Adhesive hydrogel fiber composite membrane adaptive to mechanical properties of dynamic organs as well as preparation method and application of adhesive hydrogel fiber composite membrane

Abstract

The invention provides an adhesive hydrogel fiber composite membrane adaptive to mechanical properties of dynamic organs as well as a preparation method and application of the adhesive hydrogel fiber composite membrane, and relates to the technical field of medical biological materials. The adhesive hydrogel fiber composite membrane adaptive to the mechanical properties of the dynamic organs comprises a micron fiber network support layer and electrostatic spinning nanofiber membrane layers deposited on the surfaces of the two sides of the micron fiber network support layer and in a pore structure, at least the electrostatic spinning nanofiber membrane layer on the surface of one side of the micron fiber network support layer is loaded with porous self-gel powder. After the hydrogel fiber composite membrane with the sandwich structure is in contact with biological tissues and absorbs interface water, rapid gelation is carried out in situ to form a hydrogel layer, relatively strong tissue adhesive force is realized, and meanwhile, the micron fiber bracket of the middle layer keeps mechanical strength and nonlinear mechanical elasticity. The hydrogel fiber composite membrane provided by the invention can simultaneously meet the strong adhesiveness of wet tissues and the biomechanical properties of adaptive dynamic organs.

Description

Technical Field

[0001] The present invention relates to the technical field of medical biomaterials, and in particular to an adhesive hydrogel fiber composite membrane adapted to the mechanical properties of dynamic organs, and a preparation method and application thereof. Background Art

[0002] Current tissue adhesives, generally in liquid or wet gel state, mainly rely on their molecules (such as monomers, macromolecules or polymers) to form covalent / non-covalent bonds with the polymer network of the tissue through the diffusion of interfacial water. The strong adhesion properties of tissue adhesives in the wet gel state mainly depend on the balance between the hydrogel cohesion and the interfacial bonding strength. Improving adhesion performance is often at the expense of hydrogel cohesion (mechanical properties), and vice versa. Although many bioadhesive hydrogels have been reported, these materials generally exhibit considerable mechanical differences compared to natural tissues. It remains a major challenge for hydrogel adhesives to meet the mechanical properties required for specific applications, such as adapting to dynamic organs, while maintaining strong adhesion to the target tissue. Summary of the invention

[0003] In view of this, the purpose of the present invention is to provide an adhesive hydrogel fiber composite membrane adapted to the mechanical properties of dynamic organs and its preparation method and application. The hydrogel fiber composite membrane provided by the present invention can simultaneously meet the strong adhesion of wet tissue and the biomechanical properties adapted to dynamic organs.

[0004] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0005] The present invention provides an adhesive hydrogel fiber composite membrane adapted to the mechanical properties of dynamic organs, comprising a micron fiber network scaffold layer, an electrospun nanofiber membrane layer deposited on both side surfaces and in a pore structure of the micron fiber network scaffold layer, wherein at least the electrospun nanofiber membrane layer on one side surface of the micron fiber network scaffold layer is loaded with porous self-gelling powder; the fibers of the micron fiber network scaffold layer and the electrospun nanofiber membrane layer are both polycaprolactone fibers.

[0006] Preferably, the fiber diameter of the micron fiber network scaffold layer is 1 to 10 μm, and the number of fiber layers is 1 to 50.

[0007] Preferably, the geometric structure of each fiber layer in the micron fiber network scaffold layer independently includes an expansion structure or a non-expansion structure, the expansion structure includes a concave angle honeycomb network structure, a sinusoidal network structure or a diamond truss network structure, and the non-expansion structure includes a quadrilateral network structure or a hexagonal network structure.

[0008] Preferably, the thickness of the electrospun nanofiber membrane layer is 50-200 μm; the fiber diameter of the electrospun nanofiber membrane layer is 500 nm-1 μm.

[0009] Preferably, the average particle size of the porous self-gel powder is 1 to 10 μm, and the porous self-gel powder is a composite gel powder formed by polyacrylic acid and polyethyleneimine.

