CN114887119A - High-molecular artificial dura mater with anti-infection capacity and preparation method thereof - Google Patents

High-molecular artificial dura mater with anti-infection capacity and preparation method thereof Download PDF

Info

Publication number
CN114887119A
CN114887119A CN202210499224.6A CN202210499224A CN114887119A CN 114887119 A CN114887119 A CN 114887119A CN 202210499224 A CN202210499224 A CN 202210499224A CN 114887119 A CN114887119 A CN 114887119A
Authority
CN
China
Prior art keywords
dura mater
polylactic acid
double
artificial dura
polytetrafluoroethylene membrane
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202210499224.6A
Other languages
Chinese (zh)
Inventor
潘剑威
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
First Affiliated Hospital of Zhejiang University School of Medicine
Original Assignee
First Affiliated Hospital of Zhejiang University School of Medicine
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by First Affiliated Hospital of Zhejiang University School of Medicine filed Critical First Affiliated Hospital of Zhejiang University School of Medicine
Priority to CN202210499224.6A priority Critical patent/CN114887119A/en
Publication of CN114887119A publication Critical patent/CN114887119A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/16Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/18Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/406Antibiotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602Type of release, e.g. controlled, sustained, slow
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606Coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/04Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/06Coatings containing a mixture of two or more compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/08Coatings comprising two or more layers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/32Materials or treatment for tissue regeneration for nerve reconstruction

Abstract

The invention relates to a high-molecular artificial dura mater with anti-infection capacity and a preparation method thereof, the artificial dura mater is composed of a double-layer expanded polytetrafluoroethylene membrane and a polylactic acid-antibiotic drug coating, wherein the double-layer expanded polytetrafluoroethylene membrane comprises an anti-adhesion layer and a cell adhesion layer: the anti-adhesion layer faces inwards, and the pore diameter is less than 3 micrometers; the cell adhesion layer faces outwards, the pore diameter is more than 10 microns, and the polylactic acid-antibiotic medicine coating is adhered to the inner surface and the outer surface of the double-layer expanded polytetrafluoroethylene membrane. The artificial dura mater has thickness, elasticity and tensile strength similar to those of dura mater, can prevent cerebrospinal fluid leakage and cortical adhesion, and has the characteristics of no toxicity, no immunogenicity, good biocompatibility and no disease infection. The artificial dura mater slowly releases antibiotics in the decomposition process of polylactic acid besides the short-term quick release of surface antibiotics, so that a durable perimembranous antibiotic microenvironment is formed, and the occurrence of infection after meningeal repair surgery can be reduced.

