospinning technology for preparing core-shell structure nanofiber wound dressings. For example, the existing dressings for wound surfaces mainly solve problems such as antibacterial, hemostatic, anti-adhesion, antioxidant, drug slow release, and promotion of wound repair. Of course, these are also important functions that fiber dressings must possess for skin wounds. However, for the current drug-loaded nanofiber dressings for wound surfaces, the most important purpose is to promote wound healing. Therefore, the absorption performance of wound exudate, the drug action concentration and its persistence, the tissue regeneration promotion performance, as well as antibacterial and antioxidant properties are the most important functions required for wound dressings. As is well known, the electrospinning process has very strict requirements for the spinning solution and spinning parameters. Uneven distribution of the electric field, uneven air flow, and uneven concentration of the polymer liquid are likely to result in uneven fiber diameters, or even beads. Moreover, it is not easy to precisely control the above parameters. If functional polymer additives and drugs are added to the spinning solution, it is easy to cause uneven distribution of the content of the additives and drugs in the core-sheath structure micro-nano fibers along the fiber length direction, and uneven functional distribution of the dressing is likely to occur after film formation. In addition, the functions of the core-sheath drug-loaded micro-nano fiber wound dressings are determined by adding different additives and drugs. The ratio and dosage of the additives and drugs are important factors affecting the functions of the wound dressings. Although the prior art has achieved the combination of functions in the fibers according to different polymer and drug combinations, for the changes in the environment and requirements needed during different stages of wound healing, precise matching of the dosage, ratio, and position of the functional polymers and drugs is required. Obviously, there is no report on this problem in the current research in the field of core-sheath drug-loaded micro-nano fiber wound dressings.

[0009] Therefore, how to effectively control the diameter uniformity of the core-sheath structure micro-nano fibers, achieve uniform functional distribution of the wound dressing, and at the same time, through precise matching and control of the dosage, ratio, and position of the functional polymers and drugs, help provide the required wound environment and requirements during different stages of wound healing, fundamentally solve the problems of high volatility of cinnamaldehyde and poor water solubility of gelatin fibers in the prior art, and endow the fibers with efficient and long-lasting antibacterial, antioxidant, and tissue regeneration promotion functions has become a difficult problem that needs to be urgently solved by those skilled in the field of functional fiber wound dressings. Summary of the Invention

[0010] Aiming at the deficiencies of the existing technology, the technical problem to be solved by the present invention is to provide a GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic electrospinning technology, which can achieve uniform functional distribution of the wound dressing, help provide the required wound surface environment and requirements during the healing process at different stages, and solve the problems of high volatility of cinnamaldehyde and poor water solubility of gelatin fibers, as well as its preparation method.

[0011] To solve the above technical problems, the technical solution adopted by the present invention is: a preparation method of a GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic electrospinning technology, comprising the following steps:

[0012] (1) Weigh a certain amount of GEL and PEO, add an appropriate amount of acetic acid solution, and prepare a shell spinning solution. The concentration of GEL in the spinning solution is 7.5 - 9.5 wt%, and the concentration of PEO is 5.5 - 7.5 wt%.

[0013] (2) Weigh a certain amount of cinnamaldehyde and PEO, add an appropriate amount of acetic acid solution, and prepare a core spinning solution. The concentration of cinnamaldehyde in the spinning solution is 3 - 7 wt%, and the concentration of PEO is 4 - 8 wt%.

[0014] (3) After respectively extracting the two spinning solutions with a 10 ml syringe, use a microfluidic electrospinning machine. Under certain electrospinning conditions, the spinning solution is extruded through a coaxial electrospinning needle and contacts the rotating collection plate. After being stretched and refined, a core - shell structured fiber is formed at the needle outlet and wound on the collection plate, and a fiber membrane is formed under room - temperature drying conditions.

[0015] (4) Dry the fiber membrane in a vacuum environment at 25°C for 12 hours to remove excess acetic acid and water.

[0016] (5) Put the fiber membrane into a fumigation pot, and perform gas - phase cross - linking with a 25 - 75% mv glutaraldehyde solution at room temperature for 6 - 12 h.

[0017] (6) Vacuum dry again to remove the residual glutaraldehyde on the fiber membrane, and obtain the GEL / PEO / CA composite fiber medical dressing.

[0018] In the above - mentioned preparation method of the GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic electrospinning technology, in the shell spinning solution of step (1), the concentration of GEL is 8.5 wt%, and the concentration of PEO is 6.4 wt%.

[0019] The preparation method of the GEL / PEO / CA composite fiber medical dressing based on the coaxial microfluidic spinning technology. In the acetic acid solution in step (1), the mass ratio of acetic acid to water is 4:1.

