WO2018121630A1 - Feuille de réparation de tissu composite et procédé de préparation et application s'y rapportant - Google Patents

Feuille de réparation de tissu composite et procédé de préparation et application s'y rapportant Download PDF

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WO2018121630A1
WO2018121630A1 PCT/CN2017/119133 CN2017119133W WO2018121630A1 WO 2018121630 A1 WO2018121630 A1 WO 2018121630A1 CN 2017119133 W CN2017119133 W CN 2017119133W WO 2018121630 A1 WO2018121630 A1 WO 2018121630A1
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Prior art keywords
solution
tissue repair
repair patch
composite tissue
woven mesh
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PCT/CN2017/119133
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English (en)
Chinese (zh)
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李林静
邓坤学
袁玉宇
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广州迈普再生医学科技有限公司
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Publication of WO2018121630A1 publication Critical patent/WO2018121630A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/0063—Implantable repair or support meshes, e.g. hernia meshes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/20—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/222—Gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/34—Materials or treatment for tissue regeneration for soft tissue reconstruction

Definitions

  • the present disclosure relates to a composite tissue repair patch and a preparation method and application thereof, and belongs to the field of implanted medical materials.
  • tissue repair patches include woven mesh and electrospun nanofiber membranes.
  • the woven mesh has good mechanical properties and can provide sufficient mechanical support.
  • the woven mesh sheet has problems such as high hardness, rough surface, and adhesion to tissues, it is difficult to obtain an ideal repairing effect.
  • Electrospun nanofiber membrane has the characteristics of large specific surface area, high porosity and high surface energy. It can be used as a porous scaffold for cell growth and promote cell migration. It also has a three-dimensional porous structure, which is easy to transport nutrients and oxygen to facilitate cells. Proliferation and differentiation. Therefore, the electrospun nanofiber membrane has good tissue repair properties. However, the mechanical strength of the electrospun nanofiber membrane is weak and cannot be directly applied to tissue repair (such as helium repair) where the mechanical strength is required to be high.
  • the combination of the woven mesh sheet and the electrospun nanofiber membrane mainly includes hot pressing, welding, bonding or receiving the nanofiber filament on the woven mesh sheet.
  • hot pressing and welding require higher temperature, the processing process is difficult to control, and it is easy to destroy the structure of the woven mesh or the electrospun nanofiber membrane.
  • the adhesion of the adhesive to the material of the adhesive is poorly compatible with the tissue, easily adheres to the tissue, and the strength of the bond is low.
  • the treatment method of directly receiving nanofibers on woven mesh sheets is not strong (Chen Yanchun et al. Preparation and performance of PP/PLA pelvic composite patch [J], Journal of Donghua University (Natural Science Edition), 2014, 40 (6): 687-691), it is easy to stratify in clinical use, and the effect of repair cannot be achieved.
  • the patent application document CN105435309A discloses a composite patch of an electrospun film and a woven mesh sheet which is obtained by heat-compression bonding using an adhesive layer having a lower melting point.
  • the melting point of the adhesive layer material used must be much lower than the melting point of the electrospinning film layer material to prevent the structure of the electrospinning film layer from being destroyed during the subsequent hot pressing process, and the composite process is complicated, and the composite patch is The porosity is small.
  • the present disclosure provides a composite tissue repair patch and a preparation method and application thereof.
  • the composite tissue repair patch of the present disclosure effectively combines the nanofiber membrane and the woven mesh sheet by using a suitable adhesive material, so that the composite tissue repair patch not only has good mechanical properties, but also provides sufficient mechanical support, and Has good biocompatibility.
  • the present disclosure also provides a method for preparing a composite tissue repair patch, which not only retains the characteristics of the original structure of the nanofiber membrane, but also improves the biocompatibility of the woven mesh sheet.
  • the present disclosure provides a composite tissue repair patch comprising:
  • nanofiber film a nanofiber film, a woven mesh sheet, and an adhesive material, wherein the adhesive material is located between the nanofiber film and the woven mesh sheet;
  • the adhesion material includes a hydrophilic substance, the nanofiber membrane and the woven mesh sheet are combined by the adhesion material, and the adhesion material is embedded in the pores of the nanofiber membrane and the woven mesh sheet ;
  • the peeling strength between the nanofiber membrane and the woven mesh sheet is 20 to 75 cN/mm; the breaking strength of the composite tissue repair patch is 8 to 12.5 MPa; preferably, the composite tissue repairing patch The elongation at break is 20 to 250%; more preferably, the composite tissue repair patch has a porosity of 50 to 90%.
  • a composite tissue repair patch according to the present disclosure wherein the composite tissue repair patch further comprises an anti-adhesion layer adhered to a face of the woven mesh opposite the side on which the nanofiber membrane is located.
  • the hydrophilic substance has a weight average molecular weight of 50,000 to 2,000,000 Da.
  • the hydrophilic substance includes: a nitrogen-containing compound and a derivative thereof, a cellulose compound and a derivative thereof, an alcohol compound and a derivative thereof, a chitosan compound, and One or more of its derivatives, saccharide compounds and derivatives thereof.
  • the nitrogen-containing compound includes a proteinaceous compound, preferably one or both of collagen and gelatin; and the chitosan compound comprises: carboxymethyl chitosan One or two of hydroxypropyl chitosan; the cellulose compound includes one or both of carboxymethyl cellulose and sodium carboxymethyl cellulose.
  • the hydrophilic substance comprises a modified hydrophilic substance, preferably comprising a hydrophilic substance modified by a crosslinking agent.
  • the distance between the nanofiber membrane and the woven mesh sheet is 0.1 to 3 mm; preferably 0.2 to 2 mm.
  • the nanofiber membrane is produced by a method including an electrospinning step.