[0010] Preferably, the mass content of the porous self-gelling powder in the electrospun nanofiber membrane layer loaded with the porous self-gelling powder is 50-80%.

[0011] The present invention provides a method for preparing an adhesive hydrogel fiber composite membrane adapted to dynamic organ mechanical properties as described in the above technical solution, comprising the following steps:

[0012] The polycaprolactone was subjected to MEW printing to obtain a micron fiber network scaffold layer;

[0013] dissolving polycaprolactone in an organic solvent to obtain a spinning solution;

[0014] The spinning solution is used to electrospin the two side surfaces of the micron fiber network scaffold layer and spray porous self-gel powder respectively to obtain the adhesive hydrogel fiber composite membrane adapted to the dynamic organ mechanical properties; the spraying of porous self-gel powder is carried out at least during the process of electrospinning one side surface of the micron fiber network scaffold layer.

[0015] Preferably, the conditions for MEW printing include: heating polycaprolactone to form a polycaprolactone melt, the pumping pressure of the polycaprolactone melt is 0.2-1 bar, the distance from the print head to the receiving plate is 3-4 mm, the applied voltage is 3-5 kV, and the printing speed is 1000-1500 mm / min.

[0016] Preferably, the concentration of the spinning solution is 10-12% w / v, and the conditions for electrospinning include: the flow rate of the spinning solution is 0.8-1 mL / h, the distance from the spinning needle to the receiving plate is 15-20 cm, the spinning voltage is 15-20 kV, the micron fiber network support layer is placed between the spinning needle and the receiving plate, and the distance between the micron fiber network support layer and the receiving plate is 5-10 cm.

[0017] The present invention provides the use of the adhesive hydrogel fiber composite membrane adapted to the dynamic mechanical properties of organs described in the above technical scheme or the adhesive hydrogel fiber composite membrane adapted to the dynamic mechanical properties of organs prepared by the preparation method described in the above technical scheme in the preparation of tissue repair and / or regeneration materials, dynamic wound sealing materials, hemostatic and antibacterial materials and drug delivery materials.

[0018] The present invention provides an adhesive hydrogel fiber composite membrane adapted to the mechanical properties of dynamic organs, comprising a micron fiber network scaffold layer, an electrospun nanofiber membrane layer deposited on both sides of the micron fiber network scaffold layer and in a pore structure, wherein at least the electrospun nanofiber membrane layer on one side of the micron fiber network scaffold layer is loaded with porous self-gelling powder; the fibers of the micron fiber network scaffold layer and the electrospun nanofiber membrane layer are both polycaprolactone fibers. The hydrogel fiber composite membrane provided by the present invention has a "sandwich" structure, wherein the middle layer is a micron fiber network scaffold, which can be anisotropic by regulating the fiber diameter and the scaffold geometric structure design parameters, so as to achieve personalized adaptation to the mechanical strength and nonlinear mechanical elasticity of dynamic organs; the surface of the micron fiber network scaffold layer is an electrospun nanofiber membrane loaded with porous self-gelling powder, and the porous self-gelling powder will quickly gel in situ to form a hydrogel layer after absorbing tissue interface water, and the functional groups in the polymer network at the hydrogel-tissue interface interact with each other to achieve strong tissue adhesion. The hydrogel fiber composite membrane provided by the present invention can simultaneously meet the strong adhesion of wet tissue and the biomechanical properties of adapting to dynamic organs, and has broad application prospects in the fields of tissue repair and regeneration, dynamic wound sealing, hemostatic and antibacterial materials, and drug delivery. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The schematic diagram of the overall structure of the adhesive hydrogel fiber composite membrane adapted to the dynamic organ mechanical properties provided by the present invention is as follows: Figure 1 1-micrometer fiber network scaffold layer, 2-electrospun nanofiber membrane layer;