Description

High-molecular artificial dura mater with anti-infection capacity and preparation method thereof
Technical Field
The invention relates to the technical field of biomedicine, in particular to a high-molecular artificial dura mater with anti-infection capacity and a preparation method thereof.
Background
Dura mater is a thick and tough double-layer fibrous membrane that has the effect of protecting the brain and spinal cord. The dural defect is usually caused by trauma and craniocerebral operation, and the dural defect needs to be repaired to prevent cerebrospinal fluid leakage and brain bulging, and the complications of subcutaneous hydrops, cortical adhesion, intracranial infection and the like need to be avoided. The materials currently used for repairing the dura mater are mainly materials of autologous or biological origin, including collagen, cellulose membranes, pericardium, and the like, and various synthetic materials including metal materials, silicone rubber, polyester, polyethylene, and the like.
The ideal meningeal repair material needs to have certain elasticity and stability to prevent cerebrospinal fluid leakage and cortical adhesion, and also has the characteristics of no toxicity, no immunogenicity, good biocompatibility and no disease infection. However, all current meningeal repair materials have certain drawbacks. Although the autologous fascia meets all the requirements, the autologous fascia has limited material resources, is easy to damage the original tissue structure, is easy to cause adhesion and causes postoperative epilepsy. Although widely used, materials of biological origin such as bovine pericardium pose potential risks in terms of immunogenicity, disease transmission, etc. and are prone to cortical adhesions; collagen also has the problem of immunological rejection, and is easy to absorb after being repaired, thereby being difficult to play the role of isolating cortex and subcutaneous tissues for a long time and being not beneficial to skull repair. In the artificially synthesized high polymer material, the absorbable material cannot complete the meningitis of the defect area before the material is absorbed due to the limited growth capacity of the meninges, so the absorbable material cannot be well applied to clinic; among the non-absorbable materials, only a few materials such as polytetrafluoroethylene can meet the requirements at present in consideration of the performance, stability and safety of the artificial meninges, but the single-layer polytetrafluoroethylene membrane widely used in clinic still has the problems that cells and fibers back to the meningeal surface are difficult to attach, and effusion, postoperative infection and the like are easy to occur.
In addition, control of craniocerebral surgical infections is often achieved through prophylactic intravenous use of antibiotics, but current infection rates are still as high as around 4% and are difficult to control once infection occurs, even with many patients dying from postoperative intracranial infections. Because of the blood brain barrier, a plurality of medicines can not kill intracranial bacteria, the medicines which can be selected by intravenous administration after infection is limited, and meanwhile, the meninges repairing material plays a role of a bacterial culture medium, so once infection occurs after meninges repairing, the control is extremely difficult, and sometimes even the artificial meninges needs to be removed by re-operation. The existing artificial meninges do not contain antibiotics generally, the possibility of infection after meninges repair is obviously higher than that of autologous fascia repair, and the infection is difficult to control.
The existence of the problems limits the use of the artificial meninges to a great extent, so that patients cannot be treated well. Under the condition, the artificial meninges have the thickness, the elasticity and the tensile capacity similar to those of the dura mater, can prevent cerebrospinal fluid leakage and cortical adhesion, have the characteristics of no toxicity, no immunogenicity, good biocompatibility and no disease infection, can form a lasting perimembranous antibiotic microenvironment, and can reduce the occurrence of infection after meningeal repair operation, and are particularly important.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a high-molecular artificial dura mater with anti-infection capacity and a preparation method thereof. The artificial dura mater comprises a double-layer expanded polytetrafluoroethylene membrane anti-adhesion layer, a double-layer expanded polytetrafluoroethylene membrane cell adhesion layer, a polylactic acid-antibiotic drug coating inner covering layer and a polylactic acid-antibiotic drug coating outer covering layer. The artificial dura mater consists of a double-layer expanded polytetrafluoroethylene membrane, has the thickness, the elasticity and the tensile capacity similar to those of the dura mater, and can prevent cerebrospinal fluid leakage and cortical adhesion; meanwhile, the medicine has the characteristics of no toxicity, no immunogenicity, good biocompatibility and no disease infection. The artificial dura mater is also provided with a polylactic acid-antibiotic drug coating, and besides short-term and rapid release of surface antibiotics, antibiotics can be slowly released in the polylactic acid decomposition process, so that a durable perimembranous antibiotic microenvironment is formed, and the occurrence of infection after meningeal repair surgery can be reduced.
