Collagen membrane with function of inducing ordered remodeling of tissues as well as preparation method and application of collagen membrane

Abstract

The invention belongs to the technical field of surgical article materials, and particularly relates to a collagen membrane with an effect of inducing ordered remodeling of tissues as well as a preparation method and application of the collagen membrane. The collagen membrane is obtained by performing hot pressing treatment on a fiber membrane; the fiber membrane is formed by crossing and laminating fibers with the diameter of 0.5-15 microns; the fiber comprises collagen and poly (L-lactide-caprolactone), and the mass ratio of the collagen to the poly (L-lactide-caprolactone) is 1: (1.5-2.5). The collagen membrane provided by the invention combines collagen with good biocompatibility and a tissue repair promoting effect with biodegradable PLCL with excellent mechanical properties and good cell adhesion, not only has an extracellular matrix-like structure, but also has good structural stability, is beneficial to regulation of cell behaviors and tissue regeneration, and can be used for preparing the collagen membrane. The growth, adhesion and proliferation of host cells can be effectively promoted, so that ordered remodeling of tissues is induced.

Description

Technical Field

[0001] The present invention relates to the technical field of surgical supplies materials, and more specifically, to a collagen membrane with the function of inducing orderly tissue remodeling, a preparation method thereof, and an application thereof. Background Art

[0002] Tendon and ligament problems are currently the most common musculoskeletal diseases. Tendons and ligaments (T / L) are composed of dense connective tissues, which transmit forces between muscles and bones, and between bones respectively, thereby allowing joint movement and force exertion, and playing an important role in the normal movement and stability of joints. When T / L is damaged, the continuity of the damaged tendon is mainly restored by surgical intervention methods. Specific methods include direct suture, autologous tendon transplantation, artificial tendon transplantation, etc. However, the long-term clinical effects of these methods are not good, and there are many adverse reactions, such as retear, adhesion formation, scar formation, and joint stiffness, etc.

[0003] In view of the above problems, a tissue engineering scaffold prepared from tissue remodeling biomaterials has been developed, which can induce trauma tissue remodeling, repair, and regeneration by regulating the growth and differentiation of cells around the trauma, promoting the regeneration of blood vessels and nerves, and the connection with surrounding tissues. For example, the prior art discloses a ligament regeneration scaffold with a layer-by-layer induction performance and a preparation method thereof. The ligament regeneration scaffold has a multi-layer composite structure, which is composed of a gradient-degrading microfiber reinforcement layer and an oriented nanofiber induction layer overlapping and compounding. The microfiber reinforcement layer is woven by yarns with different degradation cycles through multi-dimensional and multi-layer textile molding. The nanofiber induction layer is prepared by electrospinning of a polymer material and a bioactive component; by regulating the gradient-degrading structure, while ensuring the initial mechanical strength, the gradient degradation of the microfiber reinforcement layer is realized, and the nanofiber induction layer is exposed layer by layer, thereby improving the infiltration performance of the internal tissue of the scaffold to increase the cell penetration depth inside the scaffold, but the structural stability of its nanofiber induction layer is poor. Summary of the Invention

[0004] The purpose of the present invention is to overcome the defects or deficiencies of the existing ligament regeneration scaffold with poor dimensional stability after swelling, and to provide a collagen membrane with the function of inducing orderly tissue remodeling.

[0005] Another purpose of the present invention is a preparation method of the above-mentioned collagen membrane with the function of inducing orderly tissue remodeling.

[0006] Another purpose of the present invention is the application of the above-mentioned collagen membrane in the preparation of a tissue regeneration membrane.

[0007] The above purposes of the present invention are achieved by the following technical solutions:

[0008] The present invention protects a collagen membrane with the function of inducing orderly tissue remodeling, which is obtained by hot pressing a fibrous membrane;

[0009] The fibrous membrane is formed by cross - laminating fibers with an average diameter of 0.5 - 15 μm;

[0010] The fibers include collagen and poly(L - lactide - co - caprolactone), and the mass ratio of collagen to poly(L - lactide - co - caprolactone) is 1:(1.5 - 2.5).

