CN117462755A - Biological repair material and preparation method and application thereof - Google Patents

Abstract

The invention relates to the technical fields of biological medicine and biological materials, and discloses a biological repair material, a preparation method and application thereof. The bioremediation material includes a substrate and a bioadhesive layer; the substrate and the bioadhesive layer are combined through a cross-linked structure formed by irradiation cross-linking. The method comprises the following steps: spreading the biological adhesive solution on a substrate, and sequentially carrying out defoaming treatment, irradiation crosslinking treatment and freeze-drying treatment to obtain the biological repair material. The components of the substrate and the bioadhesive layer in the biological repair material provided by the invention both contain collagen, and the components are crosslinked by irradiation, so that the collagen molecules are crosslinked into the stereo reticular molecules from the original linear macromolecules by using water molecules as a medium, and the substrate and the bioadhesive layer are chemically combined, so that the mechanical strength of the substrate and the bioadhesive layer is increased, and the phenomena of unstable adhesion, connection falling and the like in the using and repairing processes are avoided.

Description

Biological repair materials and preparation methods and applications thereof

Technical field

The invention relates to the technical fields of biomedicine and biomaterials, and in particular to a biological repair material and its preparation method and application.

Background technique

Self-adhesive repair materials can eliminate the need for surgical sutures, greatly reducing surgical time and reducing surgical risks.

Self-adhesive repair materials are generally divided into two structures: one is the self-adhesive part with adhesive function, and the other is the film base material with shielding and repair functions. Existing repair materials have the following problems: (1) The self-adhesive glue and the membrane base material are mostly physically connected using the adhesive force of the self-adhesive part itself, and there is a risk of falling off during use; (2) The self-adhesive glue is Some are degradable polyester medical self-adhesive layers or α-cyanobutyl acrylate medical self-adhesive layers. This type of medical adhesive has strong adhesion, but lacks elasticity and toughness; (3) Existing film base materials They are polymer synthetic materials or animal-derived materials, such as polylactic acid, polyglycolic acid, or bovine pericardial tissue, bovine tendon, pig pericardium, etc. These membrane materials have poor degradation performance or do not have degradation performance; (4) Existing self-adhesive repair materials are mostly used for dura mater repair and cannot be used for various tissue repairs.

Contents of the invention

In order to solve one or more technical problems in the prior art, the present invention provides a biological repair material and its preparation method and application.

In the biological repair material of the present invention, the adhesive force between the base and the biological adhesive layer is strengthened through cross-linking. The biological adhesive layer has high bonding properties, good biocompatibility, good elasticity and toughness, and is It can maintain viscosity and strength in a wet environment; the substrate has good mechanical properties, biocompatibility and degradability. The biological repair material of the present invention can be used to repair various tissues such as dura mater, oral cavity, abdominal wall, epidermis, tendon, etc.

In order to achieve the above object, the first aspect of the present invention provides a biological repair material. The biological repair material includes a base and a biological adhesive layer; the base is an acellular tissue membrane or an electrospun collagen membrane; the biological adhesive layer The mixture layer is made of a bioadhesive including collagen;

Wherein, the substrate and the bioadhesive layer are combined through a cross-linked structure formed by irradiation cross-linking.

A second aspect of the present invention provides a method for preparing the biological repair material described in the first aspect. The method includes: spreading a biological adhesive solution on a substrate, and sequentially performing defoaming treatment, radiation cross-linking treatment, and The biological repair material is obtained after freeze-drying.

A third aspect of the present invention provides a biological repair material prepared by the preparation method described in the second aspect.

A fourth aspect of the present invention provides the application of the biological repair material described in the first or third aspect in tissue repair.