The invention achieves the aim through the following technical scheme: the utility model provides an artificial dura mater of polymer that possesses anti infectious capacity, comprises double-deck popped polytetrafluoroethylene membrane, and polylactic acid-antibiotic medicine coating, double-deck popped polytetrafluoroethylene membrane include anti-adhesion layer, cell adhesion layer, anti-adhesion layer inwards, the aperture is less than 3 microns, cell adhesion layer outwards, the aperture is more than 10 microns, polylactic acid-antibiotic medicine coating is attached to double-deck popped polytetrafluoroethylene membrane internal and external surface.
The preparation method of the artificial dura mater comprises the following steps:
(1) preparing a puffed polytetrafluoroethylene membrane with the pore diameter of less than 3 microns as an anti-adhesion layer;
(2) preparing a puffed polytetrafluoroethylene membrane with the pore diameter of more than 10 microns as a cell adhesion layer;
(3) bonding the double-layer film by adopting a hot pressing technology;
(4) dissolving polylactic acid in ethyl acetate to prepare a polylactic acid-ethyl acetate solvent system;
(5) adding antibiotics into a polylactic acid-ethyl acetate solvent system according to a proportion to prepare a uniform phase mixed solution;
(6) and immersing the double-layer expanded polytetrafluoroethylene membrane in the mixed solution for 10 minutes, taking out and airing, repeating the process for three times, and forming a polylactic acid-antibiotic coating on the surface of the membrane after the solvent is volatilized.
Preferably, the thickness of the double layer expanded polytetrafluoroethylene film is 0.25 microns.
Preferably, the fiber diameter of the double layer expanded polytetrafluoroethylene membrane is between 2 and 10 microns.
Preferably, the medicament is any one antibiotic or a mixture of several antibiotics.
Preferably, the hot pressing technology in the step (3) has the process conditions of 2.5MPa and 350 ℃.
Preferably, the double-layer film in the step (3) is subjected to hot-press bonding, a transition zone is formed in the middle of the double-layer film, and the diameter of the transition zone is controlled to be less than 1 micron.
Preferably, the polylactic acid-ethyl acetate solvent system of step (4) is prepared by using 1.0g of polylactic acid and 10ml of ethyl acetate as solvent.
Preferably, the homogeneous mixed solution in the step (5) is a 5% homogeneous mixed solution.
Preferably, the preparation process of the preparation method is carried out under aseptic conditions.
The invention has the beneficial effects that:
(1) the parameters of thickness, elasticity, tensile property and leakage-proof property of the double-layer expanded polytetrafluoroethylene membrane are compared with those of human meninges, and the double-layer expanded polytetrafluoroethylene membrane is prepared by taking the parameters of the human meninges as a standard.
(2) The invention has a double-layer membrane structure of expanded polytetrafluoroethylene, the inner layer is an anti-adhesion layer, the aperture is below 3 microns, and the adhesion of the cortex can be effectively prevented; the outer layer is a cell adhesion layer, the aperture is more than 10 microns, the fibroblast is favorably adhered to and secretes collagen fibers and elastic fibers, the formation of extramembranous dead space is avoided, and the subcutaneous effusion and the infection probability are reduced. The material does not contain any components of biological origin and has no exogenous cells and proteins, so that the risks of immunological rejection and disease transmission are avoided.
(3) The invention simultaneously uses polylactic acid-antibiotic drug coating technology to uniformly distribute antibiotics such as gentamicin/rifampicin and the like on the surface of the expanded polytetrafluoroethylene membrane, the antibiotics on the surface are quickly released in a short period after the artificial meninges is placed in a body, and the rest antibiotics are further slowly released along with the decomposition of polylactic acid to generate a continuous membrane-surrounding antibiotic microenvironment; compared with a pure expanded polytetrafluoroethylene membrane, the method can effectively reduce the occurrence of intracranial infection after meningeal repair.
(4) The invention also utilizes the hot-pressing adhesion technology to prepare the double-layer polytetrafluoroethylene membrane, avoids using other materials as an adhesive layer, and ensures the material unicity, biological safety and stability; meanwhile, the middle transition zone with the aperture smaller than 1 micron can effectively prevent the outer layer fiber from entering the inner layer through the membrane pores.