[0011] The present invention selects fibers with a specific diameter to ensure that the fiber diameter in the finally obtained collagen membrane is relatively similar to the collagen fiber diameter in the tendon extracellular matrix. The formed extracellular matrix - like structure is beneficial to regulating cell behavior and tissue regeneration, and can provide a favorable regeneration environment for the growth, adhesion and proliferation of host cells, thus being conducive to inducing orderly tissue remodeling.

[0012] Moreover, the fibers contain collagen with good biocompatibility and the biodegradable polymer poly(L - lactide - co - caprolactone) (PLCL), which can endow the collagen membrane with excellent mechanical properties. At the same time, through research, it is found that the ratio of the two has a key role in the stability of the overall structure of the collagen membrane. When the addition amount of poly(L - lactide - co - caprolactone) is too large, the change in fiber diameter before and after the collagen membrane is soaked in PBS buffer solution is large, resulting in poor overall structural stability of the collagen membrane; when the addition amount of poly(L - lactide - co - caprolactone) is too small, the fiber morphology cannot be observed after the collagen membrane is soaked in PBS buffer solution, which is not conducive to inducing orderly tissue remodeling.

[0013] The purpose of the hot pressing treatment is to reduce the voids between the fibrous membranes, and at the same time, under the action of temperature and pressure, a certain degree of connection occurs at the contact points between different fibers, changing the loose fiber stacking state of the original fibrous membrane, thereby improving the mechanical properties of the collagen membrane. The temperature of the hot pressing treatment is based on ensuring that the collagen does not denature; the pressure of the hot pressing treatment has an important influence on the thickness of the collagen membrane, and can be selected according to the actual requirements of different collagen membranes.

[0014] The above - mentioned collagen can be one or several of bovine tendon - derived, porcine dermis - derived, fish skin - derived and small intestine - derived; in the poly(L - lactide - co - caprolactone) (PLCL), LA:CL=(15 - 30):(70 - 85) (molar ratio); optionally, the molecular weight Mw of the poly(L - lactide - co - caprolactone) is 140000 - 180000, for example, the molecular weight Mw = 161000.

[0015] Preferably, the mass ratio of the collagen to the poly(L - lactide - co - caprolactone) is 1:(1.8 - 2.2). More preferably, the mass ratio of the collagen to the poly(L - lactide - co - caprolactone) is 1:2.

[0016] Specifically, the average thickness of the fiber membrane is 50 - 300 μm. The thickness of the fiber membrane affects the thickness of the collagen membrane after hot pressing treatment, and further affects the repair effect of the collagen membrane.

[0017] Optionally, the average thickness of the fiber membrane is 135 - 289 μm, 147 μm, 176 μm, 182 μm or 203 μm.

[0018] In a specific embodiment, the temperature of the hot pressing treatment is 40 - 48 °C, the time is 15 - 40 min; the pressure of the hot pressing treatment is 100 - 160 Pa. Optionally, the temperature is 40 - 44 °C, the time is 20 - 30 min; the temperature is 40 °C, the time is 30 min; the temperature is 42 °C, the time is 25 min; the temperature is 44 °C, the time is 20 min.

[0019] Specifically, the specific operation of the hot pressing treatment is: under the conditions of 40 - 48 °C and 100 - 160 Pa, use frosted glass to press on the fiber membrane and maintain for 15 - 40 min.

[0020] The temperature of the hot pressing treatment has a greater impact on the performance of the collagen membrane. Different temperatures will change the molecular chain movement state inside poly(L-lactide-co-caprolactone) and the state of collagen (whether denaturation occurs); when the temperature of the hot pressing treatment is 40 - 48 °C, the hot pressing effect can be better guaranteed, and the collagen membrane has more excellent mechanical properties. Specifically, the fiber membrane is prepared by electrospinning of a spinning solution.

