Anti-adhesion growth-promoting degradable mesh and preparation method and application thereof

Abstract

The application patent belongs to the technical field of biomedical materials, and specifically discloses a degradable patch capable of preventing adhesion and promoting growth, which comprises an anti-adhesion layer, a polydopamine layer and a growth promotion layer connected in sequence, wherein the anti-adhesion layer and the growth promotion layer both comprise a high-molecular degradable polymer, and the high-molecular degradable polymer comprises one or more of polyhydroxyalkanoate, polylactic acid and polycaprolactone. The patch has the advantages of simple and easy preparation, double anti-adhesion effects of physical structure and chemical composition, good biocompatibility, tissue regeneration promotion function, controllable degradation speed of the patch, and the problems of obvious foreign body sensation after operation, organ adhesion, and early shedding of the patch are solved.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, and more specifically, relates to a biodegradable patch that prevents adhesion and promotes growth, as well as its preparation method and application. Background Technology

[0002] Abdominal wall defects, a common soft tissue defect in clinical practice, are primarily treated with filling and repair materials. However, this approach is costly, and ideal repair materials are scarce, severely impacting patient prognosis and quality of life. In my country, at least 3.5 million new cases of abdominal wall defects are diagnosed annually. Currently, PP (polypropylene) patches are widely used for intra-abdominal repair. However, these patches are non-degradable, posing risks such as organ adhesions, intestinal obstruction, and bacterial infection. Furthermore, as foreign bodies, the implanted patch material can induce chronic inflammation, leading to fibroblast aggregation and adhesion formation. Therefore, biocompatible, biodegradable patches represent the future direction for soft tissue repair.

[0003] Furthermore, the topological structure of a material surface can influence cell spreading, morphology, proliferation, and migration. Fiber scaffolds fabricated using electrospinning technology possess a fibrous structure similar to the natural extracellular matrix (ECM), and are therefore widely used in cell proliferation culture, drug delivery, and biosensors. With the deepening of tissue engineering research, electrospinning technology continues to develop, giving rise to different spinning processes and methods, resulting in fiber scaffolds with distinctly different properties, capable of meeting the needs of various tissues. Summary of the Invention

[0004] The present invention aims to overcome the defects of the prior art and provide a biodegradable patch that prevents adhesion and promotes growth. The biodegradable patch that prevents adhesion and promotes growth has good biocompatibility, can be degraded in vivo, and effectively meets clinical needs.

[0005] To achieve the above objectives, the technical solution is as follows:

[0006] A biodegradable patch for preventing adhesion and promoting growth includes an anti-adhesion layer, a polydopamine layer, and a growth-promoting layer connected in sequence. The anti-adhesion layer is made of a biodegradable polymer by electrospinning technology, the polydopamine layer is made by dopamine surface self-assembly technology, and the growth-promoting layer is made of a biodegradable polymer mixed with collagen by electrospinning technology.

[0007] The aforementioned biodegradable polymer comprises one or more of polyhydroxyalkanoates, polylactic acid (L-lactic acid), and polycaprolactone. All three components are biodegradable in vivo, exhibiting good biocompatibility and effectively reducing inflammatory responses and postoperative complications after patch implantation, demonstrating significant superiority over materials such as polypropylene, which are difficult to degrade in vivo.

[0008] The dopamine surface self-assembly technology involves the in-situ polymerization of dopamine on the surface of the anti-adhesion layer to form a polydopamine nano-coating. This coating is stable, has good hydrophilicity and biocompatibility, and isolates the anti-adhesion layer from the growth-promoting layer, preventing the growth-promoting layer from directly contacting abdominal organs and reducing the incidence of complications such as intestinal adhesions.

[0009] The fiber pore size of the anti-adhesion layer is 5-30 μm, and the fiber pore size of the growth-promoting layer is 150-250 μm.

[0010] Preferably, the thickness of the anti-adhesion layer and the growth-promoting layer can be adjusted according to different needs.

[0011] The method for preparing the biodegradable patch includes the following steps:

[0012] Step S1: Select a suitable organic solvent to dissolve the biodegradable polymer, stir with a magnetic stirrer for 2-8 hours to form a uniform electrospinning working solution at a temperature of 30-45℃, and the concentration of the biodegradable polymer in the working solution is 8-18% g / mL.

