A high-performance graphene-like carbon composite biological patch and its preparation method and application

Abstract

The present invention belongs to the field of biomaterial technology, and discloses a high-performance graphene-like carbon composite biological patch, wherein the composite biological patch comprises a biological patch body and a graphene-like carbon layer coated on the surface of the biological patch body. The composite biological patch prepared by the present invention has the advantages of good mechanical properties, biocompatibility, chemical stability, and slow degradation rate, and is suitable for use as a biological patch material for pelvic floor reconstruction surgery during surgical treatment of pelvic organ prolapse.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomaterials, and in particular relates to a high-performance graphene-like carbon composite biological patch and a preparation method and application thereof. Background Art

[0002] Biological patch is a thin film material and is an indispensable material for surgical treatment of thin-layer tissue damage in the human body. For example, pelvic organ prolapse is a common pelvic floor dysfunction disease that seriously affects the quality of life of patients. With the aging of the population, the incidence rate increases year by year. According to statistics, nearly 50% of women have varying degrees of pelvic organ prolapse (Hong MK and Ding DC, 2019). For moderate to severe pelvic organ prolapse, the use of biological patch pelvic floor reconstruction surgery is the main method of treatment.

[0003] At present, pelvic floor reconstruction surgery using biological patches includes autologous tissue repair, implantation of polypropylene synthetic mesh, and implantation of biological patches. However, autologous tissue repair surgery uses the patient's own tissue for suture reinforcement, but due to the weakness of the patient's own tissue, the recurrence rate is as high as 30%-50% (LoTS, et al., 2015); polypropylene synthetic mesh implantation has good mechanical properties and a low recurrence rate. However, because it is non-absorbable, polypropylene synthetic mesh has complications such as erosion, exposure, infection, contracture, and pain, which are controversial internationally. About half of the countries have banned the use of implanted synthetic meshes (Transvaginalmesh, TVM).

[0004] Biogenic patch implants, such as porcine small intestinal submucosa patch (SIS), basement membrane (BM), acellular dermal matrix patch (ADM), etc., are natural biological skeletons that retain the three-dimensional framework structure of the extracellular matrix (ECM) of the source tissue, which is conducive to cell adhesion, proliferation and differentiation. During the degradation of the patch, it is regulated by cytokines to induce endogenous tissue regeneration and tissue remodeling, thereby repairing defects (Amanda L. Merriman and Michael J. Kennelly, 2020). In 2001, the US FDA approved the use of biological patches in pelvic organ prolapse surgery (Powers SA et al., 2019). Biological patches have good tissue compatibility and are used in pelvic floor reconstruction surgery during the surgical treatment of pelvic organ prolapse. They have great potential as biological patch materials.

[0005] Although biological patches have good tissue compatibility, there are still a series of problems, such as poor mechanical properties, insufficient strength, and self-degradation faster than induced tissue remodeling, resulting in an imbalance in "degradation-remodeling", poor anatomical reduction of the implant site, and recurrence of pelvic organ prolapse, which seriously affect their application effect.

[0006] Therefore, it is an urgent problem for those skilled in the art to provide a biological patch material with good mechanical properties, good biocompatibility, good chemical stability, slow degradation rate, strong induction regeneration ability and the like. Summary of the invention

[0007] In view of this, the present invention provides a high-performance graphene-like carbon composite biological patch and a preparation method and application thereof.

[0008] In order to achieve the above object, the present invention adopts the following technical solution:

[0009] A high-performance graphene-like carbon composite biological patch comprises a biological patch body and a graphene-like carbon layer coated on the surface of the biological patch body.

[0010] The biological patch is linked to the surface hydroxylated graphene-like carbon through hydrogen bonds to achieve an organic combination of the two, thus solving the technical problems existing in the biological patch in the prior art.

[0011] Preferably, the biological patch includes a porcine small intestinal submucosa patch (SIS), a basement membrane (BM), a dermal acellular matrix patch (Acellular dermal matrix, ADM) and other biologically derived patches.

[0012] Preferably, the graphene-like carbon surface in the graphene-like carbon layer is subjected to hydroxylation modification treatment.