(5) The expanded polytetrafluoroethylene membrane material has sufficient sources, short production time, simple storage and transportation, easy control of product quality, easy realization of production standard, and realization of low-cost and high-efficiency industrial production.
Drawings
FIG. 1 is a schematic cross-sectional view of the present invention;
in the figure: 1 represents an adhesion-preventing layer, 2 represents a cell adhesion layer, and 3 and 4 represent polylactic acid-antibiotic drug coatings.
Detailed Description
The present invention will be described below with reference to specific examples, but the present invention is not limited thereto.
Example 1: the antibiotic is dissolved in a polylactic acid-ethyl acetate solvent system to prepare a mixed solution, and a coating is formed on the surface of the double-layer expanded polytetrafluoroethylene membrane by a solution casting method. The coating can select different types of antibiotics according to specific conditions, and can be selected from cephalosporins, sulfonamides, quinolones, cephamycins and the like. The whole preparation process is carried out in an aseptic state, and the prepared artificial dura mater is stored after being cleaned, sterilized and packaged.
Example 2: this example differs from example 1 in that the polylactic acid-antibiotic drug coating is no longer applied after the bilayer membrane has been bonded using the hot pressing technique.
Example 3: the difference between this example and example 1 is that, because most of the intracranial infections after meningeal repair are gram-positive bacteria such as staphylococcus aureus, and the like, in combination with the ability of antibiotics to penetrate the blood brain barrier and the effectiveness of current clinical antibiotic use on intracranial infections, the antibiotic selected by the polylactic acid-antibiotic drug coating is gentamicin, and the polylactic acid-antibiotic drug coating is a polylactic acid-gentamicin coating.
Example 4: this example differs from example 3 in that the antibiotic selected for the polylactic acid-antibiotic drug coating is rifampin, which is a polylactic acid-rifampin coating.
Example 5: this example differs from the above examples in that the dura mater prepared in examples 1, 2, 3, 4 was used for the leakage prevention test: the dura mater is passed through with a small gauge round needle with 4-0 silk thread, leaving a 4-0 silk thread 1 cm long at the needle hole. Placing the prepared dura mater with silk threads in a leakage tester, wherein one side of the dura mater is air under normal air pressure, and the other side of the dura mater is normal-pressure pure water; the pressure is gradually increased on the pure water side, and the pressure is recorded when the pure water leaks to the air side, namely the osmotic pressure.
Example 6: this example differs from the previous examples in that the dura mater prepared in examples 1, 2, 3 and 4 was used for in vitro bacteriostasis tests: culturing Staphylococcus aureus in blood plate at 37 deg.C for 18 hr to logarithmic growth phase, preparing into bacterial suspension with physiological saline, and adjusting bacterial concentration to 1.5 × 10 by spectrophotometry 8 cfu/ml, then 0.5ml of the suspension was spread evenly on agar medium to make assay plates. 10 each of the artificial meninges samples of example 3 and example 4 were randomly selected, placed on a staphylococcus aureus agar plate, incubated at 37 ℃ for 24 hours in an incubator, and then the diameter of the zone of inhibition was measured and the artificial meninges samples of example 1 and example 2 were used as negative control tests.
Example 7: this example differs from the above examples in that the present example carried out a new zealand rabbit animal experiment using the dura mater prepared in example 2: the number of the experimental animals is 5. Animals were anesthetized by intramuscular ketamine injection and shaved and placed on a dedicated operating table. 2% iodine tincture and 75% alcohol. The scalp is longitudinally cut in the middle of the top of the animal head, the periosteum is separated by a stripper, skull plates at two tops are exposed, the skull is ground by a high-speed grinding drill, bone windows are formed at the tops of two sides, rectangular dura mater with the size of 3 cm multiplied by 3 cm at the tops of two sides is cut by small scissors, and partial dura mater defects are manufactured. The skin was electrocauterized on the exposed surface of the skin, resulting in 6 lesion spots of 1 micron by 1 micron size. The artificial meninges prepared in the embodiment 2 of the invention is trimmed into the repairing material with corresponding shape and size, the anti-adhesion layer faces the surface of the brain, 4-0 no-damage silk threads are used for intermittent sewing, the needle pitch is 4 microns, and the defect of the meninges at the top of the rabbit is repaired. The muscle was sutured with round needle 4 gauge silk.