[0020] Figure 2 Schematic diagram of the geometric structure in the micron fiber network scaffold layer. Figure 2 (a) is a tensile structure (recessed angle honeycomb network structure, sinusoidal network structure, diamond truss network structure), (b) is a non-tensile structure (quadrilateral network structure, hexagonal network structure);

[0021] Figure 3 This is a scanning electron microscope image of the MEW micron fiber network scaffold with a sinusoidal structure in Example 1;

[0022] Figure 4 1 and 2 are stress-strain curves of the MEW micron fiber network scaffold with sinusoidal structure in Example 1 along the major axis and minor axis directions respectively. DETAILED DESCRIPTION

[0023] The present invention provides an adhesive hydrogel fiber composite membrane adapted to the mechanical properties of dynamic organs, comprising a micron fiber network scaffold layer, an electrospun nanofiber membrane layer deposited on both side surfaces and in a pore structure of the micron fiber network scaffold layer, wherein at least the electrospun nanofiber membrane layer on one side surface of the micron fiber network scaffold layer is loaded with porous self-gelling powder; the fibers of the micron fiber network scaffold layer and the electrospun nanofiber membrane layer are both polycaprolactone fibers.

[0024] Figure 1 The schematic diagram of the overall structure of the adhesive hydrogel fiber composite membrane adapted to the dynamic organ mechanical properties provided by the present invention is as follows: Figure 1 1-micrometer fiber network scaffold layer, 2-electrospinning nanofiber membrane layer. The adhesive hydrogel fiber composite membrane adapted to the dynamic organ mechanical properties provided by the present invention has a "sandwich" structure, which is described in detail below.

[0025] The adhesive hydrogel fiber composite membrane adapted to the dynamic organ mechanical properties provided by the present invention includes a micron fiber network scaffold layer. In the present invention, the fiber of the micron fiber network scaffold layer is polycaprolactone (PCL) fiber. In the present invention, the fiber diameter of the micron fiber network scaffold layer is preferably 1 to 10 μm, specifically 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 μm, and the number of fiber layers is preferably 1 to 50 layers, specifically 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 layers; the thickness of the micron fiber network scaffold layer is the product of the fiber diameter and the number of fiber layers.

[0026] In the present invention, the geometric structure of each fiber layer in the micron fiber network scaffold layer preferably includes an auxetic structure or a non-auxetic structure, the auxetic structure preferably includes a concave angle honeycomb network structure, a sinusoidal network structure or a diamond truss network structure, and the non-auxetic structure preferably includes a quadrilateral network structure or a hexagonal network structure. In the present invention, the geometric structure of each fiber layer in the micron fiber network scaffold layer is as follows: Figure 2 As shown, Figure 2 (a) is a tensile structure (recessed angle honeycomb network structure, sinusoidal network structure, diamond truss network structure), (b) is a non-tensile structure (quadrilateral network structure, hexagonal network structure). Figure 2The local enlarged images in each of the small images are structural units of the corresponding network structure, where w, h and s are fiber spacings, i is the fiber angle, w and h are preferably 200-1000 μm, s is preferably 200-500 μm, i is preferably 30°, 45° or 60°, the amplitude in the sinusoidal structure is preferably 100-500 μm, and w and h in the sinusoidal structure are the distances between adjacent intersections; by regulating w and h, the fiber network scaffold can be given anisotropic characteristics, and the anisotropic ratio (i.e., anisotropic stiffness ratio, the ratio of Young's modulus of the scaffold in the transverse and longitudinal directions) is preferably 1-3. In the present invention, the tensile structure has a negative Poisson's ratio, which can adapt to the volume deformation of dynamic organs (such as heart, stomach, lungs, etc.), and can be given anisotropic characteristics by adjusting the fiber spacing; and the non-tensile structure can be adapted to tissues such as diaphragm and tendons.