[0020] The preparation method of the GEL / PEO / CA composite fiber medical dressing based on the coaxial microfluidic spinning technology. In the core layer spinning solution in step (2), the concentration of cinnamaldehyde is 5 wt%, and the concentration of PEO is 6 wt%.

[0021] The preparation method of the GEL / PEO / CA composite fiber medical dressing based on the coaxial microfluidic spinning technology. In the acetic acid solution in step (2), the mass ratio of acetic acid to water is 5:4.

[0022] The preparation method of the GEL / PEO / CA composite fiber medical dressing based on the coaxial microfluidic spinning technology. In step (3), the spinning conditions are as follows: the advancing speed of the core layer spinning solution is 0.1 - 0.3 ml / h, the cortical spinning solution is 0.6 - 1.2 ml / h, the rotation speed of the collection plate is 200 - 400 r / min, the coaxial spinning needle specification is 30G / 21G, and the spinning humidity is 20 - 40%.

[0023] The preparation method of the GEL / PEO / CA composite fiber medical dressing based on the coaxial microfluidic spinning technology. In step (5), the concentration of the glutaraldehyde solution is 50% mv, and the crosslinking time is 9 h.

[0024] The preparation method of the GEL / PEO / CA composite fiber medical dressing based on the coaxial microfluidic spinning technology. In step (6), the vacuum drying time is set to 8 h.

[0025] The preparation method of the GEL / PEO / CA composite fiber medical dressing based on the coaxial microfluidic spinning technology. The advancing speed of the core layer spinning solution is 0.2 ml / h, the cortical spinning solution is 0.8 ml / h, the rotation speed of the collection plate is 300 r / min, and the spinning humidity is 30%.

[0026] A GEL / PEO / CA composite fiber medical dressing based on the coaxial microfluidic spinning technology, which is prepared by the above preparation method.

[0027] The advantages of the GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology and its preparation method of the present invention are as follows: First, the coaxial stretching spinning technology realizes the coaxial co-spinning of two or more fluids with different properties through a microfluidic chip. This technical point ensures the precise separation and synchronous spinning of the spinning solutions in the cortex and core layers, thus enabling the formation of composite fibers with a core-shell structure. This technology not only improves the controllability of the spinning process but also makes the composite fibers more uniform in structure and more diverse in performance. Second, in the design of the composite fibers, gelatin and PEO are selected as the cortex materials, making full use of the biocompatibility, degradability, and cell affinity of gelatin, as well as the stability and processability of PEO. At the same time, the spinning solution containing cinnamaldehyde is used as the core layer, and through precise regulation of the hydrodynamic parameters in the spinning process, the uniform distribution of cinnamaldehyde in the fibers is achieved. The present invention not only retains the excellent properties of gelatin but also endows the fibers with antibacterial, antioxidant, and tissue regeneration-promoting functions through the introduction of cinnamaldehyde. It effectively controls the diameter uniformity of the core-shell structured micro-nano fibers, realizes the uniform distribution of the functionality of the wound dressing, and at the same time, through the precise matching and control of the dosage, ratio, and position of the functional polymer and the drug, helps to provide the required wound environment and requirements for the wound healing process at different stages, fundamentally solving the problems of the high volatility of cinnamaldehyde and the poor water solubility of gelatin fibers in the prior art, and endowing the fibers with efficient and long-lasting antibacterial, antioxidant, and tissue regeneration-promoting functions. Description of the Drawings

[0028] Figure 1 It is the process flow chart for the preparation of the GEL / PEO / CA composite fiber medical dressing of the present invention;

[0029] Figure 2 It is the SEM image and diameter distribution diagram of the medical dressings prepared at different glutaraldehyde cross-linking times;

[0030] Figure 3 It is the TEM image of the medical dressing prepared in Example 2 of the present invention;

[0031] Figure 4 It is the FTIR-ATR spectrogram and XRD spectrogram of the medical dressings prepared at different glutaraldehyde cross-linking times;

[0032] Figure 5 It is the XPS-nitrogen spectrogram of the medical dressings prepared at different glutaraldehyde cross-linking times;

[0033] Figure 6 It is the stress-strain curve diagram of the medical dressings prepared at different glutaraldehyde cross-linking times;

[0034] Figure 7 It is the morphology diagram of the water droplet contact of the medical dressings prepared at different glutaraldehyde cross-linking times;

[0035] Figure 8 The water absorption rate test chart of the medical dressings prepared at different glutaraldehyde cross-linking times after being immersed in PBS for 24 hours;

[0036] Figure 9 The drug release performance test chart of the core-shell structured nanofibers in the medical dressing prepared in Example 2 of the present invention;

[0037] Figure 10 The antibacterial property test chart of the fibers with different cinnamaldehyde contents in the core liquid against Staphylococcus aureus and Escherichia coli;