[0021] The present invention also protects a preparation method of a collagen membrane, including the following steps:

[0022] S1. Prepare a fiber membrane by electrospinning a spinning solution;

[0023] S2. Perform hot pressing treatment on the fiber membrane in S1 to obtain a collagen membrane;

[0024] Among them, the spinning solution for electrospinning in S1 includes collagen and poly(L-lactide-co-caprolactone).

[0025] It should also be noted that: after the above hot pressing treatment, it may also include vacuum drying and sterilization treatment; specifically, the vacuum pressure for vacuum drying is 5 - 15 kPa, and the number of cycles is 3 - 7 times; the sterilization treatment can use irradiation sterilization; it may also include cutting, cutting the formed collagen membrane into a suitable size.

[0026] Specifically, the spinning solution is composed of collagen, poly(L-lactide-co-caprolactone), hexafluoroisopropanol, acetic acid and water. Among them, collagen with good biocompatibility and the biodegradable polymer poly(L-lactide-co-caprolactone) (PLCL) are used as the main components, acetic acid and the highly polar solvent hexafluoroisopropanol are used as auxiliary components, and an appropriate amount of water is added simultaneously to form a spinning solution with clear solution, uniform dispersion and no visible impurities to the naked eye.

[0027] Specifically, the mass ratio of collagen to poly(L-lactide-co-caprolactone) in the spinning solution is 1:(1.5 - 2.5); the mass concentration of collagen is 5 - 10 g / mL, the mass concentration of poly(L-lactide-co-caprolactone) is 10 - 20 g / mL, the volume concentration of hexafluoroisopropanol is 90% - 98%, and the volume concentration of acetic acid is 1% - 5%. Among them, the mass concentration of collagen (g / mL) = mass of collagen / volume of solvent * 100%;

[0028] The mass concentration of PLCL (g / mL) = mass of PLCL / volume of solvent * 100%.

[0029] The specific operation of electrospinning is as follows:

[0030] Add the above spinning solution into a syringe and connect a spinneret. Use a roller as the receiving device and a syringe pump as the propulsion device. Prepare a fiber membrane by high-voltage spinning onto the roller, and make the surface of the fiber membrane flat, smooth and free of visible impurities to the naked eye. Optionally, the voltage of electrospinning is 25 - 40 kV, the propulsion rate is 10 - 30 μL / min, and the distance between the spinneret and the roller is 15 - 30 cm. The spinning time can be controlled by controlling the total amount of the spinning solution, and further the thickness of the fiber membrane can be controlled.

[0031] The application of a collagen membrane with the above-mentioned function of inducing orderly tissue remodeling in the preparation of a tissue regeneration membrane is also within the protection scope of the present invention.

[0032] The present invention has the following beneficial effects:

[0033] The collagen membrane of the present invention combines collagen with good biocompatibility and tissue repair promotion function and the biodegradable polymer poly(L-lactide-co-caprolactone) with excellent mechanical properties and good cell adhesion. It not only has an extracellular matrix-like structure but also has good structural stability, which is beneficial to regulating cell behavior and tissue regeneration, can effectively promote the growth, adhesion and proliferation of host cells, and thus induce the orderly remodeling of tissues. Description of the Drawings

[0034] Figure 1 It is the scanning electron microscope (SEM) images of the collagen membrane of the present invention at different magnifications.

[0035] Figure 2 Scanning electron microscope (SEM) images of the collagen membranes before and after immersion in PBS buffer solution in Example 3 and Comparative Examples 1-2.

[0036] Figure 3 Graph of the change in fiber diameter of the collagen membranes before and after immersion in PBS buffer solution in Example 3 and Comparative Examples 1-2.

[0037] Figure 4 Graph of the in vitro cytotoxicity experiment of the collagen membranes in Example 3 and Comparative Examples 1-2. Detailed implementation manners

[0038] The technical solutions in the present application will be clearly and completely described below.