[0027] In natural tissues, the fiber network structure in the extracellular matrix (ECM) is orderly arranged to provide mechanical strength and elasticity to the tissue. The hydrogel fiber composite membrane with a "sandwich" structure provided by the present invention has a micron fiber network scaffold as the middle layer (i.e., a micron fiber network scaffold layer), and the fiber diameter (1 to 10 μm) can replicate the diameter and structure of the fiber network in the ECM of natural tissues; the mechanical scalability of the fiber network scaffold can be improved by designing the geometric structural unit of the scaffold to be anisotropic and / or tensile structure; the mechanical strength of the micron fiber network scaffold can be improved by reducing the fiber spacing in the scaffold structure and increasing the number of fiber layers. Therefore, the micron fiber network scaffold layer can maintain mechanical strength and flexibility, thereby replicating the mechanical strength and nonlinear mechanical elasticity of natural tissues, so that it can be personalized to adapt to the biomechanical properties of dynamic organs, which is conducive to better integration of the composite fiber membrane with natural tissues.

[0028] The adhesive hydrogel fiber composite membrane provided by the present invention includes an electrospun nanofiber membrane layer deposited on both sides of the micron fiber network support layer and in the pore structure, and at least the electrospun nanofiber membrane layer on one side of the micron fiber network support layer is loaded with porous self-gelling powder (in some applications, only one side of the surface needs to be adhesive, so only the electrospun nanofiber membrane layer on one side of the micron fiber network support layer needs to be loaded with porous self-gelling powder). In the present invention, the fiber of the electrospun nanofiber membrane layer is polycaprolactone fiber; the thickness of the electrospun nanofiber membrane layer is preferably 50 to 200 μm, specifically 50, 100, 150, 200 μm; the fiber diameter of the electrospun nanofiber membrane layer is preferably 500 nm to 1 μm, specifically 500 nm, 600 nm, 700 nm, 800 nm, 900 nm or 1 μm.

[0029] In the present invention, the porous self-gel powder is obtained by freeze-drying and pulverizing the hydrogel, and the average particle size of the porous self-gel powder is preferably 1 to 10 μm. In the present invention, the porous self-gel powder is preferably a composite gel powder formed by polyacrylic acid (PAA) and polyethyleneimine (PEI), and the mass ratio of PAA to PEI is preferably 1:1. In the present invention, the preparation method of the porous self-gel powder preferably includes the following steps:

[0030] A PEI aqueous solution (PEI molecular weight Mw, ca. 70,000) and a PAA aqueous solution (PAA molecular weight Mw, ca. 240,000) were mixed to obtain a PEI / PAA hydrogel;

[0031] The PEI / PAA hydrogel was immediately immersed in liquid nitrogen for about 15 minutes without pouring out any liquid, and freeze-dried to remove water to obtain a solid;

[0032] The solid is ground to obtain the porous self-gel powder.

[0033] In the present invention, the mass fraction of the PEI aqueous solution is preferably 10%, the mass fraction of the PAA aqueous solution is preferably 10%, and the volume ratio of the PEI aqueous solution to the PAA aqueous solution is preferably 1: 1. In the present invention, the two polymers PEI and PAA are cross-linked through strong non-covalent interactions (such as electrostatic interactions and hydrogen bonds) to form a dense polyelectrolyte-rich gel-like complex, which is freeze-dried and ground to obtain a self-gel powder.

[0034] In the present invention, the mass content of the porous self-gel powder in the electrospun nanofiber membrane layer loaded with the porous self-gel powder is preferably 50 to 80%.

[0035] In the present invention, at least one side surface of the micron fiber network support layer ( Figure 1 As shown, an electrospun nanofiber membrane loaded with porous self-gelling powder (i.e., the electrospun nanofiber membrane layer) is used in the upper and lower layers of the micron fiber network scaffold layer. Due to the strong physical interaction between PEI and PAA polymers and the diffusion of free polymers, PEI / PAA powder can quickly absorb the interfacial water on the tissue surface and quickly form a physically cross-linked hydrogel layer in situ without the need for additional cross-linking agents. At the same time, the physically cross-linked PEI / PAA polymer can diffuse into the polymer network of wet tissue, and the carboxylic acid and amine groups in the PEI / PAA hydrogel can form physical interactions with functional groups (such as amines and thiol groups) on the surface of wet tissue to further enhance tissue adhesion.