[0013] Step S2: Transfer the working solution prepared in step S1 into a 10mL syringe and sonicate it to remove air bubbles. Fix the syringe with a needle nozzle. The spinning environment temperature is 20-60℃, humidity is 20-50%, the distance between the needle and receiver is 10-20cm, the voltage is 8-30KV, the syringe advance speed is 0.3-12.0mL / h, and the take-up drum speed is 30-150r / min. By adjusting the electrode receiving method and receiving time, the pore size of the spun fibers can be controlled, thereby changing their surface topology and completing the preparation of the anti-adhesion layer.

[0014] Step S3: After drying the anti-adhesion layer prepared in step S2, dopamine self-assembly is performed on its surface to form a dense polydopamine nano-coating, thereby completing the chemical surface modification of the patch and achieving the dual anti-adhesion effect of the patch's physical structure and chemical composition.

[0015] Step S4: Reattach the polydopamine-modified anti-adhesion layer prepared in Step S3 to the receiver. Add collagen fibers to the working solution and adjust the electrospinning parameters in S2. Add a growth-promoting layer to one side of the polydopamine layer of the anti-adhesion layer. After vacuum drying for 8-12 hours, a biodegradable patch with anti-adhesion and growth-promoting functions can be obtained. Prepare it into the required shape as needed, sterilize it, and it can be used or stored in a vacuum.

[0016] Preferably, the organic solvent in step S1 is one or a mixture of more than one of dichloromethane, trichloromethane, and N,N-dimethylformamide.

[0017] The self-assembly process of the anti-adhesion layer surface in step S3 is as follows: The anti-adhesion layer is placed in deionized water for later use. A 1-3 g / L dopamine solution is prepared using a Tris-HCl buffer solution with pH = 7.0-8.5 as the solvent. The anti-adhesion layer is immersed in the newly prepared dopamine buffer solution and reacted at room temperature for 4-12 hours. After this reaction, the membrane is removed and thoroughly shaken and washed with deionized water and ethanol to obtain a modified anti-adhesion layer with a polydopamine composite layer attached to its surface. The membrane is then thoroughly shaken and washed with deionized water and ethanol and dried for later use.

[0018] Preferably, in the working solution described in step S4, the amount of collagen fibers added is 1-8% g / mL. By introducing collagen, the biocompatibility of the patch is further improved, cell adhesion and proliferation are promoted, thereby achieving the purpose of promoting tissue repair and regeneration.

[0019] Preferably, the three components of the biodegradable polymer, polyhydroxyalkanoate, polylactic acid, and polycaprolactone, are all of medical grade purity, with a purity greater than 99.5%, and their molecular weight is between 80 and 250k.

[0020] Preferably, the degradation rate of the patch can be controlled by adjusting the addition ratio and molecular weight of the aforementioned three components, with a degradation rate of 6-12 months.

[0021] This invention also discloses the application of the aforementioned anti-adhesion and growth-promoting biodegradable patch in the fields of cell scaffolds and soft tissue repair medicine.

[0022] The beneficial effects of this invention are as follows:

[0023] (1) The biodegradable patch for preventing adhesion and promoting growth described in this invention selects biodegradable polymers as the base material and controls the addition ratio and molecular weight of different polymers to control the degradation rate of the patch, ensuring that the patch has good mechanical compatibility with the surrounding tissue during the degradation process and avoiding premature decomposition and shedding.

[0024] (2) By relying on electrospinning technology and dopamine surface self-assembly technology, a specific topological structure is constructed on the surface of the patch and chemically modified, thus realizing the design of the patch. One side can promote muscle tissue regeneration, and the other side can effectively reduce organ adhesion, thereby achieving precise soft tissue repair, making up for the shortcomings of existing patches, meeting different clinical needs, and having broad development prospects. Attached Figure Description

[0025] Figure 1 The results are from a scanning electron microscope (SEM) of the anti-adhesion layer of the patch.

[0026] Figure 2 The results are from scanning electron microscopy of the growth layer of the patch.

[0027] Figure 3 This is a schematic diagram of a patch being used in abdominal wall repair.

[0028] Figure 4 This is a photograph of the inner side of the abdominal wall of a rat using a patch for abdominal wall repair.

[0029] Labeling explanations: 301-Skin, 302-Fat, 303-Muscle, 304-Suture, 305-Growth-promoting layer, 306-Polydopamine layer, 307-Anti-adhesion layer, 308-Intestinal segment. 4c-Control group, 4d-Experimental group. Detailed Implementation

[0030] The accompanying drawings are for illustrative purposes only and should not be construed as limiting the invention. To better illustrate the following embodiments, some parts in the drawings may be omitted, enlarged, or reduced, and do not represent the actual product dimensions; it is understandable to those skilled in the art that some well-known structures and their descriptions may be omitted in the drawings.