[0038] Figure 11 The DPPH scavenging rate test chart of the medical dressings prepared with different cinnamaldehyde contents in the core liquid and different glutaraldehyde cross-linking times;

[0039] Figure 12 The hemolysis effect test chart and cytotoxicity test chart of the medical dressings prepared with different cinnamaldehyde concentrations. Detailed implementation manners

[0040] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0041] The GEL / PEO / CA fiber dressing of the present invention uses a microfluidic electrospinning machine (JNS-SBS-01, Nanjing Janus New Materials Co., Ltd.) to prepare a GEL / PEO / CA nanofiber dressing with a core-shell structure by using the microfluidic rotary electrospinning technology. The spinning solutions for the skin layer and the core layer are respectively prepared and stirred for eight hours to completely dissolve GEL, PEO, and CA to obtain a uniform spinning solution. The two prepared spinning solutions are respectively drawn with a 10 ml syringe, and the microfluidic electrospinning machine is used to control the ejection flow rate of the spinning solution. The shell liquid and the core liquid are respectively introduced into the outer channel and the inner channel of the coaxial electrospinning needle through a catheter. The spinning solution extruded from the needle contacts the rotating collection plate, and after undergoing a stretching and thinning process, a core-shell structured fiber is formed at the needle outlet and wound on the collection plate. A fiber membrane is formed under room temperature drying conditions and dried overnight to remove the residual solvent. The fiber membrane is placed in a fumigation pot and subjected to gas-phase cross-linking with a glutaraldehyde solution at room temperature. After cross-linking, it is placed in a vacuum drying oven for eight hours to remove the residual glutaraldehyde on the fiber membrane.

[0042] As Figure 1 shown, a preparation method of a GEL / PEO / CA composite fiber medical dressing based on the coaxial microfluidic electrospinning technology includes the following steps:

[0043] (1) Weigh a certain amount of GEL and PEO, add an appropriate amount of acetic acid solution, and prepare the shell spinning solution. The spinning solution is stirred on a magnetic stirrer at room temperature for 8 hours until completely dissolved to obtain a uniform spinning solution. The concentration of GEL in the spinning solution is 7.5 - 9.5 wt%, and the concentration of PEO is 5.5 - 7.5 wt%.

[0044] (2) Weigh a certain amount of cinnamaldehyde and PEO, add an appropriate amount of acetic acid solution, and prepare the core spinning solution. The spinning solution is stirred on a magnetic stirrer at room temperature for 8 hours until completely dissolved to obtain a uniform spinning solution. The concentration of cinnamaldehyde in the spinning solution is 3 - 7 wt%, and the concentration of PEO is 4 - 8 wt%.

[0045] (3) After separately extracting the two spinning solutions with a 10 ml syringe, use a microfluidic electrospinning machine. Under certain spinning conditions, the spinning solution is extruded through a coaxial spinning needle and contacts the rotating collection plate. After being stretched and refined, a core - shell structure fiber is formed at the needle outlet and wound around the collection plate, and a fiber membrane is formed under room - temperature drying conditions.

[0046] (4) Dry the fiber membrane in a vacuum environment at 25 °C for 12 hours to remove excess acetic acid and water.

[0047] (5) Place the fiber membrane in a fumigation pot and perform gas - phase cross - linking with a 25 - 75% mv glutaraldehyde solution at room temperature. The cross - linking time is 6 - 12 h.

[0048] (6) Vacuum dry again to remove the residual glutaraldehyde on the fiber membrane to obtain the GEL / PEO / CA composite fiber medical dressing.

[0049] Among them, the materials used in the product: porcine skin gelatin (Gel, gel strength 300, type A, CAS: 9000 - 70 - 8) is purchased from Sigma - Aldrich Company, poly(ethylene oxide) (PEO, MV = 600000, powder, CAS: 68441 - 17 - 8), cinnamaldehyde (CA, 98%, CAS: 104 - 55 - 2) and glutaraldehyde (high - purity medical grade, 50%, CAS: 111 - 30 - 8) are purchased from Shanghai Macklin Biochemical Technology Co., Ltd. Acetic acid (analytical pure AR, CAS: 64 - 19 - 7) is purchased from Sinopharm Chemical Reagent Co., Ltd.

[0050] The antibacterial dressing of the present invention uses gelatin and PEO as the cortical material, and PEO and cinnamaldehyde as the core material, overcoming the problem in the prior art that the active substances or drug components in the dressing are affected by the wound microenvironment and it is difficult to maintain the promotion of repair and growth. It makes full use of the biocompatibility, degradability and cell affinity of gelatin, as well as the stability and processability of PEO, and the uniform distribution and slow-release performance of cinnamaldehyde in the fibers. It not only avoids the influence of the wound environment on the drug and the polymer, but also solves the problem of the fast drug release rate at the initial stage of using the drug-loaded medical dressing, improving the functionality and quality of the wound dressing. At the same time, the polymer and gelatin are used to effectively absorb tissue exudate, keep the wound surface moist, avoid the problem of wound adhesion, and further promote the healing of the wound surface.