[0036] The micro-nano fiber membrane has excellent mechanical properties, high porosity and biomimetic extracellular matrix structure, and can be used to enhance the mechanical properties of hydrogel adhesives. Combining self-gel powder with electrospun nanofiber membrane can enhance the mechanical strength of hydrogel adhesives, but the mechanical properties of the single-layer fiber membrane will decrease with the increase of the content of self-gel powder, and the dense electrospun fiber membrane has poor mechanical elasticity and cannot adapt to the nonlinear mechanical elasticity of natural soft tissues and the tensile expansion structure required for dynamic organ volume deformation. The present invention combines the strong wet tissue adhesion of self-gel powder with the adjustable mechanical properties of micro-nano fiber scaffolds to provide a hydrogel fiber composite membrane with a "sandwich" structure. After the electrospun nanofiber membrane layer on the surface contacts with biological tissues and absorbs interfacial water, it quickly gels in situ to form a hydrogel layer to achieve strong tissue adhesion. At the same time, the micron fiber scaffold in the middle layer is designed with an adjustable anisotropic-tensile expansion structure, which can adapt to the biomechanical characteristics of a wide range of dynamic organs (including anisotropic mechanical strength and nonlinear mechanical elasticity), so that the composite membrane can simultaneously meet the strong adhesion of wet tissues and adapt to the biomechanical properties of dynamic organs.

[0037] The present invention provides a method for preparing an adhesive hydrogel fiber composite membrane adapted to dynamic organ mechanical properties as described in the above technical solution, comprising the following steps:

[0038] The polycaprolactone was subjected to MEW printing to obtain a micron fiber network scaffold layer;

[0039] dissolving polycaprolactone in an organic solvent to obtain a spinning solution;

[0040] The spinning solution is used to electrospin the two side surfaces of the micron fiber network scaffold layer and spray porous self-gel powder respectively to obtain the adhesive hydrogel fiber composite membrane adapted to the dynamic organ mechanical properties; the spraying of porous self-gel powder is carried out at least during the process of electrospinning one side surface of the micron fiber network scaffold layer.

[0041] The present invention performs MEW printing (melt direct writing technology) on polycaprolactone to obtain a micron fiber network support layer. In the present invention, the weight average molecular weight of the polycaprolactone (PCL) is preferably 450,000 to 650,000. In the present invention, the conditions of the MEW printing preferably include: heating polycaprolactone to form a polycaprolactone melt, the pumping pressure of the polycaprolactone melt is 0.2 to 1 bar, the distance from the print head to the receiving plate is 3 to 4 mm, the applied voltage is 3 to 5 kV, and the printing speed (i.e., the moving speed of the receiving plate) is 1000 to 1500 mm / min. In the present invention, the heating temperature is preferably 80 to 90°C; the pumping pressure of the polycaprolactone melt is preferably controlled by an air pump, and the flow rate of the polycaprolactone melt is controlled by controlling the pumping pressure of the polycaprolactone melt; the diameter of the print head can be selected to be 0.3 mm or less, mainly by adjusting the process parameters to change the fiber diameter.

[0042] The present invention dissolves polycaprolactone in an organic solvent to obtain a spinning solution. In the present invention, the weight average molecular weight of the polycaprolactone is preferably 800,000 to 1,000,000, and the organic solvent is preferably acetone; the concentration of the spinning solution is preferably 10 to 12% w / v, specifically 10%, 11%, 12% w / v (Note: 12% w / v means that the solute is 12g per 100 ml of solution).

[0043] After obtaining the micron fiber network scaffold layer and the spinning solution, the present invention uses the spinning solution to electrospin and spray porous self-gel powder on the two side surfaces of the micron fiber network scaffold layer respectively to obtain the adhesive hydrogel fiber composite membrane adapted to the dynamic organ mechanical properties; the spraying of porous self-gel powder is carried out at least during the process of electrospinning one side surface of the micron fiber network scaffold layer.