Through the above technical solutions, the beneficial technical effects achieved by the present invention are as follows:

(1) The components of the base and the bioadhesive layer in the biological repair material provided by the present invention both contain collagen. The two are cross-linked by irradiation, using water molecules as the medium, thereby converting the collagen molecules from The original linear macromolecules are cross-linked into three-dimensional network molecules to chemically bond the substrate and the bioadhesive layer, thereby increasing the mechanical strength of both and ensuring that there will be no weak bonding during use and repair. , connections falling off and other undesirable phenomena;

(2) The base and biological adhesive layer in the biological repair material provided by the present invention are made of completely absorbable materials, and these materials have good biocompatibility; the base is an acellular tissue membrane or an electrospun collagen membrane, It has gaps to facilitate the rapid growth of cells and facilitate tissue repair; the biological adhesive layer can assist in fixing the base, avoid secondary trauma caused by the fixation process, and can provide a sealing effect, making the biological repair material of the present invention particularly suitable for sealing. Leak sealing fluid, leaking wounds and incisions;

(3) The degradation cycle of the biological repair material of the present invention itself is controllable, and different products can be designed for use in different locations and indications.

Description of the drawings

Figure 1 is a schematic structural diagram of the biological repair material according to the present invention;

Figure 2 is a 4.5x electron microscope view of the biological repair material prepared in Example 1 of the present invention;

Figure 3 is a front view of the biological repair material product prepared in Example 1 of the present invention;

Figure 4 is a back view of the biological repair material product prepared in Example 1 of the present invention;

Figure 5 is the test chart of the tensile testing machine;

Figure 6 is a schematic diagram of a trapezoidal template.

Among them: 1-base; 2-cross-linked structure; 3-bioadhesive layer.

Detailed ways

The endpoints of ranges and any values disclosed herein are not limited to the precise range or value, but these ranges or values are to be understood to include values approaching such ranges or values. For numerical ranges, the endpoint values of each range, the endpoint values of each range and individual point values, and the individual point values can be combined with each other to obtain one or more new numerical ranges. These values The scope shall be deemed to be specifically disclosed herein.

A first aspect of the present invention provides a biological repair material. The biological repair material includes a base and a biological adhesive layer; the base is an acellular tissue membrane or an electrospinning collagen membrane; the biological adhesive layer is composed of Made of collagen bioadhesive;

Wherein, the substrate and the bioadhesive layer are combined through a cross-linked structure formed by irradiation cross-linking.

The structure of the biological repair material of the present invention is shown in Figure 1.

In some embodiments of the present invention, the acellular tissue membrane is selected from one of acellular porcine intestinal submucosa, acellular dermal matrix or acellular pericardium.

The preparation process of the decellularized tissue membrane includes steps such as pretreatment, virus inactivation, decellularization, cleaning, and molding. The methods used in each step are common methods in the prior art. The decellularization step uses an acid-base method for decellularization. cell. The specific method is: use acid solution or alkaline solution to decellularize the virus-inactivated porcine small intestinal submucosa matrix material in an ultrasonic cleaning machine.

The acid solution used can be one or more of hydrochloric acid, sulfuric acid, nitric acid, and formic acid. The concentration of the acid solution is 0.001-1 mol/L. The volume of the acid solution is the pretreated pig small intestine. 2-20 times the volume of the material, the time for decellularization with acid solution is 30-120 minutes; the alkali solution can be KOH solution and/or NaOH solution, the concentration of the alkali solution is 0.001-1mol/L, the alkali solution The volume of the solution should be 2-20 times the volume of the pretreated pig small intestine material, and the decellularization time with the alkaline solution should be 30-120 minutes.

The molding operation can be carried out by drying or freeze-drying.

In some embodiments of the present invention, the electrospun collagen membrane is prepared by electrospinning a mixture of collagen fibers and L-arginine.

The preparation process includes preparing a collagen fiber solution, preparing an L-arginine solution, mixing the two solutions, and electrospinning with an electrospinning machine.

In some embodiments of the invention, the bioadhesive layer is made of a bioadhesive including a supercharged protein and a surfactant; the surfactant is a cationic surfactant or anionic azobenzene Surfactant-like; the cationic surfactant has a catechol structural unit.