[0013] Graphite materials have good biomedical properties, excellent mechanical properties and biocompatibility, high specific strength, high fracture strength, fatigue resistance, friction resistance, excellent anti-thrombotic properties and biological stability. The oxygen-containing groups on the surface of graphene-like carbon and the carboxyl groups remaining on the surface of graphene can produce hydrogen bonds with some polar compounds or polymers to achieve modification. Carbon graphite materials are easy to sterilize and disinfect, and the elastic modulus matches the bone well. They are used as medical implants without absorption, infection, immune response and dissolution.

[0014] Preferably, the hydroxylation modification treatment is polyvinyl alcohol modification.

[0015] Polyvinyl alcohol modification is adopted, and the polyvinyl alcohol aqueous solution has good film-forming properties. Polyvinyl alcohol is an organic compound with a "head-tail" structure in the molecule, which provides a large number of active groups. It is non-toxic and odorless, non-irritating to human skin, and safe and environmentally friendly.

[0016] Preferably, the graphene-like carbon in the graphene-like carbon layer is prepared by oxidation and reduction of graphene.

[0017] Preferably, the biological patch in the biological patch body is modified by soaking in peracetic acid, reacting with polyvinyl alcohol, and forming a film by solution casting, and the graphene-like carbon and the biological patch are linked by its "head-tail" structure and active group grafting to obtain a high-performance graphene-like carbon composite biological patch.

[0018] The high-performance graphene-like carbon composite biological patch prepared by the present invention has good mechanical properties, biocompatibility, chemical stability, and a slow degradation rate. The biological patch is suitable for use as a biological patch material for pelvic floor reconstruction surgery during surgical treatment of pelvic organ prolapse. The present invention links the biological patch with the surface hydroxylated graphene-like carbon through hydrogen bonds to achieve an organic combination of the two, thereby preparing a new high-performance graphene-like carbon composite biological patch material and a graphene-like carbon biological scaffold material.

[0019] The present invention solves the problem of low mechanical properties of biological patches, and the prepared high-performance graphene-like carbon composite biological patch material breaks through the technology of low mechanical properties of biological patches; the present invention solves the problem of weakened performance of existing biological patches after a period of use, and the prepared high-performance graphene-like carbon composite biological patch material changes the technology of weakened performance of existing biological patches after a period of use.

[0020] The above-mentioned method for preparing a high-performance graphene-like carbon composite biological patch comprises the following specific steps:

[0021] (1) Preparation of modified graphene-like carbon: adding a polyvinyl alcohol aqueous solution to a graphene-like carbon dispersion to obtain a polyvinyl alcohol-modified graphene-like carbon dispersion for later use;

[0022] (2) The polyvinyl alcohol-modified graphene-like carbon dispersion is coated on a biological patch soaked in peracetic acid and then dried to obtain a high-performance graphene-like carbon composite biological patch.

[0023] The preparation method of the present invention introduces a graphene-like carbon atomic layer into a biological patch material, and the graphene-like carbon is organically combined with the biological patch. The introduced graphene layer has excellent biocompatibility, excellent anti-thrombotic property and biological stability, is easy to sterilize and disinfect, and is used as an implant without absorption, infection, immune response and dissolution. The present invention has a simple process, a simple flow, is easy to operate, and the raw materials are easily available and low in cost.

[0024] Preferably, the concentration of the polyvinyl alcohol aqueous solution in step (1) is 1-20%;

[0025] The present invention adopts polyvinyl alcohol to modify graphene carbon. The polyvinyl alcohol (PVA17-88) aqueous solution can be formed into polyvinyl alcohol film by solution casting and drying method. The method is non-toxic and tasteless, has no irritation to human skin, and is safe and environmentally friendly.

[0026] The preparation method of the graphene carbon dispersion is as follows: adding graphene carbon into deionized water, ultrasonically treating for 1 hour, and obtaining a uniform graphene carbon dispersion; the volume ratio of the graphene carbon to the deionized water is 1:(1-100);

[0027] The volume ratio of the polyvinyl alcohol aqueous solution to the graphene carbon is 2:1.

[0028] Preferably, the treatment conditions in step (1) are: keeping warm at 80° C. for 1 h at a rotation speed of 300 rpm, and then ultrasonically treating for 30 min.

[0029] Preferably, the coating in step (2) is performed using vacuum coating technology.