  • the nanofiber membrane is interwoven from filaments having a diameter of 10 nm to 100 ⁇ m, preferably the filament is made of a degradable material, and more preferably, the degradable Materials include polylactic acid, poly-DL-lactic acid, polycaprolactone, polyhydroxyalkanoate, polyglycolide, poly-lactide; collagen, gelatin, chitosan, hyaluronic acid, cellulose One or more.
  • the degradable Materials include polylactic acid, poly-DL-lactic acid, polycaprolactone, polyhydroxyalkanoate, polyglycolide, poly-lactide; collagen, gelatin, chitosan, hyaluronic acid, cellulose One or more.
  • the nanofiber membrane is loaded with a drug, preferably comprising a growth factor; more preferably comprising one or both of an epidermal growth factor, a fibroblast growth factor.
  • the woven mesh sheet being made of a non-degradable material, preferably, the non-degradable material comprises polypropylene, polyvinylidene fluoride, polyethylene terephthalate And one or more of expanded polytetrafluoroethylene.
  • the present disclosure also provides a method of preparing a composite tissue repair patch according to the present disclosure, comprising:
  • a composite step preparing an adhesive material solution, and compounding the nanofiber membrane and the woven mesh sheet with the adhesive material solution to obtain the composite tissue repair patch;
  • the nanofiber membrane is compounded with the woven mesh sheet by a freeze drying process, a coating process or a casting process using the adhesion material solution.
  • An anti-blocking solution layer is formed on the opposite side of the side on which the fiber membrane is located.
  • the freeze drying process comprises the following steps:
  • the woven mesh sheet is laid flat on the adhesive material solution, and the composite tissue repair patch is obtained by freeze drying.
  • the thickness of the solution of the adhesive material is 0.1 to 3 mm, preferably 0.2 to 2 mm; the time of the standing is 1 to 24 hours, preferably 3 to 6 hours; the adhesion material
  • the concentration of the adhesive material in the solution is 0.1-20%, preferably 5-15%; preferably, the freeze-drying process has a pre-freezing temperature of -80 to -10 ° C, preferably -80 to -50 ° C; The drying temperature is -20 to 30 ° C, preferably -10 to 25 ° C.
  • the hydrophilic substance in the freeze-drying process, includes a cellulose compound and/or a derivative thereof, preferably including hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl methyl group.
  • a cellulose compound and/or a derivative thereof preferably including hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl methyl group.
  • the hydrophilic substance comprises a modified cellulose compound and/or a derivative thereof, preferably comprising modified hydroxyethyl cellulose, carboxymethyl One or more of cellulose, hydroxypropyl methylcellulose.
  • the modifying treatment includes a step of performing a crosslinking reaction using a crosslinking agent; preferably, the crosslinking agent includes an aldehyde compound, preferably including formaldehyde, acetaldehyde One or more of glutaraldehyde, more preferably glutaraldehyde.
  • the crosslinking agent includes an aldehyde compound, preferably including formaldehyde, acetaldehyde One or more of glutaraldehyde, more preferably glutaraldehyde.
  • the modifying treatment further comprises: performing a crosslinking reaction in a salt solution; preferably, the salt includes a neutral salt, and more preferably, the neutral salt It is one or more of water-soluble aluminum salts, sodium salts, calcium salts and iron salts.
  • the modification treatment is carried out in a solution, and preferably, the pH of the solution is acidic.
  • the temperature of the modification treatment is 50-130 ° C, preferably 60-80 ° C; the modification treatment time is 20-240 min, preferably 40-80 min;
  • the hydrophilic substance has a mass concentration of 0.1 to 20%, preferably 5 to 15%.
  • the coating process includes the following steps:
  • the woven mesh sheet is tiled on the adhesive material solution and evaporated to dryness to obtain the composite tissue repair patch.
  • the thickness of the solution of the adhesive material is 0.1 to 3 mm, preferably 1 to 2 mm; the time of the standing is 1 to 72 hours, preferably 24 to 48 hours; the adhesion In the material solution, the mass concentration of the adhesion material is from 1 to 50%, preferably from 10 to 20%.
  • the hydrophilic substance includes a proteinaceous compound and/or a derivative thereof, preferably one or both of collagen and gelatin;
  • the hydrophilic substance comprises a modified protein compound, preferably one or both of modified modified collagen and gelatin.
  • the modifying treatment includes a step of performing a crosslinking reaction using a crosslinking agent; preferably, the crosslinking agent includes a carbodiimide/N-hydroxysuccinyl group One or more of the imine, genipin, and an aldehyde compound, preferably including one or both of carbodiimide, carbodiimide/N-hydroxysuccinimide, more preferably including carbonized secondary Amine/N-hydroxysuccinimide.
  • the temperature of the modification treatment is 10 to 70 ° C, preferably 25 to 50 ° C; the modification treatment time is 1 to 72 h, preferably 12 to 72 h;
  • the hydrophilic substance has a mass of 1 to 50%, preferably 10 to 20%.
  • the casting process includes the following steps:
  • the adhesive material solution is cast on the woven mesh sheet and allowed to stand, and evaporated to obtain the composite tissue repair patch.
  • the thickness of the solution of the adhesive material is 0.1 to 3 mm, preferably 1 to 2 mm; the treatment time of the standing is 1 to 72 hours, preferably 24 to 48 hours; In the material solution, the mass concentration of the adhesion material is from 0.1 to 20%, preferably from 5 to 15%.
  • the hydrophilic substance in the casting process, includes a chitosan compound and/or a derivative thereof, preferably one of carboxymethyl chitosan and hydroxypropyl chitosan. Species or two;
  • the hydrophilic substance comprises a modified chitosan compound, preferably one or both of modified modified carboxymethyl chitosan, hydroxypropyl chitosan.
  • the modifying treatment includes a step of performing a crosslinking reaction using a crosslinking agent; preferably, the crosslinking agent includes glycerin and water; preferably, the The volume ratio of glycerol to water is from 0.1 to 5:1, preferably from 0.5 to 2:1.