[0051] The following specifically describes the present application through specific embodiments. The following embodiments are only partial embodiments of the present application and do not limit the present application.

[0052] Example 1:

[0053] A preparation method of a GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology includes the following steps:

[0054] (1) Weigh a certain amount of GEL and PEO, add an appropriate amount of acetic acid solution, and prepare the shell spinning solution. The concentration of GEL in the spinning solution is 7.5 wt%, the concentration of PEO is 5.5 wt%, and in the acetic acid solution, the mass ratio of acetic acid to water is 4:1;

[0055] (2) Weigh a certain amount of cinnamaldehyde and PEO, add an appropriate amount of acetic acid solution, and prepare the core spinning solution. The concentration of cinnamaldehyde in the spinning solution is 3 wt%, the concentration of PEO is 4 wt%, and in the acetic acid solution, the mass ratio of acetic acid to water is 5:4;

[0056] (3) After respectively extracting the two spinning solutions with a 10 ml syringe, use a microfluidic nano-spinning machine, set the core spinning solution propulsion speed to 0.1 ml / h, the cortical spinning solution to 0.6 ml / h, the collection plate rotation speed to 200 r / min, the coaxial spinning needle specification to 30G / 21G, the spinning humidity to 20%, and the spinning solution is extruded through the coaxial spinning needle and contacts the rotating collection plate. After being stretched and refined, a core-shell structured fiber is formed at the needle outlet and wound on the collection plate, and a fiber membrane is formed under room temperature drying conditions;

[0057] (4) Dry the fiber membrane in a vacuum environment at 25°C for 12 hours to remove excess acetic acid and water;

[0058] (5) Put the fiber membrane into a fumigation pot and carry out gas-phase cross-linking with a 25% mv glutaraldehyde solution at room temperature for 12 hours;

[0059] (6) Remove the residual glutaraldehyde on the fiber membrane by vacuum drying for another 8 h to obtain the GEL / PEO / CA composite fiber medical dressing.

[0060] The GEL / PEO / CA composite fiber medical dressing of the present invention based on the coaxial microfluidic spinning technology is prepared by the above preparation method of this example.

[0061] Example 2:

[0062] A preparation method of a GEL / PEO / CA composite fiber medical dressing based on the coaxial microfluidic spinning technology comprises the following steps:

[0063] (1) Weigh a certain amount of GEL and PEO, add an appropriate amount of acetic acid solution, and prepare the shell spinning solution. The concentration of GEL in the spinning solution is 8.5 wt%, the concentration of PEO is 6.4 wt%, and in the acetic acid solution, the mass ratio of acetic acid to water is 4:1;

[0064] (2) Weigh a certain amount of cinnamaldehyde and PEO, add an appropriate amount of acetic acid solution, and prepare the core spinning solution. The concentration of cinnamaldehyde in the spinning solution is 5 wt%, the concentration of PEO is 6 wt%, and in the acetic acid solution, the mass ratio of acetic acid to water is 5:4;

[0065] (3) After respectively extracting the two spinning solutions with a 10 ml syringe, use a microfluidic nano-spinning machine. Set the core spinning solution propulsion speed to 0.2 ml / h, the cortical spinning solution to 0.8 ml / h, the collection plate rotation speed to 300 r / min, the coaxial spinning needle specification to 30G / 21G, and the spinning humidity to 30%. After the spinning solution is extruded through the coaxial spinning needle and contacts the rotating collection plate, it forms a core-shell structure fiber at the needle outlet after stretching and refinement and winds around the collection plate, and forms a fiber membrane under room temperature drying conditions;

[0066] (4) Dry the fiber membrane in a vacuum environment at 25 °C for 12 hours to remove the excess acetic acid and water;

[0067] (5) Put the fiber membrane into a fumigation pot and carry out gas-phase cross-linking with a 50% mv glutaraldehyde solution at room temperature for 9 h;

[0068] (6) Remove the residual glutaraldehyde on the fiber membrane by vacuum drying for another 8 h to obtain the GEL / PEO / CA composite fiber medical dressing.

[0069] The GEL / PEO / CA composite fiber medical dressing of the present invention based on the coaxial microfluidic spinning technology is prepared by the above preparation method of this example.