[0030] Preferably, the vacuum degree of the vacuum coating technology is (-0.09)-(-0.1)Mpa.

[0031] Preferably, the concentration of peracetic acid used in the peracetic acid soaking in step (2) is 0.2%, and the soaking time is 1 min.

[0032] The invention adopts peracetic acid to modify the biological patch, and adopts peracetic acid solution to soak the biological patch so that the biological patch is not only modified but also sterilized.

[0033] Preferably, the drying conditions in step (2) are: drying at 40-80° C. for 12-24 hours.

[0034] Application of the graphene-like carbon composite biological patch described above or the graphene-like carbon composite biological patch prepared by the preparation method described above in pelvic organ repair products.

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] The composite biological patch prepared by the invention has the advantages of good mechanical properties, biocompatibility, chemical stability and slow degradation rate, and is suitable for being used as a biological patch material for pelvic floor reconstruction surgery during surgical treatment of pelvic organ prolapse. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.

[0038] Figure 1 This is a process flow chart of preparing a high-performance graphene-like carbon composite biological patch according to an embodiment of the present invention;

[0039] Figure 2 This is a structural diagram of the high-performance graphene-like carbon composite biological patch of the present invention. DETAILED DESCRIPTION

[0040] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0041] Example 1

[0042] like Figure 1 A method for preparing a high-performance graphene-like carbon composite biological patch comprises the following specific steps:

[0043] (1) adding graphene oxide to deionized water at a volume ratio of 1:100, and treating with ultrasound (power 150 W) for 1 hour to obtain a uniform graphene oxide dispersion; adding 8% polyvinyl alcohol aqueous solution to the graphene oxide dispersion at a volume ratio of 8% polyvinyl alcohol aqueous solution to graphene oxide of 2:1, stirring and heating (stirring speed 300 rpm), keeping warm at 70°C for 1 hour, and treating with ultrasound (power 150 W) for 30 minutes to obtain a polyvinyl alcohol-modified graphene oxide dispersion; soaking a biological patch in 0.2% peracetic acid solution for 1 minute, and then drying it naturally to obtain a biological patch soaked in peracetic acid, the biological patch is a pig small intestinal submucosa patch (Smallintestinal submucosa, SIS) (a single-layer SIS patch prepared by Zhuoruan Medical Technology (Suzhou) Co., Ltd., with a tensile strength of 5-8 N / cm), and set aside;

[0044] (2) using vacuum coating technology to coat the polyvinyl alcohol-modified graphene oxide dispersion on the biological patch soaked in peracetic acid, with a vacuum degree of -0.09 MPa, and then drying at 60°C for 20 hours to obtain a high-performance graphene-like carbon composite biological patch material; Figure 21 is the relevant structure of the product, wherein 1 is the biological patch body, 2 is the peracetic acid layer, 3 is the hydrogen bond, 4 is the polyvinyl alcohol layer, and 5 is the graphene oxide layer;

[0045] Among them, the biomechanical properties of the prepared product according to performance test analysis are: tensile strength 100N / cm, bursting strength 160N, suture strength 28N, and tear strength 5N.

[0046] Example 2

[0047] like Figure 1 A method for preparing a high-performance graphene-like carbon composite biological patch comprises the following specific steps:

[0048] (1) adding graphene oxide to deionized water at a volume ratio of 1:100, and treating with ultrasound (power 150 W) for 1 hour to obtain a uniform graphene oxide dispersion; adding 8% polyvinyl alcohol aqueous solution to the graphene oxide dispersion at a volume ratio of 8% polyvinyl alcohol aqueous solution to graphene oxide of 2:1, stirring and heating (stirring speed 300 rpm), keeping warm at 80° C. for 1 hour, and treating with ultrasound (power 150 W) for 30 minutes to obtain a polyvinyl alcohol-modified graphene oxide dispersion; soaking a biological patch in 0.2% peracetic acid solution for 1 minute, and then drying it naturally to obtain a biological patch soaked in peracetic acid, the biological patch is a pig small intestinal submucosa patch (Smallintestinal submucosa, SIS), and set aside;

[0049] (2) using vacuum coating technology to coat a polyvinyl alcohol-modified graphene oxide dispersion on a biological patch soaked in peracetic acid, with a vacuum degree of -0.1 MPa, and then drying at 60°C for 20 hours to obtain a high-performance graphene-like carbon composite biological patch material;

[0050] Among them, the biomechanical properties of the prepared product according to performance test analysis are: tensile strength 110N / cm, bursting strength 160N, suture strength 30N, and tear strength 5N.