[0031] Example 1

[0032] A method for preparing a biodegradable patch with anti-adhesion and growth-promoting properties includes the following steps:

[0033] S1. Preparation of electrospinning solution of polyhydroxy fatty acid ester: Weigh 0.8g of medical grade polyhydroxy fatty acid ester powder with a purity greater than 99.5%, dissolve it in 10mL of chloroform solution, stir with a magnetic stirrer for 8 hours at 35℃, and stir evenly to prepare a homogeneous solution for later use.

[0034] S2. Adjusting the surface topology of the patch: Add the polyhydroxyalkanoate electrospinning solution obtained in step S1 to a 10mL syringe. Fix the syringe with a needle nozzle. Under the conditions of 30℃ and 45% humidity, set the distance between the needle and the receiver to 15cm, the voltage to 15kV, the syringe advance speed to 3mL / hour, the rotation speed of the take-up drum to 50r / min, and the receiving time to 8min for each rotation speed to collect the electrospun fibers to form an anti-adhesion layer.

[0035] S3. After drying the anti-adhesion layer prepared in step S2, dopamine self-assembly is performed on its surface to form a dense polydopamine nano-coating, thus completing the chemical surface modification of the patch and achieving a dual anti-adhesion effect of physical structure and chemical composition. The specific process is as follows: A 1-3 g / L dopamine solution is prepared using a Tris-HCl buffer solution with pH=7.5 as the solvent. The anti-adhesion layer is immersed in the newly prepared dopamine buffer solution and reacted at room temperature for 6 hours. The membrane is then removed and thoroughly shaken and washed with deionized water and ethanol to obtain a modified anti-adhesion layer with a polydopamine composite layer attached to its surface. The membrane is then thoroughly shaken and washed with deionized water and ethanol and dried for later use.

[0036] S4. The polydopamine-modified anti-adhesion layer is reattached to the receiver. Collagen fibers are added to the polyhydroxyalkanoate electrospinning solution at a concentration of 3% g / mL. Electrospinning parameters are adjusted to design a loose, porous structure for the growth-promoting layer, aiming to further improve the patch's biocompatibility, promote cell adhesion and proliferation, and ultimately promote tissue repair and regeneration. Specific spinning parameters are as follows: The polyhydroxyalkanoate electrospinning solution obtained in step S4 is added to a 10mL syringe. The syringe is fixed with a needle nozzle. Under conditions of 30℃ and 45% humidity, the distance between the needle and receiver is set to 15cm, the voltage to 15kV, the syringe advance speed to 3mL / hour, and the take-up drum rotation speed to 110r / min. The receiving time for each rotation speed is set to 8min. The electrospun fibers are collected to form the growth-promoting layer. After vacuum drying for 12h, the polyhydroxyalkanoate patch is obtained. It is then prepared into the required shape and sterilized before use.

[0037] Scanning electron microscopy reveals that the anti-adhesion layer of the patch has dense fibers with small pores, such as... Figure 1 As shown; the fibers in the growth-promoting layer are relatively loose, with larger pore sizes, such as... Figure 2 As shown.

[0038] A schematic diagram of the polyhydroxyalkanoate patch used for peritoneal repair is shown below. Figure 3 As shown, the labels mean: 301-skin, 302-fat, 303-muscle, 304-suture, 305-growth-promoting layer, 306-polydopamine layer, 307-anti-adhesion layer, 308-intestinal segment. To test the anti-adhesion and growth-promoting effects of the patch, the polyhydroxyalkanoate patch was used in a control experiment of peritoneal repair surgery in SD rats. The experimental group underwent peritoneal repair surgery using the polyhydroxyalkanoate patch. Medial peritoneal photographs taken 4 weeks post-surgery are shown below. Figure 4 As shown in Figure d, the mesh structure in the image represents one side of the anti-adhesion layer of the patch, and the image shows no peritoneal bowel adhesions. The control group underwent peritoneal repair surgery without a patch; the medial peritoneum photograph 4 weeks post-surgery is shown below. Figure 4 As shown in Figure c, obvious adhesions are visible in the image.