In some embodiments of the present invention, the bioadhesive is composed of a super positively charged protein and an anionic azobenzene surfactant; or, the bioadhesive is composed of a super negatively charged protein and a cationic surfactant. agent composition.

In some embodiments of the invention, the thickness of the substrate is 0.05-0.15 mm, and the thickness of the bioadhesive layer is 2-5 mm.

In some embodiments of the invention, the thickness of the substrate is 0.16-0.25 mm, and the thickness of the bioadhesive layer is 6-10 mm.

In some embodiments of the invention, the thickness of the substrate is 0.26-0.35 mm, and the thickness of the bioadhesive layer is 11-15 mm.

The above three thickness combinations of base and bioadhesive layer represent three different types of bioprosthetic materials, namely low type, medium type and high type.

The biological repair material of the present invention can be used to repair various tissues such as dura mater, oral cavity, hernia defect, skin defect, tendon, etc. According to the needs of different tissues, different types of repair materials can be used to repair different tissues, such as Low-type repair materials can be used to repair dura mater or oral cavity, medium-type repair materials can be used to repair hernia defects or skin defects, and high-type repair materials can be used to repair tendons and other tissues.

A second aspect of the present invention provides a method for preparing the biological repair material described in the first aspect. The method includes: spreading a biological adhesive solution on a substrate, and sequentially performing defoaming treatment, radiation cross-linking treatment, and The biological repair material is obtained after freeze-drying.

The above preparation method can be carried out in a mold, such as a mold box with a certain height, length and width. The material can be polymer materials such as organic glass, polytetrafluoroethylene, or metal materials such as stainless steel.

In some embodiments of the present invention, the method of defoaming treatment is vibration defoaming or vacuum defoaming. Ultrasonic vibration can be used for vibration defoaming, and a vacuum box can be used for vacuum defoaming. The vacuum degree during vacuum defoaming is -40 to -80KPa. In the present invention, if the vacuum is too small, the defoaming effect cannot be achieved; if the vacuum is too small, the upper bioadhesive will overflow from the mold.

In some embodiments of the present invention, 60Co gamma rays are used for radiation cross-linking treatment.

In some embodiments of the invention, the irradiation dose is 5-15 kGy.

In the present invention, the following scheme can be adopted for freeze-drying: the freeze-drying includes a pre-freezing stage, a first sublimation stage, a second sublimation stage and a cooling stage. The process conditions of each stage are as follows:

Pre-freezing stage: target temperature is -20 to -15°C, rate is 3-4.0°C/min, and constant temperature duration is 160-240min;

The first sublimation stage: vacuuming, the vacuum degree is lower than -0.05MPa, and the aeration is 50-120Pa, including three heating steps, namely:

-10 to -8℃, the rate is 0.2-0.3℃/min, the constant temperature duration is 150-180min;

1～2℃, the rate is 0.1-0.2℃/min, the constant temperature duration is 150-180min;

4～10℃, the rate is 0.3-0.4℃/min, the constant temperature duration is 180-240min;

The second sublimation stage: vacuuming, the vacuum degree is lower than -0.05MPa, and the aeration is 50-120Pa, including four heating steps, namely:

14-20℃, the rate is 1.0-1.2℃/min, the constant temperature duration is 120-140min;

22-32℃, the rate is 1.0-1.2℃/min, the constant temperature duration is 120-140min;

34-38℃, the rate is 1.6-1.8℃/min, the constant temperature duration is 70-80min;

42-45℃, the rate is 1.6-1.8℃/min, constant temperature duration: the end point is judged every 1 hour until the end point is judged qualified; the end point is ≤0.5Pa/10min;

Cooling stage: to room temperature at a rate of 4-6°C/min.

A third aspect of the present invention provides a biological repair material prepared by the preparation method described in the second aspect.

A fourth aspect of the present invention provides the application of the biological repair material described in the first or third aspect in tissue repair.

In some embodiments of the invention, the tissue is dura mater, oral cavity, abdominal wall, abdominal hernia, skin or tendon.