  • the temperature of the modification treatment is 10 to 50 ° C, preferably 20 to 30 ° C; the modification treatment time is 1 to 48 h, preferably 12 to 24 h;
  • the hydrophilic substance has a mass concentration of 0.1 to 20%, preferably 5 to 15%.
  • the present disclosure also provides a composite tissue repair patch according to the present disclosure in preparing a hernia repair patch, a pelvic floor repair patch, a urinary incontinence suspension strap, a rotator cuff repair patch, a breast patch, a wound repair patch, and a hernia repair.
  • the application in the patch is not limited to a hernia repair patch, a pelvic floor repair patch, a urinary incontinence suspension strap, a rotator cuff repair patch, a breast patch, a wound repair patch, and a hernia repair.
  • the composite tissue repair patch of the present disclosure is not easy to be layered, and has good mechanical properties and soft properties.
  • the composite tissue repair patch of the present disclosure is also capable of mimicking the natural extracellular matrix from the nanometer scale, and can serve as a porous scaffold for cell growth, promoting regeneration of new tissues and blood vessels.
  • the method for preparing a composite tissue repair patch of the present disclosure is simple, does not affect and change the original structure of the nanofiber membrane, and better preserves the characteristics of the original porous three-dimensional network structure of the nanofiber membrane.
  • Example 1 is a schematic structural view of a composite tissue repair patch prepared in Example 1 of the present disclosure
  • Example 2 is a schematic structural view of a composite tissue repair patch prepared in Example 2 of the present disclosure
  • Example 3 is a photograph of a composite tissue repair patch prepared in Example 2 of the present disclosure after repairing a hernia repair operation;
  • Example 4 is a photograph of a composite tissue repair patch prepared in Example 4 of the present disclosure after repairing a hernia repair operation;
  • Figure 5 is a photograph of a hernia repair after repair with a woven mesh
  • Figure 6 is a diagram showing the repair effect of the composite tissue repair patch prepared in Example 2 for two weeks after the hernia repair operation;
  • Example 7 is a view showing the repair effect of the composite tissue repair patch prepared in Example 4 for two weeks after the hernia repair operation;
  • Fig. 8 is a view showing the effect of repairing two weeks after the hernia repair operation using the woven mesh.
  • the present disclosure provides a composite tissue repair patch comprising: a nanofiber membrane, a woven mesh, and an adhesive material, wherein the adhesive material is between the nanofiber membrane and the woven mesh.
  • the adhesion material comprises a hydrophilic substance, preferably comprising a degradable hydrophilic substance; the nanofiber membrane and the woven mesh sheet are combined by the adhesion material, and the adhesion material is embedded in the nanofiber membrane The layers and the pores of the woven mesh layer.
  • the peeling strength between the nanofiber membrane and the woven mesh sheet is 20 to 75 cN/mm; the breaking strength of the composite tissue repair patch is 8 to 12.5 MPa; preferably, the composite tissue repairing patch The elongation at break is 20 to 250%; more preferably, the composite tissue repair patch has a porosity of 50 to 90%.
  • the hydrophilic substance may be a hydrophilic natural substance and/or a derivative thereof, a modified hydrophilic natural substance and/or a derivative thereof, and some hydrophilic non-natural substances.
  • the effective compounding of the nanofiber membrane and the woven mesh by the adhesive material not only does not affect the original structure of the nanofiber membrane and the woven mesh, retains the characteristics of the original structure of the nanofiber membrane and the woven mesh, and also promotes the tissue. , repair and regeneration of blood vessels.
  • the adhesive material is embedded in the pores of the nanofiber membrane and the woven mesh sheet, so that the nanofiber membrane and the woven mesh sheet are tightly bonded together, so that the prepared composite tissue repair patch has high peeling. Strength and breaking strength enable tissue repair in areas where high mechanical strength is required.
  • hydrophilic substances in particular hydrophilic natural substances and / or their derivatives or modified hydrophilic natural substances and / or their derivatives as adhesion materials, can be rapidly degraded, and can also make nanofiber membranes It is tightly bonded to the woven mesh.
  • the composite tissue repair patch according to the present disclosure further includes an anti-adhesion layer adhered to a face of the woven mesh opposite the side on which the nanofiber film is located.
  • the face of the woven mesh opposite the side on which the nanofiber membrane is located means the side of the woven mesh that is remote from the nanofiber membrane. Therefore, the composite repair patch can not only promote tissue growth and repair, but also can play an anti-adhesion function, which is beneficial to prevent the composite tissue repair patch and the organ adhesion and the patch shrinkage, etc., and can effectively reduce the patient's Complications such as persistent pain or partial loss of function in the surgical site are a multifunctional composite tissue repair patch.
  • the nanofiber membrane has a three-dimensional porous structure, a large specific surface area, a high porosity and a high surface energy, and can be used as a porous scaffold for cell growth, promotes cell migration and proliferation, and has a three-dimensional porous structure of a nanofiber membrane. It is easier to transport nutrients and oxygen, which is more conducive to cell proliferation and differentiation.
  • the biocompatibility of the woven mesh sheet can be further improved by using the adhesive material to form a film on the surface of the woven mesh sheet.
  • a composite tissue repair patch according to the present disclosure wherein the hydrophilic substance has a weight average molecular weight of 50,000 to 2,000,000 Da.
  • a composite tissue repairing patch according to the present disclosure wherein the hydrophilic substance comprises: a nitrogen-containing compound and a derivative thereof, a cellulose compound and a derivative thereof, an alcohol compound and a derivative thereof, and a chitosan One or more of a compound and a derivative thereof, a saccharide compound, and a derivative thereof; preferably, one or more of the above-mentioned hydrophilic substances after the modification treatment.