[0039] The present invention provides a collagen membrane with the function of inducing orderly tissue remodeling. The collagen membrane is obtained by hot pressing a fiber membrane; the fiber membrane is formed by cross-laminating fibers with an average diameter of 0.5-15 μm. The fibers include collagen and poly(L-lactide-co-caprolactone).

[0040] In some embodiments of the present invention, the mass ratio of collagen to poly(L-lactide-co-caprolactone) is 1:(1.5-2.5). Specifically, the mass ratio of collagen to poly(L-lactide-co-caprolactone) is 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2.0, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5. By selecting fibers with a specific diameter in the present invention, it can be ensured that the fiber diameter in the finally obtained collagen membrane is relatively similar to the collagen fiber diameter in the tendon extracellular matrix. The formed extracellular matrix-like structure is beneficial to regulating cell behavior and tissue regeneration, and can provide a favorable regeneration environment for the growth, adhesion and proliferation of host cells, thereby being beneficial to inducing orderly tissue remodeling.

[0041] In some embodiments of the present invention, the average thickness of the fiber membrane is 50-300 μm. Further, the average thickness of the fiber membrane is 135-289 μm. Specifically, the average thickness of the fiber membrane is 135 μm, 140 μm, 145 μm, 147 μm, 160 μm, 170 μm, 176 μm, 182 μm, 190 μm, 203 μm, 210 μm, 220 μm, 230 μm, 240 μm, 250 μm, 260 μm, 270 μm, 280 μm, 289 μm. The thickness of the fiber membrane will affect the thickness of the collagen membrane after hot pressing, and thus affect the repair effect of the collagen membrane.

[0042] In some embodiments of the present invention, the temperature of the hot pressing treatment is 40-48 °C, and further can be 40-44 °C. For example, 40 °C, 41 °C, 42 °C, 43 °C, 44 °C, 45 °C, 46 °C, 47 °C, 48 °C.

[0043] In some embodiments of the present invention, the time of the hot pressing treatment is 15-40 min, and further can be 20-30 min. For example, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min.

[0044] In some embodiments of the present invention, the pressure of the hot pressing treatment is 100-160 Pa.

[0045] The present invention also protects a method for preparing a collagen membrane, comprising the following steps:

[0046] S1. Preparing a fibrous membrane by electrospinning a spinning solution;

[0047] S2. Subjecting the fibrous membrane in S1 to a hot pressing treatment to obtain a collagen membrane;

[0048] Among them, the spinning solution for electrospinning in S1 comprises collagen and poly(L-lactide-co-caprolactone).

[0049] In some embodiments of the present invention, the mass concentration of collagen is 5-10 g / mL. For example, 5 g / mL, 6 g / mL, 7 g / mL, 8 g / mL, 9 g / mL, 10 g / mL.

[0050] In some embodiments of the present invention, the mass concentration of poly(L-lactide-co-caprolactone) is 10-20 g / mL. For example, 10 g / mL, 11 g / mL, 12 g / mL, 13 g / mL, 14 g / mL, 15 g / mL, 16 g / mL, 17 g / mL, 18 g / mL, 19 g / mL, 20 g / mL.

[0051] In some embodiments of the present invention, the volume concentration of hexafluoroisopropanol is 90%-98%. For example, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%.

[0052] In some embodiments of the present invention, the volume concentration of acetic acid is 1%-5%. For example, 1%, 2%, 3%, 4%, 5%.

[0053] The specific operation of electrospinning is as follows:

[0054] Adding the above spinning solution into a syringe and connecting a spinneret, using a roller as a receiving device and a peristaltic pump as a propulsion device, spinning onto the roller under high pressure to prepare a fibrous membrane, and making the surface of the fibrous membrane flat, smooth, and free of impurities visible to the naked eye, etc.