[0044] In the present invention, the specific operation of electrospinning the spinning solution on both sides of the micron fiber network support layer is: electrospinning one side of the micron fiber network support layer, and then turning the micron fiber network support layer over, and using the other side as the receiving surface for electrospinning fibers. In the present invention, the conditions for electrospinning preferably include: the flow rate of the spinning solution is 0.8-1 mL / h, the distance from the spinning needle to the receiving plate is 15-20 cm, the spinning voltage is 15-20 kV, the micron fiber network support layer is placed between the spinning needle and the receiving plate, and the distance between the micron fiber network support layer and the receiving plate is 5-10 cm. In the present invention, the spinning needle is preferably a needle with a specification of 21G, and the thickness of the electrospun nanofiber membrane layer is controlled by the spinning time. In the present invention, the porous self-gel powder is preferably sprayed by a blower, and the sprayed self-gel powder and the nanofibers (the denser electrospun nanofibers as carriers) are firmly, evenly and stably combined in the electrospinning path (in the air) by electrostatic adsorption, and finally deposited and wound on the micron fiber network support to form a "sandwich" structure hydrogel fiber composite membrane. In the present invention, the loading amount of the porous self-gel powder in the nanofiber is controlled by adjusting the jet air flow velocity (10 to 30 kPa) of the porous self-gel powder; the electrospun nanofibers can pass through the micron fiber network support layer to wrap around and cover its surface.

[0045] The present invention provides the use of the adhesive hydrogel fiber composite membrane adapted to the mechanical properties of dynamic organs as described in the above technical solution or the adhesive hydrogel fiber composite membrane adapted to the mechanical properties of dynamic organs prepared by the preparation method described in the above technical solution in the preparation of tissue repair and / or regeneration materials, dynamic wound sealing materials, hemostatic and antibacterial materials and drug delivery materials. The hydrogel fiber composite membrane provided by the present invention can simultaneously meet the strong adhesion of wet tissues and the biomechanical properties adapted to dynamic organs, and has broad application prospects in the fields of tissue repair and regeneration, dynamic wound sealing, hemostatic and antibacterial materials and drug delivery. The present invention has no special requirements for the method of application, and the application method familiar to those skilled in the art can be used.

[0046] To further illustrate the present invention, the adhesive hydrogel fiber composite membrane adapted to dynamic organ mechanical properties and its preparation method and application provided by the present invention are described in detail below in conjunction with examples, but they should not be construed as limiting the scope of protection of the present invention.

[0047] Example 1

[0048] The preparation of the adhesive hydrogel fiber composite membrane adapted to the dynamic organ mechanical properties is as follows:

[0049] (1) Preparation of porous self-gel powder (polyacrylic acid (PAA) and polyethyleneimine (PEI) composite gel, denoted as PAA / PEI porous self-gel powder)

[0050] Equal volumes of PEI aqueous solution (molecular weight Mw, ca. 70000; mass fraction 10%) and PAA aqueous solution (Mw, ca. 240,000; mass fraction 10wt%) were mixed, and the formed PEI / PAA composite gel was immediately immersed in liquid nitrogen for about 15 minutes without pouring out any liquid, and freeze-dried to remove moisture; finally, the dried solid was ground to obtain PAA / PEI self-gel powder with a particle size of 1 to 10 μm.

[0051] (2) Hydrogel fiber composite membrane ( Figure 1 As shown) and its preparation

[0052] This embodiment provides a "sandwich" structure hydrogel fiber composite membrane, which is composed of a fiber network support 1 in the middle layer, and an electrospun nanofiber membrane 2 loaded with porous self-gel powder in the upper and lower layers. The geometric structure of the fiber network support 1 is a tensile expansion structure - a sinusoidal network structure (such as Figure 2 shown).