Animals were routinely fed and observed post-operatively: the post-operation animal has good recovery, the incision has good healing, no cerebrospinal fluid leakage and no epilepsia. After operation, the food and water intake is normal, the dyskinesia is avoided, and the survival time is up to the predetermined period. After 15 months of operation, the animal takes the operation position as the center, and the specimen is cut within 1 cm of the operation position, so that the specimen comprises the artificial meninges, the peripheral dura mater and the brain tissue on the inner surface. After the scalp is opened, the subcutaneous tissue and the surface of the artificial dura mater are found to be adhered but not tight; the fibroblast and collagen fiber are observed to grow into the surface of the meninges under a microscope, but the rejection reaction such as bleeding does not exist. The joint of the artificial meninges and the dura mater is flat, the connective tissue is completely covered, and no gap exists; the inner surface of the artificial meninges is smooth and has no adhesion with the surface of the cerebral cortex.
Example 8: this example differs from the above examples in that it was subjected to a new zealand rabbit animal experiment using the dura mater prepared in example 1: the experimental animals are not limited to 5 male and female animals. Animals were anesthetized by intramuscular ketamine injection and shaved and placed on a dedicated operating table. 2% iodine tincture and 75% alcohol. The scalp is longitudinally cut in the middle of the top of the animal head, the periosteum is separated by a stripper, skull plates at two tops are exposed, the skull is ground by a telling burr, a bone window is formed at the tops of two sides, rectangular dura mater with the size of 3 cm multiplied by 3 cm at the tops of two sides is cut by small scissors, and partial dura mater defects are manufactured. The exposed skin surface was electrocauterized, resulting in 6 lesion spots of 1 micron by 1 micron size. The artificial meninges prepared in the embodiment 1 of the invention is trimmed into the repairing material with corresponding shape and size, the anti-adhesion layer faces the surface of the brain, 4-0 no-damage silk threads are used for intermittent sewing, the needle pitch is 4 microns, and the defect of the meninges at the top of the rabbit is repaired. The muscle was sutured with round needle 4 gauge silk.
Animals were routinely fed and observed post-operatively: the post-operation animal has good recovery, the incision has good healing, no cerebrospinal fluid leakage and no epilepsia. After operation, the food and water intake is normal, the dyskinesia is avoided, and the survival time is up to the predetermined period. After 15 months of operation, the animal takes the operation position as the center, and the specimen is cut within 1 cm of the operation position, so that the specimen comprises the artificial meninges, the peripheral dura mater and the brain tissue on the inner surface. After the scalp is opened, the subcutaneous tissue and the surface of the artificial dura mater are found to be adhered but not tight; the fibroblast and collagen fiber are observed to grow into the surface of the meninges under a microscope, but the rejection reaction such as bleeding does not exist. The joint of the artificial meninges and the dura mater is flat, the connective tissue is completely covered, and no gap exists; the inner surface of the artificial meninges is smooth and has no adhesion with the surface of the cerebral cortex. The inner surface and the outer surface of the artificial meninges are observed by a scanning electron microscope to find that the polylactic acid coating completely disappears.
Example 9: this example differs from the previous examples in that it was subjected to a new zealand group animal experiment using the dura mater prepared in examples 1, 3, 4: 30 New Zealand rabbits were divided into three groups of 10 rabbits each. A model of meningeal defects was created as in example 6 and repaired with the dura mater prepared in examples 1, 3, and 4. The first group of repairs used the artificial dura mater prepared in example 1, the second group used the artificial dura mater prepared in example 3, and the third group used the artificial dura mater prepared in example 4.
And (4) postoperative observation: intracranial infections occurred in 2 animals within four weeks after surgery in the first group. No intracranial infection occurred in the second and third groups of experimental animals at four weeks after the operation. After 15 months of operation, the animal takes the operation position as the center, and cuts a specimen within the range of 1 cm larger than the operation position, so that the specimen comprises the artificial meninges, the peripheral dura mater and the brain tissue on the inner surface. After the scalp is opened, the subcutaneous tissue and the surface of the artificial dura mater are adhered but not tight in three groups; the fibroblast and collagen fiber are observed to grow into the surface of the meninges under a microscope, but the rejection reaction such as bleeding does not exist. The joint of the artificial meninges and the dura mater is flat, the connective tissue is completely covered, and no gap exists; the inner surface of the artificial meninges is smooth and has no adhesion with the surface of the cerebral cortex.
While the invention has been described in connection with specific embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.