  • a composite tissue repair patch according to the present disclosure wherein the nitrogen-containing compound comprises a proteinaceous compound such as one or both of collagen and gelatin; and the chitosan compound comprises: a carboxymethyl shell One or two of a polysaccharide, hydroxypropyl chitosan; and the cellulose compound includes one or both of carboxymethylcellulose and sodium carboxymethylcellulose.
  • the nitrogen-containing compound comprises a proteinaceous compound such as one or both of collagen and gelatin
  • the chitosan compound comprises: a carboxymethyl shell One or two of a polysaccharide, hydroxypropyl chitosan
  • the cellulose compound includes one or both of carboxymethylcellulose and sodium carboxymethylcellulose.
  • a composite tissue repair patch according to the present disclosure wherein a distance between the nanofiber membrane and the woven mesh sheet is 0.1 to 3 mm; preferably 0.2 to 2 mm, that is, sandwiched between the nanofiber membrane and the woven mesh sheet
  • the thickness of the adhesive material is 0.1 to 3 mm; preferably 0.2 to 2 mm.
  • the distance between the nanofiber membrane and the woven mesh can be determined by randomly taking a plurality of points (for example, 3 points) using a measuring instrument (for example, a scale).
  • the thickness of the adhesive material is related to factors such as the molecular weight of the adhesive material, the thickness of the adhesive material solution, and the concentration of the adhesive material in the adhesive material solution. For example, when the thickness of the adhesion material solution is thin and the concentration of the adhesion material in the adhesion material solution is low, the thickness of the adhesion material is also thin; when the thickness of the adhesion material solution is thick and the concentration of the adhesion material in the adhesion material solution is When higher, the thickness of the adhesive material also becomes thicker.
  • the adhesion material is too thin, resulting in a slightly poor peel strength, affecting the composite effect of the material; if the distance between the nanofiber membrane and the woven mesh sheet is greater than 3 mm, then The adhesion material is too thick, which affects the biocompatibility of the composite patch to the tissue.
  • the thickness of the solution of the adhesive material described in the present disclosure refers to the thickness of the solution of the adhesive material sandwiched between the nanofiber membrane and the woven mesh sheet.
  • the composite tissue repair patch according to the present disclosure wherein the composite tissue repair patch has an overall thickness of 0.3 to 5 mm; preferably 0.5 to 3 mm.
  • nanofiber membrane is produced by a method including electrospinning, of course, the nanofiber membrane is also commercially available.
  • the present disclosure provides a method of electrospinning, specifically comprising the following steps:
  • the polymer solution was placed in an electrospinning syringe, electrospun, to obtain a fiber filament, and the fiber filament was received into a film-like structure to obtain a nanofiber membrane.
  • the solvent comprises one or more of trifluoroethanol, hexafluoroisopropanol, trifluoroacetic acid, cyclohexanone, acetone, methyl ethyl ketone, tetrahydrofuran, chloroform, glacial acetic acid, formic acid, propionic acid, and water.
  • the rate of adjusting the micro syringe pump is 0.1-15 mL/h
  • the voltage of the high voltage generator is adjusted to 10 to 35 kV
  • the receiving distance of the receiving device is 5-30 cm.
  • a tissue repair patch according to the present disclosure wherein the nanofiber membrane is interwoven by filaments having a diameter of 10 nm to 100 ⁇ m.
  • the degradable material comprises polylactic acid (PLA), poly-L-lactic acid (PLLA), poly-DL-lactic acid (PDLLA), polycaprolactone (PCL), polyhydroxyalkanoate (PHA), polyethyl b.
  • an anti-adhesion tissue repair patch wherein the nanofiber membrane is loaded with a drug, preferably comprising a growth factor; more preferably comprising one or both of an epidermal growth factor, a fibroblast growth factor .
  • the composite tissue repair patch can also serve as a carrier for drugs, which can reduce drug degradation and loss, reduce side effects, and improve bioavailability.
  • Growth factor refers to a class of peptide molecules that regulate cell growth by binding to cell membrane-specific receptors. By loading growth factors, the repair patch can accelerate cell growth by suturing the wound tissue. Promote wound healing.
  • a composite tissue repair patch according to the present disclosure wherein the woven mesh sheet is made of a non-degradable material, preferably, the non-degradable material comprises polypropylene, polyvinylidene fluoride, polyethylene terephthalate One or more of an alcohol ester and a expanded polytetrafluoroethylene.
  • the present disclosure also provides a method of preparing a composite tissue repair patch according to the present disclosure, comprising:
  • a compounding step of preparing an adhesion material solution, compounding the nanofiber membrane and the woven mesh sheet with the adhesion material solution to obtain the composite tissue repair patch preferably, by a freeze drying process or a coating process or casting The process recombines the nanofiber membrane with the woven mesh sheet with the solution of the adherent material.
  • a molecular weight of the adhesion material and/or a concentration of the adhesion material solution is adjusted such that the adhesion material solution overflows from the pores of the woven mesh sheet and is in the woven mesh sheet
  • An anti-blocking solution layer is formed on the surface opposite to the side on which the nanofiber membrane is located.
  • the woven mesh sheet may be immersed in the adhesive material solution by controlling the molecular weight of the adhesive material and/or the concentration of the adhesive material solution, that is, on the side of the woven mesh sheet opposite to the side of the nanofiber membrane.
  • An anti-blocking solution layer is formed on the surface to form an anti-blocking film on the surface of the woven mesh sheet opposite to the side on which the nanofiber film is located after drying.
  • freeze-drying process comprises the following steps:
  • the woven mesh sheet is laid on the adhesive material solution, and freeze-dried to obtain a composite tissue repair patch.
  • the adhesive material solution overflows from the pores of the woven mesh sheet and forms an anti-blocking solution layer on a surface of the woven mesh sheet opposite to the side where the nanofiber membrane is located, and freeze-dried to obtain a composite tissue repairing patch.