[0055] In some embodiments of the present invention, the voltage for electrospinning is 25 - 40 kV. For example, 25 - 30 kV, 30 - 35 kV, 35 - 40 kV

[0056] In some embodiments of the present invention, the advancing rate is 10 - 30 μL / min. For example, 10 μL / min, 15 μL / min, 20 μL / min, 25 μL / min, 30 μL / min.

[0057] In some embodiments of the present invention, the distance between the spinneret and the roller is 15 - 30 cm. For example, 15 cm, 20 cm, 25 cm, 30 cm.

[0058] The collagen membrane of the present invention not only has an extracellular matrix-like structure, but also has good structural stability, which is beneficial to regulating cell behavior and tissue regeneration, can effectively promote the growth, adhesion and proliferation of host cells, and thus induce the orderly remodeling of tissues.

[0059] The embodiments of the present invention will be described in detail below with reference to the accompanying drawings of the specification and specific examples. The described embodiments are only a part of the embodiments of the present application, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present application without creative work fall within the scope of protection of the present application.

[0060] Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the technical field, and all reagents and materials are commercially available.

[0061] The collagen is derived from bovine tendon, the manufacturer is Guangzhou Chuang'er Biotechnology Co., Ltd., and the name is type I collagen powder;

[0062] Poly(L-lactide-co-caprolactone) 1, molecular weight Mw = 161000, LA:CL = 70:30, the manufacturer is Evonik Degussa (Shanghai) Co., Ltd., and the grade is LC703S;

[0063] Poly(L-lactide-co-caprolactone) 2, LA:CL = 85:15, the manufacturer is Corbion-Purac, and the grade is PLC 8516.

[0064] Examples 1 - 6

[0065] A collagen membrane with the function of inducing the orderly remodeling of tissues is prepared by the following preparation method:

[0066] S1. Electrospinning: Add the spinning solution (40 mL) into a syringe and connect the spinneret. Use a roller as the receiving device and a syringe pump as the propulsion device to obtain a fibrous membrane.

[0067] S2. Hot pressing treatment: Subject the fibrous membrane obtained in S1 to hot pressing treatment to obtain a collagen membrane with the function of inducing orderly tissue remodeling.

[0068] The specific parameters of the spinning solution, electrospinning parameters in step S1 and the hot pressing treatment in step S2 are shown in Table 1.

[0069] Use a digital thickness gauge to measure the thickness at 5 points of the collagen membrane at equal intervals, and calculate the average thickness of the collagen membrane; Observe the fiber morphology of the collagen membrane by SEM, randomly select 10 fibers, measure their fiber diameters using Nano Measure, and calculate the average fiber diameter. The results are shown in Table 1.

[0070] Comparative Examples 1 - 2

[0071] A collagen membrane is prepared by the following preparation method:

[0072] S1. Electrospinning: Add the spinning solution (40 mL) into a syringe and connect the spinneret. Use a roller as the receiving device and a syringe pump as the propulsion device to obtain a fibrous membrane.

[0073] S2. Hot pressing treatment: Subject the fibrous membrane obtained in S1 to hot pressing treatment to obtain a collagen membrane with the function of inducing orderly tissue remodeling.

[0074] The specific parameters of the spinning solution, electrospinning parameters in step S1 and the hot pressing treatment in step S2 are shown in Table 1.

[0075] Use a digital thickness gauge to measure the thickness at 5 points of the collagen membrane at equal intervals, and calculate the average thickness of the collagen membrane; Observe the fiber morphology of the collagen membrane by SEM, randomly select 10 fibers, measure their fiber diameters using Nano Measure, and calculate the average fiber diameter. The results are shown in Table 1.

[0076] Table 1

[0077]

[0078] Performance testing

[0079] (1) SEM test of the collagen membrane: Specifically refer to ISO 10993 - 19 "Biological evaluation of medical devices - Part 19: Characterization of physical, chemical, morphological and surface properties of materials", and use a cold field emission scanning electron microscope to observe the fiber morphology of the collagen membrane.