[0070] Example 3:

[0071] A preparation method of a GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology, comprising the following steps:

[0072] (1) Weigh a certain amount of GEL and PEO, add an appropriate amount of acetic acid solution, and prepare a shell spinning solution. The concentration of GEL in the spinning solution is 9.5 wt%, the concentration of PEO is 7.5 wt%, and in the acetic acid solution, the mass ratio of acetic acid to water is 4:1;

[0073] (2) Weigh a certain amount of cinnamaldehyde and PEO, add an appropriate amount of acetic acid solution, and prepare a core spinning solution. The concentration of cinnamaldehyde in the spinning solution is 7 wt%, the concentration of PEO is 8 wt%, and in the acetic acid solution, the mass ratio of acetic acid to water is 5:4;

[0074] (3) After respectively extracting the two spinning solutions with a 10 ml syringe, use a microfluidic nano-spinning machine, set the core spinning solution propulsion speed to 0.3 ml / h, the cortical spinning solution to 1.2 ml / h, the collection plate rotation speed to 400 r / min, the coaxial spinning needle specification to 30G / 21G, the spinning humidity to 40%. After the spinning solution is extruded through the coaxial spinning needle and contacts the rotating collection plate, it forms a core-shell structure fiber at the needle outlet after stretching and refinement and winds around the collection plate, and forms a fiber membrane under room temperature drying conditions;

[0075] (4) Dry the fiber membrane in a vacuum environment at 25 °C for 12 hours to remove excess acetic acid and water;

[0076] (5) Put the fiber membrane into a fumigation pot, and carry out gas-phase cross-linking with a 75% mv glutaraldehyde solution at room temperature, and the cross-linking time is 6 h;

[0077] (6) Vacuum dry again for 8 h to remove the residual glutaraldehyde on the fiber membrane, and obtain the GEL / PEO / CA composite fiber medical dressing.

[0078] The GEL / PEO / CA composite fiber medical dressing of the present invention based on coaxial microfluidic spinning technology is prepared by the above preparation method of this embodiment.

[0079] The performance test results of the GEL / PEO / CA composite fiber medical dressing of the present invention based on coaxial microfluidic spinning technology are as follows:

[0080] 1. Regarding the fiber morphology:

[0081] As Figure 2 shown, wherein, Figure 2 a - e are respectively the SEM diagrams and diameter distribution diagrams of each GEL / PEO / CA composite fiber medical dressing prepared under the basic conditions of Example 2 under the conditions of 0 h, 3 h, 6 h, 9 h, and 12 h of glutaraldehyde cross-linking. From Figure 2It can be seen that all the fiber morphologies are uniform, without droplets and beads, and are arranged in the same direction. When the glutaraldehyde cross-linking time changes from 0 hour to 12 hours, the average diameter of the fibers changes from 1.85±0.12μm to 2.21±0.25μm, the uniformity decreases, and the fibers show a certain degree of swelling and curling. These changes in microscopic morphology with reaction time are mainly due to the reaction of glutaraldehyde molecules with the amino groups (-NH 2 ) on the gelatin molecular chain to form a Schiff base structure -RC=N-, causing adhesion between the fibers. The longer the cross-linking time, the larger the diameter and the degree of fiber bending, and a large number of fibers stick together, gradually forming a dense network structure.

[0082] As Figure 3 shown, the skin-core structure of the fibers was confirmed by TEM images, and the results showed that the core layer was well wrapped by the cortex, and the skin-core fiber structure was evenly distributed inside and outside.

[0083] As Figure 4 shown, among them, Figure 4 (a) is the amide A band spectrum of Gel, Figure 4 (b) is the amide I, II, and III band spectra of Gel. Figure 4 (c) is the XRD spectrum under different glutaraldehyde cross-linking times. Figure 4 (d) is the XRD spectra of Gel and PEO. The FTIR-ATR spectra of the glutaraldehyde cross-linked Gel / PEO / Ca fiber membrane are as Figure 4 (a). All samples have a broad absorption peak at 3296 cm -1 , corresponding to the stretching vibrations of O-H and N-H. However, as the cross-linking time prolongs, the intensity of this peak gradually decreases. This may be due to the reaction of the free amino groups in the Gel / PEO / Ca fibers with the aldehyde groups in glutaraldehyde. The greater the cross-linking degree, the more the amino groups on the fiber surface are consumed. In addition, in Figure 4 (b), all FTIR spectra show three characteristic absorption peaks at 1636 cm -1 , 1538 cm -1 and 1466 cm -1 , corresponding to the Gel amide I band (C=O stretching vibration), Gel amide II band (N-H bending vibration and C-N stretching vibration), and Gel amide III band (C=O bending vibration and C-N stretching vibration), respectively. As the glutaraldehyde cross-linking time prolongs, the peak intensities of these characteristic peaks gradually decrease. These changes also confirm the cross-linking effect of glutaraldehyde on the Gel / PEO / Ca fibers, reducing the number of free amino groups.