Claims (10)

1. A polymer artificial dura mater with anti-infection ability, comprising: double-deck popped polytetrafluoroethylene membrane, polylactic acid-antibiotic medicine coating (3), (4), double-deck popped polytetrafluoroethylene membrane include anti-adhesion layer (1), cell adhesion layer (2), anti-adhesion layer (1) inwards, the aperture is below 3 microns, cell adhesion layer (2) outwards, the aperture is more than 10 microns, polylactic acid-antibiotic medicine coating (3), (4) are attached to double-deck popped polytetrafluoroethylene membrane internal and external surface.
2. The artificial dura mater with anti-infective activity of claim 1, wherein the expanded polytetrafluoroethylene membrane has a layer thickness of 0.25 μm.
3. The polymer artificial dura mater according to claim 1, wherein the diameter of the expanded polytetrafluoroethylene membrane is 2-10 μm.
4. The polymer artificial dura mater according to claim 1, wherein the drug is any one antibiotic or a mixture of several antibiotics.
5. A method for preparing the polymer artificial dura mater with anti-infective ability of any one of claims 1 to 4, comprising the steps of:
(1) preparing a puffed polytetrafluoroethylene membrane with the pore diameter of less than 3 microns as an anti-adhesion layer (1);
(2) preparing a swelling polytetrafluoroethylene membrane with the aperture of more than 10 microns as a cell attachment layer (2);
(3) bonding the double-layer film by adopting a hot pressing technology;
(4) dissolving polylactic acid in ethyl acetate to prepare a polylactic acid-ethyl acetate solvent system;
(5) adding antibiotics into a polylactic acid-ethyl acetate solvent system according to a proportion to prepare a uniform phase mixed solution;
(6) and (3) immersing the double-layer expanded polytetrafluoroethylene membrane in the mixed solution for 10 minutes, taking out and airing, repeating the process for three times, and forming polylactic acid-antibiotic coatings (3) and (4) on the membrane surface after the solvent is volatilized.
6. The method for preparing the polymer artificial dura mater with anti-infective ability according to claim 5, wherein the hot pressing technique in the step (3) is performed under the process conditions of 2.5MPa and 350 ℃.
7. The method for preparing the artificial polymer dura mater with anti-infection ability according to claim 5, wherein the double-layer film in the step (3) is subjected to hot-press bonding, a transition zone is formed in the middle of the double-layer film, and the diameter of the transition zone is controlled to be less than 1 micron.
8. The method for preparing polymer artificial dura mater with anti-infective ability according to claim 5, wherein the solvent amount of the polylactic acid-ethyl acetate solvent system in the step (4) is 1.0g of polylactic acid and 10ml of ethyl acetate.
9. The method for preparing polymer artificial dura mater with anti-infective ability according to claim 5, wherein the homogeneous mixed solution in the step (5) is a 5% homogeneous mixed solution.
10. The method for preparing polymer artificial dura mater with anti-infective ability according to any one of claims 5 to 9, wherein the preparation process is performed under aseptic conditions.
CN202210499224.6A 2022-05-09 2022-05-09 High-molecular artificial dura mater with anti-infection capacity and preparation method thereof Pending CN114887119A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210499224.6A CN114887119A (en) 2022-05-09 2022-05-09 High-molecular artificial dura mater with anti-infection capacity and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210499224.6A CN114887119A (en) 2022-05-09 2022-05-09 High-molecular artificial dura mater with anti-infection capacity and preparation method thereof