  • a sheet; the composite tissue repair patch having an anti-adhesion layer on a side of the woven mesh opposite the side on which the nanofiber membrane is located.
  • the hydrophilic substance comprises a cellulose compound and/or a base derivative, preferably one or more of hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl methyl cellulose;
  • the hydrophilic substance comprises a modified cellulose compound/or a derivative thereof; further preferably, the hydrophilic substance comprises a modified hydroxyethyl cellulose, a carboxymethyl group One or more of cellulose, hydroxypropyl methylcellulose.
  • the standing time is from 1 to 24 h, preferably from 3 to 6 h.
  • the time of adhering the solution of the adhesive material on the nanofiber membrane is in the range of 1 to 24 hours, the solution of the adhesive material can be evenly distributed on the surface of the nanofiber membrane, and the solution of the adhesive material is embedded in the nanofiber membrane. In the pores, the contact area between the molecules and the molecules is increased, thereby increasing the binding force between the adhesion material solution and the nanofiber membrane.
  • the mass concentration of the adhesive material is 0.1 to 20%; preferably 5 to 15%, and the thickness of the solution of the adhesive material is 0.1 to 3 mm, preferably 0.2 to 2 mm.
  • the modifying treatment includes a step of performing a crosslinking reaction using a crosslinking agent; preferably, the crosslinking agent includes an aldehyde compound, preferably including one of formaldehyde, acetaldehyde, and glutaraldehyde. One or more, more preferably including glutaraldehyde.
  • glutaraldehyde is used as the crosslinking agent in the present disclosure, the toxicity to the living body is relatively small, and when reacted with the protein, the activity is high, the reaction is fast, the binding amount is high, the crosslinking property is good, and the product is stable.
  • the modifying treatment further comprises: performing a crosslinking reaction in a salt solution; preferably, the salt includes a neutral salt, and the neutral salt preferably includes a water-soluble aluminum salt, a sodium salt, and a calcium salt.
  • a salt and an iron salt are examples of a salt solution.
  • the modification treatment is carried out in a solution, and the pH of the solution is acidic.
  • the temperature of the modification treatment is 50 to 130 ° C, preferably 60 to 80 ° C.
  • the modification treatment time is 20 to 240 minutes, preferably 40 to 80 minutes; and the mass concentration of the hydrophilic substance in the adhesion material solution is 0.1 to 20%, preferably 5 to 15%.
  • the volume of the crosslinking agent is from 0.1 to 10% by volume, preferably from 0.5 to 5% by volume, based on the mass of the hydrophilic substance.
  • the unit of the volume of the crosslinking agent is mL
  • the unit of the mass of the hydrophilic substance is g.
  • the freeze-drying pre-freezing temperature is -80 to -10 ° C, preferably -80 to -50 ° C; and the drying temperature is -20 to 30 ° C, preferably -10 to 25 ° C.
  • the pre-freezing temperature is between -80 and -10 °C, it is advantageous to form a higher porosity and a more uniform structure, which can increase the specific surface area of the material, thereby making the nanofiber membrane layer and the woven mesh layer effective. integrate.
  • the coating process comprises the following steps:
  • the woven mesh sheet is laid on the adhesive material solution, and after volatilization and drying, the composite tissue repair patch is obtained.
  • the adhesive material solution overflows from the pores of the woven mesh sheet and forms an anti-blocking solution layer on a surface of the woven mesh sheet opposite to the side where the nanofiber membrane is located, and after evaporation and drying, the composite is obtained.
  • the tissue repair patch is made such that the composite tissue repair patch has an anti-adhesion layer on a side of the woven mesh opposite the side on which the nanofiber membrane is located.
  • the hydrophilic substance includes a proteinaceous compound and/or a derivative thereof, and preferably includes one or both of collagen protein and gelatin. More preferably, the hydrophilic substance comprises a modified protein compound and/or a derivative thereof. Further preferably, the hydrophilic substance comprises one or both of modified collagen and gelatin.
  • the thickness of the solution of the adhesive material is 0.1 to 3 mm, preferably 1 to 2 mm; the time of the standing is 1 to 72 hours, preferably 24 to 48 hours; and the mass concentration of the adhesive material in the solution of the adhesive material It is 1 to 50%, preferably 10 to 20%.
  • the adhesion material solution is laid on the nanofiber membrane for a time in the range of 1 to 72 h, the adhesion material solution can be better distributed on the surface of the nanofiber membrane, and the adhesion material solution is embedded in the nanofiber membrane. In the pores, the contact area between the molecules and the molecules is increased, thereby increasing the binding force between the adhesion material solution and the nanofiber membrane.
  • the crosslinking agent used in the modification treatment includes one or more of carbodiimide/N-hydroxysuccinimide, genipin, and an aldehyde compound, and preferably includes carbodiimide and carbonized di One or both of the amine/N-hydroxysuccinimide, more preferably including carbodiimide/N-hydroxysuccinimide.
  • the temperature of the modification treatment is 10 to 70 ° C, preferably 25 to 50 ° C; the modification treatment time is 1 to 72 h, preferably 12 to 72 h; in the adhesion material solution, the pro
  • the mass concentration of the aqueous substance is from 1 to 50%, preferably from 10 to 20%.
  • the mass of the crosslinking agent is 10 to 50%, preferably 10 to 20% by mass of the hydrophilic substance.
  • the casting process comprises the following steps:
  • the adhesive material solution is uniformly cast on the woven mesh sheet and allowed to stand, and the composite tissue repair patch is obtained after volatilization and drying.
  • the adhesive material solution overflows from the pores of the woven mesh sheet and forms an anti-blocking solution layer on a surface of the woven mesh sheet opposite to the side where the nanofiber membrane is located, and the composite tissue is obtained after evaporation and drying. Repair the patch.
  • the composite tissue repair patch is provided with an anti-blocking layer on a side of the woven mesh opposite the side on which the nanofiber membrane is located.