According to a particularly preferred embodiment of the present invention, a method for preparing self-adhesive biological repair materials includes the preparation of biological adhesives, the preparation of acellular pig small intestinal submucosa matrix, and the preparation of self-adhesive biological repair materials, The method includes the following steps:

(1) Transform the super positively charged protein K series or super negatively charged protein E series vector plasmids into E. coli expression strains (BL21/BL21DE3/BLRD E3) for overexpression. After induction for 12 hours, collect the cells, resuspend them in lysis buffer, add protease inhibitors, DNase, and lysozyme, crush the cells with a high-pressure crusher, centrifuge at 10,000 rpm or above, collect the supernatant, and purify by HPLC to finally obtain supernormal Charged protein K or super-negatively charged protein E;

(2) Add the surfactant solution dropwise to the supercharged protein solution and mix evenly to obtain a binder solution; wherein, the superpositively charged protein K needs to be mixed with an anionic azobenzene surfactant, and the supernegatively charged protein K needs to be mixed with an anionic azobenzene surfactant. Protein E needs to be mixed with cationic surfactants;

(3) Take the pig small intestine submucosa material, remove surface fat and lymphoid tissue, and wash it with an ultrasonic cleaning machine to obtain pretreated submucosa material;

(4) Soak the pretreated porcine small intestinal submucosa raw material obtained in step (3) with a "peroxyacetic acid-ethanol" solution in an ultrasonic cleaning machine, and then wash it with purified water to obtain virus-inactivated mucosa. underlying material;

(5) Decellularize the virus-inactivated submucosal material obtained in step (4) with an acid solution or an alkali solution in an ultrasonic cleaning machine; repeat this step 1-5 times after replacing the solution (for example, 1, 2, 3, 4 or 5 times) to obtain decellularized materials;

(6) Fix the decellularized porcine small intestinal submucosa matrix material obtained in step (5) onto a mold, and dry or freeze-dry to obtain the decellularized porcine small intestinal submucosa matrix;

(7) Select the corresponding mold box, place the acellular porcine small intestinal submucosa matrix obtained in step (6) on the bottom of the mold, measure a certain amount of the adhesive solution obtained in step (2), inject it into the mold and shake evenly. Keep the liquid level smooth;

(8) Place the injected mold into ultrasonic equipment or a vacuum box, eliminate bubbles in the liquid in the mold, and measure the thickness of the product;

(9) The defoamed material is irradiated and cross-linked, and the irradiation dose is selected from 5-15KGy;

(10) Put the radiation-crosslinked material into a freeze-drying machine and freeze-dry it to obtain an absorbable biological repair material with a self-adhesive structure.

The present invention will be described in detail below through examples.

If specific conditions are not specified in the following examples and comparative examples, the conditions should be carried out in accordance with conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not indicated, they are all conventional products that can be purchased commercially.

Example 1

This example is used to illustrate the preparation of biological repair materials.

(1) Transform the super positively charged protein K series vector plasmid into an E. coli expression strain, collect the cells after 12 hours of expression induction, resuspend, disrupt, centrifuge, collect the supernatant, and purify to obtain super positively charged protein K;

(2) Add the anionic azobenzene surfactant solution dropwise to the supercharged protein K solution and mix evenly to obtain a binder solution;

(3) Take the pig small intestine submucosa material, remove surface fat and lymphoid tissue, and wash it with an ultrasonic cleaning machine to obtain pretreated submucosa material;

(4) Soak the pretreated porcine small intestinal submucosa raw material obtained in step (3) with a "peroxyacetic acid-ethanol" solution in an ultrasonic cleaning machine, and then wash it with purified water to obtain virus-inactivated mucosa. The lower layer material, in which the "peracetic acid-ethanol" solution composition is: peracetic acid:ethanol:water=1:24:75, the frequency of the ultrasonic cleaning machine is 40kHz, and the processing time is 60min;