[0039] Example 2

[0040] A method for preparing a biodegradable patch with anti-adhesion and growth-promoting properties includes the following steps:

[0041] S1. Preparation of polyhydroxyalkanoate / L-polylactic acid electrospinning solution: Weigh 0.6g / 0.4g of medical-grade P34HB powder of polyhydroxyalkanoate / L-polylactic acid with a purity greater than 99.5%, respectively, and dissolve them in 10mL of a composite solution of dichloromethane and dimethylformamide with a volume ratio of 5:5. Stir with a magnetic stirrer for 6 hours at a temperature of 35℃, and stir evenly to prepare a homogeneous solution for later use.

[0042] S2. Adjusting the surface topology of the patch: Add the electrospinning solution obtained in step S1 to a 10mL syringe. Fix the syringe with a needle nozzle. Under the conditions of 30℃ and 45% humidity, set the distance between the needle and the receiver to 12cm, the voltage to 13kV, the syringe advance speed to 3.5mL / hour, the rotation speed of the take-up drum to 60r / min, and the receiving time to 10min for each rotation speed to collect the electrospinned fibers to form an anti-adhesion layer.

[0043] S3. After drying the anti-adhesion layer prepared in step S2, dopamine self-assembly is performed on its surface to form a dense polydopamine nano-coating, thus completing the chemical surface modification of the patch and achieving a dual anti-adhesion effect of physical structure and chemical composition. The specific process is as follows: A 1.8 g / L dopamine solution is prepared using a Tris-HCl buffer solution with pH=8.0 as the solvent. The anti-adhesion layer is immersed in the newly prepared dopamine buffer solution and reacted at room temperature for 8 hours. After that, the membrane is taken out and thoroughly shaken and washed with deionized water and ethanol to obtain a modified anti-adhesion layer with a polydopamine composite layer attached to its surface. The membrane is thoroughly shaken and washed with deionized water and ethanol and then dried for later use.

[0044] S4. The polydopamine-modified anti-adhesion layer is reattached to the receiver. Collagen fibers are added to the uniform electrospinning solution obtained in step S1 at a rate of 5% g / mL. Electrospinning parameters are adjusted, and a loose, porous structure for the growth-promoting layer is designed to further enhance the patch's biocompatibility, promote cell adhesion and proliferation, and ultimately promote tissue repair and regeneration. Specific spinning parameters are as follows: The electrospinning solution obtained in step S4 is added to a 10mL syringe, which is fixed with a needle nozzle. Under conditions of 30℃ and 45% humidity, the distance between the needle and receiver is set to 12cm, the voltage to 13kV, the syringe advance speed to 3.5mL / hour, and the take-up drum rotation speed to 120r / min. Each rotation speed is used for 10min of receiving time. The electrospun fibers are collected to form the growth-promoting layer. After vacuum drying for 12 hours, a biodegradable patch with anti-adhesion and growth-promoting properties is obtained. It can be prepared into the required shape and sterilized before use.

[0045] Example 3

[0046] A method for preparing a biodegradable patch with anti-adhesion and growth-promoting properties includes the following steps:

[0047] S1. Preparation of electrospinning solution of polyhydroxy fatty acid ester / polylactic acid / polycaprolactone: Weigh 0.6g / 0.2g / 0.2g of polyhydroxy fatty acid ester / polylactic acid / polycaprolactone powder with a purity greater than 99.5% respectively, dissolve them in 10mL of a composite solution of chloroform and dimethylformamide with a volume ratio of 7:3, stir with a magnetic stirrer for 8 hours at 28℃, and stir evenly to prepare a homogeneous solution for later use.

[0048] S2. Adjusting the surface topology of the patch: Add the electrospinning solution obtained in step S1 to a 10mL syringe. Fix the syringe with a needle nozzle. Under the conditions of room temperature 28℃ and humidity 20%, set the distance between the needle and the receiver to 15cm, the voltage to 15kV, the syringe advance speed to 3.5mL / hour, the rotation speed of the take-up drum to 50r / min, and the receiving time to 10min for each rotation speed to collect the electrospinned fibers to form an anti-adhesion layer.

[0049] S3. After drying the anti-adhesion layer prepared in step S2, dopamine self-assembly is performed on its surface to form a dense polydopamine nano-coating, thus completing the chemical surface modification of the patch and achieving a dual anti-adhesion effect of physical structure and chemical composition. The specific process is as follows: A 2.2 g / L dopamine solution is prepared using a Tris-HCl buffer solution with pH=8.5 as the solvent. The anti-adhesion layer is immersed in the newly prepared dopamine buffer solution and reacted at room temperature for 12 hours. After that, the membrane is taken out and thoroughly shaken and washed with deionized water and ethanol to obtain a modified anti-adhesion layer with a polydopamine composite layer attached to its surface. The membrane is thoroughly shaken and washed with deionized water and ethanol and then dried for later use.