  • the hydrophilic substance includes a chitosan compound and/or a derivative thereof, and preferably includes one or both of carboxymethyl chitosan and hydroxypropyl chitosan. More preferably, the hydrophilic substance includes a modified chitosan compound and/or a derivative thereof. Further preferably, the hydrophilic substance comprises one or both of modified modified carboxymethyl chitosan, hydroxypropyl chitosan.
  • the thickness of the solution of the adhesive material is 0.1 to 3 mm, preferably 1 to 2 mm; the treatment time for the standing is 1 to 72 hours, preferably 24 to 48 hours; in the solution of the adhesive material, the adhesion material The mass concentration is from 0.1 to 20%, preferably from 5 to 15%.
  • the standing time is in the range of 1 to 72 h, the adhesion material solution can be evenly distributed on the surface of the nanofiber membrane, and the adhesion material solution is embedded in the pores of the nanofiber membrane, and the contact between the molecules and the molecules The area is increased to increase the bonding force between the adhesion material solution and the nanofiber membrane.
  • the crosslinking agent used in the modification treatment includes glycerin and water; preferably, the volume ratio of the glycerin to water is 0.1 to 5:1, preferably 0.5 to 2:1.
  • the hydrophilic substance is directly dissolved in a crosslinking agent composed of glycerin and water to form a solution of the adhesion material. In the solution of the adhering material, the hydrophilic substance has a mass concentration of 0.1 to 20%, preferably 5 to 15%.
  • the temperature of the modification treatment is 10 to 50 ° C, preferably 20 to 30 ° C; and the modification treatment time is 1 to 48 h, preferably 12 to 24 h.
  • the solution of the adhesion material obtained by modifying the chitosan compound by glycerin and water is colorless, transparent, smooth and bubble-free.
  • the finally prepared composite tissue repair patch can synergistically enhance the physiological function of the wound site and improve the physical and chemical properties.
  • the composite tissue repair patch of the present disclosure may be a three-layer structure or a multi-layer structure, such as a four-layer structure, a five-layer structure, or the like.
  • the composite tissue repair patch has a five-layer structure, it is preferably composed of a first nanofiber membrane, a first adhesive material, a woven mesh sheet, a second adhesive material, and a second nanofiber membrane.
  • the present disclosure also provides a composite tissue repair patch according to the present disclosure in preparing a hernia repair patch, a pelvic floor repair patch, a urinary incontinence suspension strap, a rotator cuff repair patch, a breast patch, a wound repair patch, and a hernia repair.
  • the application in the patch is not limited to a hernia repair patch, a pelvic floor repair patch, a urinary incontinence suspension strap, a rotator cuff repair patch, a breast patch, a wound repair patch, and a hernia repair.
  • the composite tissue repair patch of the present disclosure tests the peel strength ⁇ T between the nanofiber membrane and the woven mesh sheet by a microcomputer controlled electronic universal material tensile machine (model HY-3080).
  • the specific method is as follows: the microcomputer-controlled electronic universal material tensile machine is clamped on the nanofiber membrane at one end, and the braided mesh is clamped at the other end, and the test gauge is set to 25 mm, the tensile speed is 10 mm/min, and the test size is set to 50 mm ⁇ 15 mm. , tested in parallel 3 times and averaged.
  • the method for determining the breaking strength of the composite tissue repair patch according to the present disclosure is to test the breaking strength of the composite tissue repair patch by a tensile machine.
  • the sample to be tested was cut into a strip structure of 40 mm ⁇ 10 mm, and the thickness (T) of the composite tissue repair patch was measured using a thickness gauge, and the breaking strength (f) and the elongation at break (E) were measured, and the stretching speed was 10 mm. /min, the gauge is 25mm, tested in parallel 3 times, and averaged.
  • the porosity of the composite tissue repair patch was determined by solvent filling method. Ethanol is used as a reagent because ethanol easily penetrates into the interior of the composite tissue repair patch without causing material shrinkage and swelling.
  • the specific measurement method is as follows: in a 100 mL container, an absolute ethanol solution is injected, and the composite tissue repair patch (weight m 1 ) which is dried to balance weight is weighed in ethanol, and the vacuum is vacuumed until the composite tissue repair patch is not Then, the bubble overflows, and the composite tissue repairing patch containing ethanol, the composite tissue repair patch, and the total weight of the beaker is m 2 , and then the internal tissue containing the ethanol is taken out, and the total weight of the beaker and the remaining ethanol is m 3 . Parallel 3 times.
  • the measured porosity P is:
  • (m 2 -m 3 -m 1 ) is the mass of ethanol contained in the pores in the composite tissue repair patch;
  • (m 2 -m 3 ) is the total mass of the composite tissue repair patch containing ethanol.
  • Polylactic acid (PLLA) was dissolved in a hexafluoroisopropanol solution in which the concentration of polylactic acid was 5% (g/mL), and the mixture was stirred to obtain a uniform polymer solution.
  • the polymer solution was placed in an electrospinning syringe, the rate of the micro syringe pump was adjusted to 8 mL/h, the voltage of the high voltage generator was adjusted to 15 kV, and the receiving distance of the receiving device was adjusted to 15 cm, and electrospinning was performed as a film. After the layer thickness reached 0.15 mm, the electrospinning was turned off to obtain a nanofiber membrane.
  • the nanofiber membrane is placed in a container, and then the above adhesive material solution is laid on the nanofiber membrane and allowed to stand for 6 hours.
  • the solution of the adhesive material is uniformly embedded in the pores of the nanofiber membrane, and the thickness of the solution of the adhesive material is controlled to be 1 mm. .
  • the woven mesh sheet is laid on the adhesive material solution, and then pre-frozen in a lyophilizer at a temperature of -80 ° C for 3 h; dried at 25 ° C for 36 h, taken out and stretch molded to obtain a composite as shown in FIG. Tissue repair patch, wherein 1 is a nanofiber membrane, 2 is a woven mesh, and 3 is an adhesive material.