[0053] The preparation of the hydrogel fiber composite membrane is as follows:

[0054] The melt direct writing technology MEW was used to print the micron fiber network scaffold 1. The printing process parameters were as follows: the melted polycaprolactone (PCL, molecular weight Mw 450000) was heated at a constant temperature of 90°C, the flow rate of the melted PCL was controlled by an air pump, the pump pressure was set to 0.2 bar, the distance from the print head to the receiving plate was 4 mm, the applied voltage was 3.5 kV, the printing speed (receiving plate moving speed) was 1000 mm / min, and a sinusoidal structure MEW micron fiber network scaffold (fiber diameter 10 μm, fiber spacing w (short axis direction) 400 μm, fiber spacing h (long axis direction) 800 μm, amplitude 100 μm, and fiber layer number 5) was obtained;

[0055] Dissolve polycaprolactone powder (molecular weight Mw 800000) in acetone solution to prepare a 10% w / v spinning solution;

[0056] The fiber network support 1 is placed between the electrospinning needle and the receiving plate, the distance between the micron fiber network support layer and the receiving plate is 5 cm, and the nanofiber membrane 2 loaded with porous self-gel powder is collected. The electrospinning process conditions are as follows: the spinning solution flow rate is 1 mL / h, the distance from the spinning needle to the receiving plate is 20 cm, the spinning voltage is 20 kV, the PAA / PEI porous self-gel powder (prepared in step (1) of Example 1) is ejected by a blower, and is firmly and evenly combined with the PCL nanofibers in the air through electrostatic adsorption in the electrospinning path. The loading amount of the porous self-gel powder is controlled by adjusting the powder injection air flow velocity (10-30 kPa), and then deposited and wound on the micron fiber support 1 together, finally forming a hydrogel composite fiber membrane with a "sandwich" structure. The thickness of the electrospun nanofiber membrane 2 is 50-200 μm, the fiber diameter is 500 nm-1 μm, and the mass content of the porous self-gel powder in the electrospinning nanofiber membrane layer is 50-80%.

[0057] Figure 3 This is a scanning electron microscope image of the MEW micron fiber network scaffold with a sinusoidal structure in Example 1.

[0058] The stress-strain curves of the MEW micron fiber network scaffold in Example 1 along the long axis and short axis were tested by uniaxial tensile test using a tensile tester (Instron 5944). Figure 4 As shown, the micron fiber network scaffold exhibits a J-type stress-strain response similar to that of natural soft tissue. Line fitting was performed on the elastic region of the stress-strain curve of the sample, and the Young's modulus E1 in the long axis direction was calculated to be 1.00 MPa, the Young's modulus E2 in the short axis direction was 0.47 MPa, and the anisotropic modulus ratio E1 / E2 of the scaffold was 2.13.

[0059] Example 2

[0060] The MEW micron fiber network support with a sinusoidal structure in Example 1 was replaced with a micron fiber network support with the following structure, and the rest was the same as Example 1:

[0061] The fiber network support 1 has a support geometry of a tensile structure (a concave angle honeycomb network structure or a diamond truss network structure) or a non-tensile structure (a quadrilateral network structure or a hexagonal network structure) (e.g. Figure 2 As shown), the fiber diameter is 1 to 10 μm, the number of fiber printing layers is 1 to 50, the fiber spacing w and h are 200 to 1000 μm respectively, the fiber spacing s is 200 to 500 μm, and the fiber angle i is 30°, 45° or 60°.

[0062] After the "sandwich" structure hydrogel fiber composite membrane provided by the present invention contacts biological tissue and absorbs interfacial water, it quickly gels in situ to form a hydrogel layer, achieving strong tissue adhesion, while the micron fiber scaffold in the middle layer maintains mechanical strength and nonlinear mechanical elasticity. The hydrogel fiber composite membrane provided by the present invention can simultaneously meet the strong adhesion of wet tissue and adapt to the biomechanical properties of dynamic organs.

[0063] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be regarded as the protection scope of the present invention.