Publications (1)

Publication Number Publication Date
CN114887119A true CN114887119A (en) 2022-08-12

Family

ID=82722616

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210499224.6A Pending CN114887119A (en) 2022-05-09 2022-05-09 High-molecular artificial dura mater with anti-infection capacity and preparation method thereof

Country Status (1)

Country Link
CN (1) CN114887119A (en)

Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN2418880Y (en) * 2000-04-11 2001-02-14 李建民 Absorbing composite laminated materials for resoration of dura mater of brain
CN1317297A (en) * 2000-04-11 2001-10-17 张保军 Absorbable artificial dura meter of brain and its preparing process
CN101559242A (en) * 2009-05-22 2009-10-21 广州迈普再生医学科技有限公司 Nano artificial dura mater capable of being used as medicine sustained-release system and preparation method thereof
CN201814903U (en) * 2010-10-22 2011-05-04 上海索康医用材料有限公司 Surgical anti-adhesion membrane
CN102698319A (en) * 2012-03-02 2012-10-03 首都医科大学附属北京朝阳医院 Anti-tumor biological patch
CN103418031A (en) * 2012-05-17 2013-12-04 天津市康尔医疗器械有限公司 Absorbable endocranium healing patch and preparation method thereof
CN103656749A (en) * 2013-12-10 2014-03-26 北华大学 Composite degradable antibacterial artificial cerebral dura mater and preparation method thereof
CN103800942A (en) * 2012-11-14 2014-05-21 深圳迈普再生医学科技有限公司 Pelvic floor repairing sheet
WO2014075388A1 (en) * 2012-11-14 2014-05-22 广州迈普再生医学科技有限公司 Fiber membranes for repairing tissue and products and preparation method thereof
CN105343931A (en) * 2015-11-27 2016-02-24 广州迈普再生医学科技有限公司 Fibrous membrane for tissue repair and its preparation method, composite fibrous membrane for tissue repair, and their uses
CN106668935A (en) * 2016-11-22 2017-05-17 大博医疗科技股份有限公司 Expanded polytetrafluoroethylene artificial dura mater and preparation technique thereof
CN106901866A (en) * 2015-12-22 2017-06-30 上海典范医疗科技有限公司 Compound dural patch for preventing adhesion and preparation method thereof
US20180193519A1 (en) * 2017-01-12 2018-07-12 Beijing Bonsci Technology Co., Ltd. Composite dura substitute implant
CN109364294A (en) * 2018-11-27 2019-02-22 普丽妍(南京)医疗科技有限公司 A kind of adsorbable artificial endocranium and preparation method thereof
CN109939268A (en) * 2019-03-21 2019-06-28 中山大学 A kind of antiseptic anti-adhesion sticking patch and the preparation method and application thereof
CN111420123A (en) * 2020-03-16 2020-07-17 江西光至金辉医疗制品有限公司 Degradable anti-adhesion double-layer dura mater patch and preparation method thereof
CN113663137A (en) * 2021-08-19 2021-11-19 北京邦塞科技有限公司 Composite biological patch and preparation method and application thereof
CN114288476A (en) * 2022-01-05 2022-04-08 奥精医疗科技股份有限公司 Artificial dura mater and preparation method thereof