  • PolyDL-lactic acid was dissolved in a hexafluoroisopropanol solution in which the concentration of polyDL-lactic acid was 10% (g/mL), and the mixture was stirred to obtain a uniform polymer solution.
  • the polymer solution was placed in an electrospinning syringe, the rate of the micro syringe pump was adjusted to 7 mL/h, the voltage of the high voltage generator was adjusted to 20 kV, and the receiving distance of the receiving device was adjusted to 15 cm, and electrospinning was performed as a film. After the layer thickness reached 0.2 mm, the electrospinning was turned off to obtain a nanofiber membrane.
  • the nanofiber membrane is placed in a container, and then the above-mentioned adhesive material solution is laid on the nanofiber membrane and allowed to stand for 4 hours.
  • the solution of the adhesive material is uniformly embedded in the pores of the nanofiber membrane, and the thickness of the solution of the adhesive material is controlled to be 1 mm. .
  • the composite tissue repair patch has an anti-blocking layer on a side of the woven mesh opposite the side on which the nanofiber membrane is located.
  • 1 is a nanofiber membrane
  • 2 is a woven mesh
  • 3 is an adhesive material
  • 4 is an anti-blocking layer.
  • Gelatin was dissolved in a trifluoroethanol solution in which the concentration of gelatin was 7% (g/mL), and the mixture was stirred to obtain a uniform polymer solution.
  • the polymer solution was placed in an electrospinning syringe, the rate of the micro syringe pump was adjusted to 5 mL/h, the voltage of the high voltage generator was adjusted to 30 kV, the receiving distance of the receiving device was adjusted to 20 cm, and electrospinning was performed as a film. After the layer thickness reached 0.5 mm, the electrospinning was turned off to obtain a nanofiber membrane.
  • the nanofiber membrane is placed in a container, and then the above-mentioned adhesive material solution is laid on the nanofiber membrane and allowed to stand for 2 hours.
  • the solution of the adhesive material is uniformly embedded in the pores of the nanofiber membrane, and the thickness of the adhesive material solution is controlled to be 0.5. Mm.
  • the composite tissue repair patch has an anti-blocking layer on a side of the woven mesh opposite the side on which the nanofiber membrane is located.
  • Polylactic acid (PLA) was dissolved in a hexafluoroisopropanol solution in which the concentration of polylactic acid was 7% (g/mL), and the mixture was stirred to obtain a uniform polymer solution.
  • the polymer solution was placed in an electrospinning syringe, the rate of the micro syringe pump was adjusted to 15 mL/h, the voltage of the high voltage generator was adjusted to 12 kV, the receiving distance of the receiving device was adjusted to 20 cm, and electrospinning was performed, when the film thickness was After reaching 0.3 mm, the electrospinning was turned off to obtain a nanofiber membrane.
  • the nanofiber membrane is placed in a container, and then the adhesive material solution is uniformly coated on the nanofiber membrane for 24 hours, the solution of the adhesive material is uniformly embedded in the pores of the nanofiber membrane, and the thickness of the solution of the adhesive material is controlled to be 1mm.
  • a woven mesh sheet is tiled onto the adhesive material solution, and the adhesive material overflows from the pores of the woven mesh sheet and forms an anti-blocking solution layer on a side of the woven mesh sheet opposite to the side on which the nanofiber membrane is located.
  • the solvent in the solution to be adhered is evaporated and dried to obtain a composite tissue repair patch.
  • the composite tissue repair patch has an anti-blocking layer on a side of the woven mesh opposite the side on which the nanofiber membrane is located.
  • Polyethylidene-lactide (PLGA) was dissolved in a hexafluoroisopropanol solution in which the concentration of poly-glycolide was 5% (g/mL), and the mixture was stirred to obtain a uniform polymer solution.
  • the polymer solution was placed in an electrospinning syringe, the rate of the micro syringe pump was adjusted to 10 mL/h, the voltage of the high voltage generator was adjusted to 25 kV, the receiving distance of the receiving device was adjusted to 15 cm, and electrospinning was performed, when the film thickness was After reaching 0.5 mm, the electrospinning was turned off to obtain a nanofiber membrane.
  • the nanofiber membrane is placed in a container, and then the adhesive material solution is uniformly coated on the nanofiber membrane, and the standing time is 36 h, the solution of the adhesive material is uniformly embedded in the pores of the nanofiber membrane, and the thickness of the solution of the adhesive material is controlled to be 2mm.
  • the woven mesh is tiled onto the adherent material solution. And the adhesion material solution overflows from the pores of the woven mesh sheet and forms an anti-blocking solution layer on a side of the woven mesh sheet opposite to the side on which the nanofiber membrane is located. After standing under natural conditions, the solvent in the solution to be adhered is evaporated and dried to obtain a composite tissue repair patch.
  • the composite tissue repair patch has an anti-blocking layer on a side of the woven mesh opposite the side on which the nanofiber membrane is located.
  • the polycaprolactone (PCL) is dissolved in a tetrahydrofuran solution, wherein the concentration of the polycaprolactone is 15% (g/mL), and the mixture is stirred to obtain a uniform polymer solution; the polymer solution is charged into the electrospinning syringe.
  • the rate of adjusting the micro-injection pump is 6mL/h, the voltage of the high-voltage generator is adjusted to 20kV, the receiving distance of the receiving device is adjusted to 10cm, and the electrospinning is performed. When the thickness of the film reaches 0.7mm, the electrospinning is turned off to obtain the nanometer. Fiber membrane.
  • the nanofiber membrane is placed in a container and the woven mesh is then laid flat on the nanofiber membrane.