Claims

1. An adhesive hydrogel fiber composite membrane adapted to the mechanical properties of dynamic organs, comprising a micron fiber network scaffold layer, an electrospun nanofiber membrane layer deposited on both side surfaces and in the pore structure of the micron fiber network scaffold layer, at least the electrospun nanofiber membrane layer on one side of the micron fiber network scaffold layer is loaded with porous self-gelling powder; the fibers of the micron fiber network scaffold layer and the electrospun nanofiber membrane layer are both polycaprolactone fibers.

2. The adhesive hydrogel fiber composite membrane adapted to dynamic organ mechanical properties according to claim 1, characterized in that: The fiber diameter of the micron fiber network support layer is 1 to 10 μm, and the number of fiber layers is 1 to 50.

3. The adhesive hydrogel fiber composite membrane adapted to dynamic organ mechanical properties according to claim 2, characterized in that: The geometric structure of each fiber layer in the micron fiber network scaffold layer includes an auxetic structure or a non-auxetic structure. The auxetic structure includes a concave angle honeycomb network structure, a sinusoidal network structure or a diamond truss network structure. The non-auxetic structure includes a quadrilateral network structure or a hexagonal network structure.

4. The adhesive hydrogel fiber composite membrane adapted to dynamic organ mechanical properties according to claim 1, characterized in that: The thickness of the electrospun nanofiber membrane layer is 50-200 μm; the fiber diameter of the electrospun nanofiber membrane layer is 500 nm-1 μm.

5. The adhesive hydrogel fiber composite membrane adapted to dynamic organ mechanical properties according to claim 1, characterized in that: The average particle size of the porous self-gel powder is 1-10 μm, and the porous self-gel powder is a composite gel powder formed by polyacrylic acid and polyethylene imine.

6. The adhesive hydrogel fiber composite membrane adapted to dynamic organ mechanical properties according to claim 1 or 5, characterized in that: The mass content of the porous self-gel powder in the electrospun nanofiber membrane layer loaded with the porous self-gel powder is 50-80%.

7. The method for preparing the adhesive hydrogel fiber composite membrane adapted to the dynamic organ mechanical properties according to any one of claims 1 to 6, characterized in that: The following steps are involved: The polycaprolactone was subjected to MEW printing to obtain a micron fiber network scaffold layer; dissolving polycaprolactone in an organic solvent to obtain a spinning solution; The spinning solution is used to electrospin the two side surfaces of the micron fiber network scaffold layer and spray porous self-gel powder respectively to obtain the adhesive hydrogel fiber composite membrane adapted to the dynamic organ mechanical properties; the spraying of porous self-gel powder is carried out at least during the process of electrospinning one side surface of the micron fiber network scaffold layer.

8. The preparation method according to claim 7, characterized in that: The MEW printing conditions include: heating polycaprolactone to form a polycaprolactone melt, the pumping pressure of the polycaprolactone melt is 0.2-1 bar, the distance from the print head to the receiving plate is 3-4 mm, the applied voltage is 3-5 kV, and the printing speed is 1000-1500 mm / min.

9. The preparation method according to claim 7, characterized in that: The concentration of the spinning solution is 10-12% w / v, and the conditions for the electrospinning include: the flow rate of the spinning solution is 0.8-1 mL / h, the distance from the spinning needle to the receiving plate is 15-20 cm, the spinning voltage is 15-20 kV, the micron fiber network support layer is placed between the spinning needle and the receiving plate, and the distance between the micron fiber network support layer and the receiving plate is 5-10 cm.

10. Use of the adhesive hydrogel fiber composite membrane adapted to the dynamic mechanical properties of organs as described in any one of claims 1 to 6 or the adhesive hydrogel fiber composite membrane adapted to the dynamic mechanical properties of organs prepared by the preparation method described in any one of claims 7 to 9 in the preparation of tissue repair and / or regeneration materials, dynamic wound sealing materials, hemostatic and antibacterial materials and drug delivery materials.

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