Patent Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN2418880Y (en) * 2000-04-11 2001-02-14 李建民 Absorbing composite laminated materials for resoration of dura mater of brain
CN1317297A (en) * 2000-04-11 2001-10-17 张保军 Absorbable artificial dura meter of brain and its preparing process
CN101559242A (en) * 2009-05-22 2009-10-21 广州迈普再生医学科技有限公司 Nano artificial dura mater capable of being used as medicine sustained-release system and preparation method thereof
CN201814903U (en) * 2010-10-22 2011-05-04 上海索康医用材料有限公司 Surgical anti-adhesion membrane
CN102698319A (en) * 2012-03-02 2012-10-03 首都医科大学附属北京朝阳医院 Anti-tumor biological patch
CN103418031A (en) * 2012-05-17 2013-12-04 天津市康尔医疗器械有限公司 Absorbable endocranium healing patch and preparation method thereof
WO2014075388A1 (en) * 2012-11-14 2014-05-22 广州迈普再生医学科技有限公司 Fiber membranes for repairing tissue and products and preparation method thereof
CN103800942A (en) * 2012-11-14 2014-05-21 深圳迈普再生医学科技有限公司 Pelvic floor repairing sheet
CN103656749A (en) * 2013-12-10 2014-03-26 北华大学 Composite degradable antibacterial artificial cerebral dura mater and preparation method thereof
CN105343931A (en) * 2015-11-27 2016-02-24 广州迈普再生医学科技有限公司 Fibrous membrane for tissue repair and its preparation method, composite fibrous membrane for tissue repair, and their uses
CN106901866A (en) * 2015-12-22 2017-06-30 上海典范医疗科技有限公司 Compound dural patch for preventing adhesion and preparation method thereof
CN106668935A (en) * 2016-11-22 2017-05-17 大博医疗科技股份有限公司 Expanded polytetrafluoroethylene artificial dura mater and preparation technique thereof
US20180193519A1 (en) * 2017-01-12 2018-07-12 Beijing Bonsci Technology Co., Ltd. Composite dura substitute implant
CN109364294A (en) * 2018-11-27 2019-02-22 普丽妍(南京)医疗科技有限公司 A kind of adsorbable artificial endocranium and preparation method thereof
CN109939268A (en) * 2019-03-21 2019-06-28 中山大学 A kind of antiseptic anti-adhesion sticking patch and the preparation method and application thereof
CN111420123A (en) * 2020-03-16 2020-07-17 江西光至金辉医疗制品有限公司 Degradable anti-adhesion double-layer dura mater patch and preparation method thereof
CN113663137A (en) * 2021-08-19 2021-11-19 北京邦塞科技有限公司 Composite biological patch and preparation method and application thereof
CN114288476A (en) * 2022-01-05 2022-04-08 奥精医疗科技股份有限公司 Artificial dura mater and preparation method thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
王琼: "抗菌疝修复补片与创伤修复的研究" *

Similar Documents

Publication Publication Date Title
US9271822B2 (en) Artificial dura mater and manufacturing method thereof
US6977231B1 (en) Suturable adhesion-preventing membrane
CA2525405C (en) Compositions for repairing and regenerating human dura mater
Lee et al. Experimental evaluation of silicone-coated Dacron and collagen fabric-film laminate as dural substitutes
US20190046689A1 (en) Wet-Electrospun Biodegradable Scaffold and Uses Therefor
US20160175487A1 (en) Tissue repair scaffold and preparation method and purpose thereof
US10046088B2 (en) Nanoscale collagen particles and membranes
Pogorielov et al. Experimental evaluation of new chitin–chitosan graft for duraplasty
CN104248777A (en) Tissue repair support and its preparation method and use
US20050107876A1 (en) Dermal substitute consisting of amnion and biodegradable polymer, the preparation method and the use thereof
Filippi et al. Tightness of duraplasty in rabbits: a comparative study
EP3223872B1 (en) Artificial biomembrane using silk matrix and method of manufacturing the same
CN114887119A (en) High-molecular artificial dura mater with anti-infection capacity and preparation method thereof
RU2491962C1 (en) Transplant for scleroplasty (versions)
US20180264170A1 (en) Vascular patch using silk matrix and method of manufacturing the same
DE19948120A1 (en) 3D matrix for the production of cell transplants
CN114425102A (en) Hydrophilic electrostatic spinning implant for inducing skin tissue regeneration
CN109045347B (en) Degradable drug-loaded hemostatic microsphere and preparation method thereof
CN107648671B (en) Multilayer anti-infection high-strength artificial dura mater and preparation method thereof
RU2519103C2 (en) Bioresorbable hydrogel polymer composition with biologically active substances (versions)
US10195158B2 (en) Bioactive oil based polyesteramide nanofibers for wound healing applications
Kuevda et al. Application of recellularized non-woven materials from collagen-enriched polylactide for creation of tissue-engineered diaphragm constructs
Al Fauzi et al. Bovine Pericardium-Chitosan As A Biomaterial Prospect For Substitute and Accelerate Tissue Healing of Dural Defect: A Review
CN117018283A (en) Multi-layer nano-fiber artificial dura mater using polyaryletherketone as substrate and preparation method thereof
CN116607266A (en) Asymmetric nanofiber membrane containing giant salamander skin secretion and preparation method and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20220812

WD01 Invention patent application deemed withdrawn after publication