[0080] The collagen membranes in Examples 1 - 6 and Comparative Examples 1 - 2 were immersed in PBS buffer solution at 37°C for 24 h, then taken out and dried. Subsequently, SEM was used to observe the fiber morphology of each specimen before and after immersion. Ten fibers were randomly selected and their fiber diameters were measured using Nano Measure, and the average fiber diameter was calculated. The change rate = (average fiber diameter after immersion - average fiber diameter before immersion) / average fiber diameter before immersion * 100%. At the same time, since fiber swelling and shrinkage occurred simultaneously during the immersion process, the change rate was taken as a positive value. The test results are shown in Table 2:

[0081] Table 2

[0082]

[0083] It can be seen from Figure 1 that the collagen membrane of the present invention has an extracellular matrix (ECM)-like microstructure, which can provide a favorable regeneration environment for the growth, adhesion, and proliferation of host cells, thereby inducing the orderly remodeling of tissues.

[0084] It can be seen from Table 2 and Figure 3 that the change rates of the average fiber diameters of the collagen membranes in Examples 1 - 6 after immersion in PBS buffer solution were 6.5% - 10.9%, indicating their excellent structural stability. After the collagen membrane in Comparative Example 1 was immersed, the fibers therein directly dissolved in the PBS buffer solution; the change rate of the average fiber diameter of the collagen membrane in Comparative Example 2 was as high as 59.4%, indicating poor structural stability of the collagen membranes in Comparative Examples 1 and 2.

[0085] At the same time, it can be seen from as Figure 2 that after the collagen membranes in Example 3, Comparative Example 1, and Comparative Example 2 were immersed in PBS buffer solution, when the mass ratio of collagen to PLCL was 1:1, the fibers of the collagen membrane dissolved and the fiber morphology could not be observed; when the mass ratio of collagen to PLCL was 1:3, the fiber diameters of the collagen membrane changed greatly, that is, the performance was unstable; while when the mass ratio of collagen to PLCL was 1:2, the fiber diameter distribution and size of the collagen membrane before and after immersion in PBS buffer solution basically did not change, indicating its stable performance. Therefore, only when the mass ratio of collagen to PLCL is within a suitable range can the structural performance of the collagen fiber membrane be stable.

[0086] (2) Tensile property test: Referring to ASTM D882 - 18 "Standard Test Method for Tensile Properties of Plastic Sheeting", an electric tensile testing machine was used to measure the tensile strength and elongation at break of Example 3 before and after hot pressing.

[0087] The tensile strength calculation formula is σ = F / s, where σ is the tensile strength (MPa), F is the maximum load (N) borne by the specimen at fracture, and s is the cross-sectional area of the specimen (width × thickness, mm 2 ).

[0088] The formula for elongation at break is ε = (ΔL 0 / L) × 100%, where ε is the elongation at break (%), ΔL 0 is the increment of the specimen gauge length (mm), and L is the specimen gauge length (mm).

[0089] Both the fiber membrane before hot pressing and the collagen membrane after hot pressing in Example 3 were cut into a size of 15 mm × 70 mm. The distance between the clamps of the testing machine (specimen gauge length L) was set to 50 mm, and the tensile speed was 500 mm / min. The maximum load F, cross-sectional area s, and increment of the specimen gauge length ΔL borne by the membrane during the testing process were recorded respectively 0 , and the tensile strength σ and elongation at break ε of the fiber membrane before hot pressing and the collagen membrane after hot pressing were calculated according to the formula.

[0090] According to the tensile property test and calculation results, the tensile strength of the fiber membrane before hot pressing in Example 3 was 3.2 MPa, and the elongation at break was 217%; the tensile strength of the collagen membrane after hot pressing in Example 3 was 4.5 MPa, and the elongation at break was 315%. The experimental results show that the collagen membrane prepared by the present invention with the function of inducing orderly tissue remodeling has good mechanical properties both before and after hot pressing; by comparing the experimental data before and after hot pressing, it can be seen that the tensile strength and elongation at break of the collagen membrane increase significantly after hot pressing, showing excellent mechanical properties.