(5) Use an acid solution in an ultrasonic cleaning machine to decellularize the virus-inactivated submucosal material obtained in step (4); the acid solution is hydrochloric acid with a concentration of 0.5 mol/L, and the volume of hydrochloric acid is the step ( 4) Obtain 10 times the material, the frequency of the ultrasonic cleaning machine is 25kHz, and the time for decellularization with acid solution is 60 minutes;

(6) Fix the decellularized porcine small intestinal submucosa matrix material obtained in step (5) to the mold and freeze-dry to obtain an acellular porcine small intestinal submucosa matrix with a thickness of 0.15 mm;

(7) Select a mold box with a size of 15 cm Inject the mixture solution into the mold with a height of 4mm, shake evenly, and try to keep the liquid level as flat as possible;

(8) Place the injected mold into a vacuum box to eliminate bubbles in the liquid in the mold;

(9) The defoamed material is irradiated and cross-linked with 60Coγ rays, and the irradiation dose is selected as 5kGy;

(10) After radiation cross-linking treatment, the material is placed in a freeze-drying machine for freeze-drying to obtain an absorbable biological repair material with a self-adhesive structure. This material can be used to repair the oral cavity and dura mater.

Figure 2 is a 4.5x electron microscope view of the biological repair material;

Figure 3 is a front view of the biological repair material product;

Figure 4 is a back view of the biological repair material product;

Example 2

This example is used to illustrate the preparation of biological repair materials.

(1) Transform the super negatively charged protein E series vector plasmid into an E. coli expression strain, collect the cells after 12 hours of expression induction, resuspend, disrupt, centrifuge, collect the supernatant, and purify to obtain the super positively charged protein E;

(2) Add dropwise the cationic surfactant solution having a catechol structural unit to the supercharged protein E solution, and mix evenly to obtain a binder solution;

(3) Take the pig small intestine submucosa material, remove surface fat and lymphoid tissue, and wash it with an ultrasonic cleaning machine to obtain pretreated submucosa material;

(4) Soak the pretreated porcine small intestinal submucosa raw material obtained in step (3) with a "peroxyacetic acid-ethanol" solution in an ultrasonic cleaning machine, and then wash it with purified water to obtain virus-inactivated mucosa. The lower layer material, in which the "peracetic acid-ethanol" solution composition is: peracetic acid:ethanol:water=1:24:75, the frequency of the ultrasonic cleaning machine is 40kHz, and the processing time is 60min;

(5) Use an alkali solution to decellularize the virus-inactivated submucosal material obtained in step (4) in an ultrasonic cleaning machine; the alkali solution is a NaOH solution with a concentration of 0.5 mol/L, and the volume of NaOH is the step (4) Obtain 5 times the material, the frequency of the ultrasonic cleaning machine is 25kHz, and the time for decellularization with alkaline solution is 60 minutes;

(6) Fix the decellularized porcine small intestinal submucosa matrix material obtained in step (5) to the mold and freeze-dry to obtain an acellular porcine small intestinal submucosa matrix with a thickness of 0.25 mm;

(7) Select a mold box with a size of 15 cm Inject the mixture solution into the mold at a height of 12mm, shake evenly, and try to keep the liquid level as flat as possible;

(8) Place the injected mold into a vacuum box to eliminate bubbles in the liquid in the mold;

(9) The defoamed material is irradiated and cross-linked with 60Coγ rays, and the irradiation dose is 10kGy;

(10) Put the cross-linked material into a freeze-drying machine for freeze-drying to obtain an absorbable biological repair material with a self-adhesive structure. This material can be used for tendon repair.

Example 3

This example is used to illustrate the preparation of biological repair materials.