[0084] The X-ray diffraction pattern (XRD) is as Figure 4(c) and (d) show that the aggregate structure of nanofibers was studied. In the Gel diffraction pattern, a broad characteristic peak was observed at 20°. For the diffraction pattern of PEO, due to the crystalline nature of PEO, two sharp peaks were observed at 2θ = 19.2° and 23.3°. In the fiber membrane sample without glutaraldehyde cross-linking, three distinct characteristic peaks appeared at 15.3°, 19.0° and 22.5°, which did not coincide with the diffraction bands of pure PEO and Gel, indicating that a new molecular structure was formed by the interaction between PEO and CS macromolecules. With the increase of glutaraldehyde cross-linking time, the intensities of the three characteristic peaks at 15.3°, 19.0° and 22.5° decreased to varying degrees and the peak positions shifted to the right. The reason is that the cross-linking of glutaraldehyde changed the triple helix structure of gelatin macromolecules, resulting in a decrease in crystallinity. The longer the cross-linking time, the smaller the diffraction peak intensity. The possible reason is that the higher the cross-linking degree, the tighter the network structure, further destroying the crystal structure of the fiber membrane and reducing the crystallinity.

[0085] As Figure 5 shown, XPS was used to determine the types and contents of chemical bonds on the sample surface. With the extension of cross-linking time, new peaks appeared in the N spectrum, which were unsaturated N bonds with higher energy than -NH 2 , and this was the reaction between glutaraldehyde molecules and amino groups (-NH 2 ) on the gelatin molecular chain to form a new Schiff base structure -RC=N-.

[0086] 2. Regarding physical properties:

[0087] As Figure 6 shown, the stress-strain curve can show that the tensile strength of the GEL / PEO / CA fiber membrane is about 1 MPa. After glutaraldehyde cross-linking treatment, the tensile strength of the fiber membrane increased significantly, reaching 3 - 4 MPa, meeting the requirements of wound dressings. The cross-linking reaction formed a chemical bond network inside the gelatin fibers, making the intermolecular forces between the fiber molecular chains increase significantly. When the fiber is stretched by an external force, these chemical bond networks can effectively resist the tensile force, thereby increasing the tensile strength of the fiber. The elongation at break of the fiber membrane is about 0.5%, and the toughness is low.

[0088] As Figure 7 shown, where Figure 7 a - e are the morphological diagrams of the water droplets in contact with the medical dressings prepared under the conditions of cross-linking time of 0 h, 3 h, 6 h, 9 h, and 12 h respectively. As is well known, wettability is crucial for the dressing to maintain an appropriate moist wound environment, and the water contact angle (WCA) in the range of 0 - 80° is necessary for cell adhesion and proliferation during wound healing. As Figure 7As shown in a - e, the initial WCA was 48.2°. After glutaraldehyde cross - linking treatment, as the cross - linking time extended, the WCA increased to 88°, achieving a slightly hydrophilic effect( Figure 7 e), indicating a decrease in wettability. This is because when using glutaraldehyde as a cross - linker to treat gelatin fibers, the cross - linking reduces the exposure number of hydrophilic groups (such as hydroxyl and amino groups) in gelatin molecules, making it more difficult for water molecules to interact with the surface of gelatin fibers. With the increase in the glutaraldehyde cross - linking degree, the hydrophilicity of the gelatin fiber membrane will further decrease. This is because the high cross - linking degree makes the interaction between gelatin molecular segments more compact, restricting the penetration and diffusion of water molecules. Due to the decrease in hydrophilicity, the contact angle of the gelatin fiber membrane will increase correspondingly.

[0089] As Figure 8 shown, good absorbency is another important feature of wound dressings. It can enable the dressing to promptly absorb wound exudates, create a better micro - environment, and promote wound healing. The water absorption rate of the dressing was measured after soaking in PBS buffer for 24 h, as Figure 6 shown. All samples showed a high water absorption rate > 300%. At the same time, as the glutaraldehyde treatment time extended, the water absorption rate of the nanofiber dressing decreased slowly, with the most significant decrease at 9 hours. This is because ① reduction of hydrophilic groups: The cross - linking reaction consumes hydrophilic groups (such as hydroxyl and amino groups) in gelatin molecules, resulting in a decrease in the exposure number of these groups on the fiber surface. Hydrophilic groups are the main sites for attracting water molecules, and their reduction leads to a decrease in the water absorption rate of the fiber. ② Network structure restriction: The cross - linked network - like structure restricts the entry and diffusion of water molecules, making it more difficult for water molecules to penetrate into the fiber interior, thus reducing the water absorption rate. ③ The higher the cross - linking degree, the closer the connection between gelatin molecules, and the denser the formed network structure. This further restricts the penetration and diffusion of water molecules, resulting in a further decrease in the water absorption rate.