[0051] Example 3

[0052] like Figure 1 A method for preparing a high-performance graphene-like carbon composite biological patch comprises the following specific steps:

[0053] (1) adding graphene oxide to deionized water at a volume ratio of 1:100, and treating with ultrasound (power 150 W) for 1 hour to obtain a uniform graphene oxide dispersion; adding 8% polyvinyl alcohol aqueous solution to the graphene oxide dispersion at a volume ratio of 8% polyvinyl alcohol aqueous solution to graphene oxide of 2:1, stirring and heating (stirring speed 300 rpm), keeping warm at 95° C. for 1 hour, and treating with ultrasound (power 150 W) for 30 minutes to obtain a polyvinyl alcohol-modified graphene oxide dispersion; soaking a biological patch in 0.2% peracetic acid solution for 1 minute, and then drying it naturally to obtain a biological patch soaked in peracetic acid, the biological patch is a pig small intestinal submucosa patch (Smallintestinal submucosa, SIS), and set aside;

[0054] (2) using vacuum coating technology to coat a polyvinyl alcohol-modified graphene oxide dispersion on a biological patch soaked in peracetic acid, with a vacuum degree of -0.09 MPa, and then drying at 50°C for 20 hours to obtain a high-performance graphene-like carbon composite biological patch material;

[0055] Among them, the biomechanical properties of the prepared product according to performance test analysis are: tensile strength 150N / cm, bursting strength 160N, suture strength 27N, and tear strength 5N.

[0056] The various embodiments are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to in detail.

[0057] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A high-performance graphene-like carbon composite biological patch for pelvic organ repair products, characterized in that: The composite biological patch comprises a biological patch body and a graphene-like carbon layer coated on the surface of the biological patch body; The graphene-like carbon surface in the graphene-like carbon layer is subjected to hydroxylation modification, and the hydroxylation modification is polyvinyl alcohol modification; the graphene-like carbon in the graphene-like carbon layer is prepared by oxidation and reduction of graphene; The biological patch is a biologically derived patch, and the biological patch in the biological patch body is modified by soaking in peracetic acid.

2. The method for preparing a high-performance graphene-like carbon composite biological patch for pelvic organ repair products according to claim 1, characterized in that: The specific steps include: (1) Preparation of modified graphene-like carbon: adding a polyvinyl alcohol aqueous solution to a graphene-like carbon dispersion to obtain a polyvinyl alcohol-modified graphene-like carbon dispersion for later use; (2) The polyvinyl alcohol-modified graphene-like carbon dispersion is coated on a biological patch soaked in peracetic acid and then dried to obtain a high-performance graphene-like carbon composite biological patch for pelvic organ repair products.

3. The method for preparing a high-performance graphene-like carbon composite biological patch for pelvic organ repair products according to claim 2, characterized in that: The concentration of the polyvinyl alcohol aqueous solution in step (1) is 8%; The preparation method of the graphene carbon dispersion is as follows: adding graphene carbon into deionized water, ultrasonically treating for 1 hour, and obtaining a uniform graphene carbon dispersion; the volume ratio of the graphene carbon to the deionized water is 1: (1-100); The volume ratio of the polyvinyl alcohol aqueous solution to the graphene-like carbon is (2-80):

1.

4. The method for preparing a high-performance graphene-like carbon composite biological patch for pelvic organ repair products according to claim 2, characterized in that: The treatment conditions in step (1) are: keeping warm at 80°C for 1 hour at a rotation speed of 300 rpm, and then ultrasonically treating for 30 minutes.

5. The method for preparing a high-performance graphene-like carbon composite biological patch for pelvic organ repair products according to claim 2, characterized in that: The coating in step (2) adopts vacuum coating technology; The concentration of peracetic acid used in the peracetic acid soaking in step (2) is 0.2%, and the soaking time is 1 minute.

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