(1) Transform the super positively charged protein K series vector plasmid into an E. coli expression strain, collect the cells after 12 hours of expression induction, resuspend, disrupt, centrifuge, collect the supernatant, and purify to obtain super positively charged protein K;

(2) Add the anionic azobenzene surfactant solution dropwise to the supercharged protein K solution and mix evenly to obtain a binder solution;

(3) Under the action of magnetic stirring, dissolve collagen in an acetic acid solution (acetic acid concentration is 25wt%) to form a 1wt% collagen fiber solution, which is solution 1; dissolve L-arginine hydrochloride In an acetic acid solution (acetic acid concentration is 20wt%), configure a 7wt% L-arginine solution to become solution 2;

(4) Mix solution 1 and solution 2 at a mass ratio of 9:1 and perform electrospinning. The electrospinning parameters are set as follows: electrospinning distance 15cm, electrospinning voltage 15kV, solution flow rate 2mL/h, and receiving device The rotation speed is 500rpm and the syringe traverse speed is 10cm/min; the collagen fiber membrane is collected on the flat aluminum foil receiving device; the obtained nanofiber membrane is vacuum dried for 24 hours to obtain an electrospun collagen membrane with a thickness of 0.2mm;

(5) Select a mold box with a size of 15cm×10cm×2.5cm, cut the electrospun collagen film obtained in step (4) into 15cm×10cm, lay it on the bottom of the mold, and then put the adhesive obtained in step (2) Inject the solution into the mold with a height of 4mm, shake evenly, and try to keep the liquid level as flat as possible;

(6) Place the injected mold into a vacuum box to eliminate bubbles in the liquid in the mold;

(7) The defoamed material is irradiated and cross-linked using 60Coγ rays, and the irradiation dose is selected to be 5kGy;

(8) After radiation cross-linking treatment, the material is placed in a freeze-drying machine for freeze-drying to obtain an absorbable biological repair material with a self-adhesive structure. This material can be used to repair the oral cavity and dura mater.

Comparative example 1

The self-adhesive dural patch prepared in Example 2 of CN108272529A was used as Comparative Example 1.

Test Example 1 Breaking Strength and Tensile Strength Test

According to the standard method of GB/T 3923.1-2013, the materials of Examples 1, 2 and Comparative Example 1 were trimmed into 150mm×50mm rectangular specimens, and the specimens were placed on the testing machine for tensile strength testing. The experimental conditions were: The gauge length is 100mm, the stretching speed is 50mm/min, and the pretension is 2N. As shown in Figure 5.

The results are shown in Table 1.

Table 1

project Breaking strength/N Tensile strength/N/cm Elongation at break/% Example 1 224.3 44.86 34.45 Example 2 563.2 82.3 58.6 Comparative example 1 58.6 11.72 18.63

It can be seen from the results in Table 1 that the biological repair materials prepared in Examples 1 and 2 have significantly improved tensile strength and elongation at break compared with existing materials, and can meet the clinical needs of repair materials.

Test Example 2 Tear Strength Test

According to the method specified in GB/T 3917.3-2009, the materials of Examples 1, 2 and Comparative Example 1 were cut into rectangular specimens of 150 mm × 75 mm, and cut according to the trapezoidal template diagram (as shown in Figure 6), and the specimens were The sample was placed on the testing machine for tear strength testing. The experimental conditions were: the gauge length was 25mm and the tensile speed was 100mm/min.

The results are shown in Table 2.

Table 2

project Tear strength/N Example 1 107.3 Example 2 246.1 Comparative example 1 36.2

It can be seen from the test results in Table 2 that the tear strength of the materials prepared in Examples 1 and 2 has been greatly improved compared with existing materials.

Test Example 3 Peel Strength Test

According to the standard method of GB/T 2791-1995, prepare a "T"-shaped opening sample. The total length of the sample is 200mm, the length of the bonded part is 150mm, and the width of the sample is 25mm. Place the sample on the testing machine for tearing. Crack strength test, experimental conditions are: tensile speed is 100mm/min.

The results are shown in Table 3.

table 3

project Peeling force/N Peel strength/N/cm Example 1 15.6 6.24 Example 2 16.9 7.02 Comparative example 1 8.5 3.40

It can be seen from the test results in Table 3 that the materials prepared in Examples 1 and 2 significantly increase the connection strength between the bioadhesive layer and the base film material through irradiation cross-linking, and have a higher peeling force than existing materials. and peel strength have been significantly improved.