[0090] 3. Regarding the drug sustained - release effect:

[0091] As Figure 9 shown, among them, Figure 9 (a) is the linear relationship graph of the ultraviolet absorbance of cinnamaldehyde and concentration, Figure 9 (b) is the curve graph of the sustained - release concentration of cinnamaldehyde in nanofibers changing with time. As Figure 9 (a) shown, the absorbance of a solution with a known cinnamaldehyde concentration was tested by ultraviolet spectrophotometry, and the linear relationship equation between ultraviolet absorbance and cinnamaldehyde concentration was established. The sustained - release effect of cinnamaldehyde concentration in the core - shell structure fiber was measured, as Figure 9(b), on the eighth day, cinnamaldehyde was basically completely released, and the concentration reached 1.05 mg / L. Research shows that this reaches the optimal concentration for cinnamaldehyde to promote cell growth. The core-shell structure fiber can continuously and stably release drugs, ensuring that the wound site maintains an effective drug concentration for a long time. This continuous release property helps to reduce the dosing frequency while maintaining a long-term antibacterial effect, improving the comfort of patients.

[0092] 4. Regarding antibacterial properties:

[0093] Preventing bacterial infection is a necessary condition for wound healing. The antibacterial rates of the dressing against Staphylococcus aureus and Escherichia coli were evaluated. As Figure 10 shown, for Staphylococcus aureus, the antibacterial rates were 98.51%, 99.50%, and 99.99% when the cinnamaldehyde concentration in the core liquid was 3%, 5%, and 7% respectively. For Escherichia coli, the antibacterial rates were 99.73%, 99.93%, and 99.99% when the cinnamaldehyde concentration in the core liquid was 3%, 5%, and 7% respectively. There were dense colonies on the agar plate of the control sample. This is because the aldehyde group present in the cinnamaldehyde molecule is a nucleophilic group, which is easily adsorbed by the hydrophilic group on the bacterial surface and penetrates the cell wall. Cinnamaldehyde can destroy the cell wall polysaccharide structure of bacteria and fungi, thus achieving the effect of antibacterial or bactericidal. Since mammals do not have cell walls, cinnamaldehyde will not cause damage to human and animal cells. It can not only destroy the cell structure, but also act with proteins and enzymes in bacteria, interfering with the normal physiological metabolism of bacteria, and further playing an antibacterial or bactericidal role.

[0094] 5. Regarding antioxidant properties:

[0095] As Figure 11 shown, among them Figure 11 (a) is the DPPH scavenging rate test chart when the cinnamaldehyde content in the core liquid of the spinning solution is 3 wt% and 5 wt%, Figure 11 (b) is the DPPH scavenging rate of the wound dressings prepared under glutaraldehyde cross-linking times of 3 h, 6 h, and 9 h. The antioxidant activity of the wound dressing of the present invention is determined by the scavenging rate of DPPH. Figure 11(a) shows that the greater the cinnamaldehyde content in the spinning solution core liquid, the stronger the antioxidant performance of the dressing, and the maximum DPPH scavenging rate can exceed 90%. This is because the aldehyde group of cinnamaldehyde can react with free radicals to form stable compounds, thus scavenging free radicals in the wound surface. Wound dressings with antioxidant activity can promote wound healing because neutrophils and white blood cells aggregate at the injury site and attack microorganisms through phagocytosis. During the wound healing process, excessive free radicals are generated at the wound site, which can disrupt the oxidation / antioxidant balance of cells, leading to enzyme inactivation, lipid peroxidation, and DNA breakage, causing skin damage and expansion around the wound and slowing down wound healing. The benzene ring structure of cinnamaldehyde can interact with proteases, thus affecting their activity, helping to regulate the intracellular redox state, and further exerting antioxidant effects. As Figure 11 (b), as the glutaraldehyde crosslinking time increases, the time required for the antioxidant performance of the fiber membrane to reach the maximum becomes longer, that is, the cinnamaldehyde release rate is slower. Therefore, the appropriate cinnamaldehyde sustained-release rate can be selected by controlling the glutaraldehyde crosslinking time to deal with different wounds.