[0050] S4. The polydopamine-modified anti-adhesion layer is reattached to the receiver. Collagen fibers are added to the uniform electrospinning solution obtained in step S1 at a concentration of 8% g / mL. Electrospinning parameters are adjusted, and a loose, porous structure for the growth-promoting layer is designed to further enhance the patch's biocompatibility, promote cell adhesion and proliferation, and ultimately promote tissue repair and regeneration. Specific spinning parameters are as follows: The electrospinning solution obtained in step S4 is added to a 10mL syringe, which is fixed with a needle nozzle. Under conditions of 28℃ room temperature and 20% humidity, the distance between the needle and receiver is set to 15cm, the voltage to 15kV, the syringe advance speed to 3.5mL / hour, and the take-up drum rotation speed to 90r / min. Each rotation speed is used for 10min of receiving time. The electrospun fibers are collected to form the growth-promoting layer. After vacuum drying for 12h, a biodegradable patch with anti-adhesion and growth-promoting properties is obtained. It can be prepared into the required shape and sterilized before use.

[0051] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0052] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A method for preparing a biodegradable patch that prevents adhesion and promotes growth, characterized in that, A biodegradable patch for preventing adhesion and promoting growth comprises an anti-adhesion layer, a polydopamine layer, and a growth-promoting layer connected in sequence. Both the anti-adhesion layer and the growth-promoting layer contain biodegradable polymers, specifically one or more of polyhydroxyalkanoates, polylactic acid, and polycaprolactone. The purity of each of the polyhydroxyalkanoates, polylactic acid, and polycaprolactone is greater than 99.5%, and their molecular weights are all between 80 and 250 kJ. The fiber pore size of the anti-adhesion layer is 5-30 μm, and the fiber pore size of the growth-promoting layer is 150-250 μm. The anti-adhesion layer is composed of the biodegradable polymer, and the growth-promoting layer is composed of the biodegradable polymer and collagen; The anti-adhesion layer and the growth-promoting layer are prepared by electrospinning technology, and the polydopamine layer is prepared by surface self-assembly technology. The preparation method includes the following steps: Step S1: Dissolve the biodegradable polymer in an organic solvent to obtain an electrospinning working solution, wherein the concentration of the biodegradable polymer in the working solution is 8-18% g / mL; Step S2: Use the working solution prepared in step S1 for electrospinning. The spinning environment temperature is 30-40℃ and the humidity is 20-50% to prepare an anti-adhesion layer. Step S3: After drying the anti-adhesion layer prepared in step S2, a dense polydopamine layer is coated on its surface to complete the chemical surface modification of the anti-adhesion layer. Step S4: Prepare a working solution in another container according to the method in step S1. Add collagen fibers to the working solution and change the diameter and pore size of the spun fibers. Add a growth-promoting layer to one side of the polydopamine layer of the anti-adhesion layer. After drying, obtain the anti-adhesion and growth-promoting biodegradable patch. The collagen concentration in the working solution after adding collagen fibers is 1-8% g / mL. In step S2, the take-up drum speed for electrospinning is 30-60 r / min, and in step S4, the take-up drum speed for electrospinning is 90-150 r / min.

2. The preparation method according to claim 1, characterized in that, The organic solvent mentioned in step S1 is one or more of dichloromethane, trichloromethane, and N,N-dimethylformamide.

3. The preparation method according to claim 1, characterized in that, The self-assembly process of the anti-adhesion layer surface in step S3 is as follows: Step S31: Rinse the anti-adhesion layer in deionized water; Step S32: Dissolve dopamine in Tris-HCl buffer solution with a pH of 7.0-8.5 to obtain a dopamine buffer solution with a concentration of 1-3 g / L; Step S33: Immerse the anti-adhesion layer in the dopamine buffer solution and react for 4-12 h. Then remove, clean, and dry to obtain a modified anti-adhesion layer with a polydopamine layer attached to the surface.

4. The application of the anti-adhesion and growth-promoting biodegradable patch prepared by the preparation method according to claim 1 in the preparation of cell scaffolds and soft tissue repair materials.

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