[0091] (3) Cell compatibility test: Referring to ISO 10993-5 "Biological evaluation of medical devices - Part 5: Tests for in vitro cytotoxicity", the CCK-8 and MTT methods were used to observe the effect of the collagen membrane extracts in Example 3, Comparative Example 1, and Comparative Example 2 on the proliferation rate of mouse epithelial-like fibroblasts to test the cell compatibility of the collagen membrane.

[0092] The collagen membranes in Example 3, Comparative Example 1, and Comparative Example 2 were completely immersed in MEM medium for extraction for 72 h, and the extracts were adjusted to 4 volume concentrations (100%, 75%, 50%, and 25%) for testing. Mouse epithelial-like fibroblasts were cultured for 24 h and then mixed with the above-mentioned different concentrations of the extracts to be tested, and the absorption wavelengths were measured by the CKK-8 and MTT methods respectively.

[0093] As Figure 4As shown, this experiment studied the survival of L-929 cells in the extract of the collagen membrane. Compared with the normal control group, the cell survival rates of the negative control group and the positive control group were within the normal range, proving the effectiveness of the experimental results. With the change of the concentration of the collagen membrane extract, the cell proliferation rates were slightly different, but all were greater than 70%. The results showed that the collagen membranes formed in various ratios had no cytotoxicity, preliminarily proving their biocompatibility and safety. The collagen membrane prepared by the present invention, which has the effect of inducing the orderly remodeling of tissues, has good structural stability and cell compatibility, is beneficial to the growth, adhesion and proliferation of host cells, and thus induces the orderly remodeling of tissues.

[0094] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. A collagen membrane with the function of inducing orderly tissue remodeling, characterized in that, the collagen membrane is obtained by hot pressing a fiber membrane; the fiber membrane is formed by cross - laminating fibers with an average diameter of 0.5 - 15 μm; the fibers include collagen and poly(L - lactide - caprolactone), and the mass ratio of collagen to poly(L - lactide - caprolactone) is 1:(1.5 - 2.5).

2. The collagen membrane according to claim 1, characterized in that, the mass ratio of collagen to poly(L - lactide - caprolactone) is 1:(1.8 - 2.2).

3. The collagen membrane according to claim 1, characterized in that, the thickness of the fiber membrane is 50 - 300 μm.

4. The collagen membrane according to claim 1, characterized in that, the temperature of the hot pressing treatment is 40 - 48 °C, and the time is 15 - 40 min.

5. The collagen membrane according to claim 4, characterized in that, the pressure of the hot pressing treatment is 100 - 160 Pa.

6. A preparation method of the collagen membrane according to any one of claims 1 - 5, characterized in that, it includes the following steps: S1. Electrospinning a spinning solution to prepare a fiber membrane; S2. Performing hot pressing treatment on the fiber membrane in S1 to obtain the collagen membrane; wherein, the spinning solution in S1 includes collagen and poly(L - lactide - caprolactone).

7. The preparation method according to claim 6, characterized in that, the mass ratio of collagen to poly(L - lactide - caprolactone) is 1:(1.5 - 2.5); and / or, the mass concentration of collagen is 5 - 10 g / mL, and the mass concentration of poly(L - lactide - caprolactone) is 10 - 20 g / mL.

8. The preparation method according to claim 6, characterized in that, the spinning solution is composed of collagen, poly(L - lactide - caprolactone), hexafluoroisopropanol, acetic acid and water.

9. The preparation method according to claim 6, characterized in that, the voltage of the electrospinning is 25 - 40 kV.

10. An application of the collagen membrane according to any one of claims 1 - 5 in the preparation of a tissue regeneration membrane.

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