[0096] 6. Regarding the effect of promoting tissue regeneration:

[0097] As Figure 12 shown, among them, Figure 12 (a) is the hemolysis effect test chart of fiber membranes with different cinnamaldehyde concentrations, Figure 12 (b) is the cytotoxicity determination chart of fiber membranes with different cinnamaldehyde concentrations by the cck-8 method. In Figure 12 (a), the hemolysis effect of the fiber membrane was measured. When the core layer cinnamaldehyde concentration of the fiber membrane was 3% and 5%, there was no hemolysis effect, which was the same as the blank control group, but there was a small amount of hemolysis effect when the concentration was 7%. Cytotoxicity is an important requirement for biomedical materials. The in vitro cytotoxicity of the fiber membrane was evaluated using L929 cells because fibroblasts play a key role in the wound healing process. As Figure 12 (b) shows, at 24 h, the survival rates of L929 cells of fiber membranes with core layer cinnamaldehyde concentrations of 3% and 5% both exceeded 100%, while the survival rates of some groups with a concentration of 7% were lower than 100%. This indicates that the fiber membrane has no cytotoxicity and can promote cell proliferation when the core layer cinnamaldehyde concentration is 3% and 5%, while it has a small amount of cytotoxicity when the concentration is 7%.

[0098] In summary, to solve the problems existing in the prior art, the present invention uses the coaxial stretching spinning technology to perform coaxial co-spinning through a microfluidic chip, and forms composite fibers with a core-shell structure through the stretching force. The advantages of different materials are fully utilized to achieve the diversification of fiber structures and functions. The application of the coaxial stretching spinning technology and the careful design of the composite fibers together constitute the core innovation points of this technical solution, making the prepared gelatin-cinnamaldehyde composite fibers have broad application prospects in the biomedical field.

[0099] Of course, the above description is not a limitation of the present invention, and the present invention is not limited to the above examples. Any changes, modifications, additions or substitutions made by those of ordinary skill in the art within the scope of the essence of the present invention shall fall within the protection scope of the present invention.

Claims

1. A method for preparing a GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology, characterized in that: The steps include: (1) Weigh a certain amount of GEL and PEO, add an appropriate amount of acetic acid solution, and prepare a shell spinning solution, wherein the concentration of GEL in the spinning solution is 7.5-9.5wt%, and the concentration of PEO is 5.5-7.5wt%; (2) Weigh a certain amount of cinnamaldehyde and PEO, add an appropriate amount of acetic acid solution, and prepare a core layer spinning solution, wherein the concentration of cinnamaldehyde in the spinning solution is 3-7wt%, and the concentration of PEO is 4-8wt%; (3) After the two spinning solutions were drawn out with a 10 ml syringe respectively, a microfluidic nanospinning machine was used. Under certain spinning conditions, the spinning solutions were extruded through a coaxial spinning needle and contacted with a rotating collecting plate. After being stretched and refined, a skin-core structure fiber was formed at the needle outlet and wound on the collecting plate, and a fiber membrane was formed under room temperature drying conditions; (4) Dry the fiber membrane in a vacuum environment at 25°C for 12 hours to remove excess acetic acid and water; (5) Place the fiber membrane in a fumigation pot and perform vapor phase crosslinking with a 25-75% mv glutaraldehyde solution at room temperature for 6-12 hours; (6) Vacuum drying was performed again to remove the residual glutaraldehyde on the fiber membrane to obtain the GEL / PEO / CA composite fiber medical dressing.

2. The method for preparing the GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology according to claim 1, characterized in that: In the shell spinning solution of step (1), the concentration of GEL is 8.5wt%, and the concentration of PEO is 6.4wt%.

3. The method for preparing the GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology according to claim 1, characterized in that: In the acetic acid solution of step (1), the mass ratio of acetic acid to water is 4:

1.

4. The method for preparing the GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology according to claim 1, characterized in that: In the core layer spinning solution of step (2), the concentration of cinnamaldehyde is 5wt%, and the concentration of PEO is 6wt%.

5. The method for preparing the GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology according to claim 1, characterized in that: In the acetic acid solution of step (2), the mass ratio of acetic acid to water is 5:

4.

6. The method for preparing the GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology according to claim 1, characterized in that: In the step (3), the spinning conditions are as follows: the core layer spinning solution advancing speed is 0.1-0.3 ml / h, the skin layer spinning solution is 0.6-1.2 ml / h, the collecting plate rotation speed is 200-400 r / min, the coaxial spinning needle specification is 30G / 21G, and the spinning humidity is 20-40%.

7. The method for preparing the GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology according to claim 1, characterized in that: In the step (5), the concentration of the glutaraldehyde solution is 50% mv, and the cross-linking time is 9 h.

8. The method for preparing the GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology according to claim 1, characterized in that: In the step (6), the vacuum drying time is set to 8 hours.

9. The method for preparing the GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology according to claim 6, characterized in that: The core layer spinning solution advancing speed is 0.2 ml / h, the skin layer spinning solution is 0.8 ml / h, the collecting plate rotating speed is 300 r / min, and the spinning humidity is 30%.

10. A GEL / PEO / CA composite fiber medical dressing based on coaxial microfluidic spinning technology, characterized in that: Prepared by the preparation method according to any one of claims 1 to 9.

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