It can be seen from the above results that the connection between the self-adhesive layer and the film base material in Comparative Example 1 only relies on the physical viscosity of the self-adhesive itself, and there is a risk of cracking and falling off during use. The bioadhesive of the present invention The layer and base material are cross-linked by radiation to form a three-dimensional network structure, which greatly enhances the connection strength between the two. Conclusions can be drawn from the comparative test of peel force and peel strength.

The pressure-sensitive adhesive of the self-adhesive layer in Comparative Example 1 is a non-absorbable material. The bioadhesive used in the present invention can be degraded in the body and has good biocompatibility.

The membrane base material in Comparative Example 1 is a collagen sponge. The large thickness of 5mm collagen sponge is not conducive to surgical operation, and the mechanical properties of the sponge are poor. The membrane base material of the present invention is a multi-layer acellular matrix or an electrospinning polymer absorbable material. , has good mechanical properties, and the breaking strength, tensile strength, tear strength and other properties are better than those of Comparative Example 1. It can be concluded from the relevant comparative tests.

The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the scope of the technical concept of the present invention, many simple modifications can be made to the technical solution of the present invention, including the combination of various technical features in any other suitable manner. These simple modifications and combinations should also be regarded as the disclosed content of the present invention. All belong to the protection scope of the present invention.

Claims (10)

1. A bioremediation material, wherein the bioremediation material comprises a substrate and a bioadhesive layer; the substrate is a decellularized tissue membrane or an electrostatic spinning collagen membrane; the bioadhesive layer is made of a bioadhesive comprising collagen;

wherein the substrate and the bioadhesive layer are combined through a cross-linked structure formed by irradiation cross-linking.

2. The bioprosthetic material of claim 1, wherein the decellularized tissue membrane is selected from one of a decellularized porcine small intestine submucosa, a decellularized dermal matrix, or a decellularized pericardium.

3. The bioremediation material of claim 1 or 2, wherein the electrospun collagen film is prepared by electrospinning a mixture of collagen fibers and L-arginine.

4. The bioremediation material of any one of claims 1-3, wherein the bioadhesive layer is made of a bioadhesive comprising a super charged protein and a surfactant; the surfactant is a cationic surfactant or an anionic azobenzene surfactant; the cationic surfactant has catechol building blocks.

5. The bioremediation material of claim 4, wherein the bioadhesive consists of a super-positively charged protein and an anionic azobenzene surfactant; alternatively, the bioadhesive consists of a super-negatively charged protein and a cationic surfactant.

6. The bioremediation material of any one of claims 1-5, wherein the thickness of the substrate is 0.05mm-0.15mm and the thickness of the bioadhesive layer is 2-5mm;

preferably, the thickness of the substrate is 0.16mm to 0.25mm, and the thickness of the bioadhesive layer is 6mm to 10mm;

preferably, the thickness of the substrate is 0.26-0.35mm, and the thickness of the bioadhesive layer is 11-15mm.

7. A method of preparing a bioremediation material according to any one of claims 1-6, wherein said method comprises: spreading the biological adhesive solution on a substrate, and sequentially carrying out defoaming treatment, irradiation crosslinking treatment and freeze-drying treatment to obtain the biological repair material.

8. The preparation method according to claim 7, wherein the defoaming treatment is performed by vibration defoaming or vacuum defoaming;

preferably, the vacuum degree during vacuum defoaming is-40 to-80 KPa;

preferably, the irradiation crosslinking treatment is carried out by adopting 60Co gamma rays;

preferably, the irradiation dose is 5-15kGy.

9. A bioremediation material made according to the method of making of claim 7 or 8.

10. Use of the bioremediation material of any one of claims 1-6 or 9 in tissue repair;

preferably, the tissue is dura mater, oral cavity, abdominal wall, external abdominal hernia, skin or tendon.