  • the adhesive material solution was cast on the woven mesh sheet, allowed to stand for 24 hours, and the thickness of the adhesive material solution was controlled to be 1.5 mm.
  • the adhesive material solution penetrates the nanofiber membrane through the mesh of the woven mesh. And the adhesive material overflows from the pores of the woven mesh sheet and forms an anti-blocking solution layer on a side of the woven mesh sheet opposite to the side on which the nanofiber membrane is located. Then, under natural conditions, the solvent in the solution to be adhered is evaporated and dried to obtain a composite tissue repair patch.
  • the composite tissue repair patch has an anti-blocking layer on a side of the woven mesh opposite the side on which the nanofiber membrane is located.
  • the hyaluronic acid (HA) is dissolved in water, wherein the concentration of hyaluronic acid is 3% (g/mL), and the mixture is stirred to obtain a uniform polymer solution; the polymer solution is charged into the electrospinning syringe to adjust the microinjection.
  • the pump speed is 3 mL/h, the voltage of the high-voltage generator is adjusted to 35 kV, the receiving distance of the receiving device is adjusted to 10 cm, and electrospinning is performed. When the film thickness reaches 0.2 mm, the electrospinning is turned off to obtain a nanofiber membrane.
  • 3 g of hydroxypropyl chitosan was weighed and dissolved in 100 mL of a mixed solution composed of 50 mL of purified water and 50 mL of glycerin, and stirred to dissolve to obtain a uniform chitosan solution. Then, it was modified at a temperature of 30 ° C for 24 hours to obtain a solution of the adhering material.
  • the nanofiber membrane is placed in a container and the woven mesh is then laid flat on the nanofiber membrane.
  • the adhesive material solution was cast on the woven mesh sheet, allowed to stand for 36 h, and the thickness of the adhesive material solution was controlled to be 2.5 mm.
  • the adhesive material solution penetrates the nanofiber membrane through the mesh of the woven mesh. And the adhesion material overflows from the pores of the woven mesh sheet to form an anti-blocking solution layer on a surface of the woven mesh sheet opposite to the side on which the nanofiber membrane is located. Then, under natural conditions, the solvent in the solution to be adhered is evaporated and dried to obtain a composite tissue repair patch.
  • the composite tissue repair patch has an anti-blocking layer on a side of the woven mesh opposite the side on which the nanofiber membrane is located.
  • the composite tissue repair patch prepared in Examples 1-7 was tested for performance, as shown in Table 1:
  • the composite tissue repair patch prepared in Examples 2 and 4 was subjected to a helium gas repair experiment.
  • New Zealand experimental rabbits were taken for 5 months and weighed 2.5 kg. New Zealand experimental rabbits were randomly divided into 3 groups of 5 New Zealand experimental rabbits. The New Zealand experimental rabbits were anesthetized, prepared for skin and fixed on the wooden board. After disinfection, the skin was cut in the middle of the abdomen, and the skin was cut with a 20# scalpel along the white line of the New Zealand experimental rabbit. The length was about 10 cm and the muscles were exposed. The entire abdominal wall (including peritoneum, muscle, fascia tissue) having a size of 2 cm x 3 cm was excised.
  • the composite tissue repair patch of Example 2 and the composite tissue repair patch of Example 4 and a commercially available woven mesh sheet were respectively used, and the patch was sutured intermittently with the surrounding muscles with a 0# silk thread, and the skin was intermittently sutured by a 4# silk thread.
  • FIG. 3 is a photograph of the composite tissue repair patch prepared by the embodiment 2 of the present disclosure after repairing the hernia repair operation; 4 is a photograph of a composite tissue repair patch prepared in Example 4 of the present disclosure after repairing a hernia repair operation; and FIG. 5 is a photograph of a hernia repair performed by a woven mesh.
  • New Zealand experimental rabbits were routinely observed and fed after surgery. At 2 weeks postoperatively, the repaired parts of New Zealand experimental rabbits were dissected to observe the tissue repair of New Zealand experimental rabbit wounds.
  • FIG. 6 is a view showing the effect of repairing the composite tissue repair patch prepared in Example 2 for two weeks after the hernia repair operation
  • FIG. 7 is a two-week period after the hernia repair operation using the composite tissue repair patch prepared in Example 4.
  • the repair effect picture Figure 8 is the repair effect of the two weeks after the hernia repair operation using the woven mesh.
  • the anatomical results showed that a large number of new blood vessels and tissues were newly added to the composite tissue repair patch of Examples 2 and 4.
  • the surrounding part of the implant site was tightly bound to the blood vessels and tissues; that is, a large number of blood vessels and capillaries were visible inside and around the composite tissue repair patch. Blood vessels, showing good tissue repair effects. Therefore, after the composite tissue repairing patches of Examples 2 and 4 are implanted, the new tissue grows rapidly, and can grow into the composite tissue repair patch, and integrates with the composite tissue repair patch, and has no shrinkage phenomenon. In the control group, the woven mesh, the new tissue and the blood vessels were few, and the new tissue did not grow into the woven mesh, and there was a serious shrinkage.
  • the composite tissue repair patch of Examples 2 and 4 did not have any adhesion to the tissue-organ contact surface.
  • the control woven mesh and the tissues and organs showed multiple adhesions.
  • the composite tissue repair patch of the present disclosure not only has the function of promoting tissue repair and regeneration, but also effectively prevents the material from shrinking and prevents the adhesion of organs, and is an ideal composite tissue repair patch.

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Abstract

L'invention concerne une feuille de réparation de tissu composite et un procédé de préparation et une application s'y rapportant. La feuille de réparation de tissu composite comprend : une membrane de nanofibres, un maillage tissé et un adhésif. L'adhésif est situé entre la membrane de nanofibres et le maillage tissé. L'adhésif comprend un matériau hydrophile. La membrane de nanofibres et le maillage tissé sont reliés par l'intermédiaire de l'adhésif, et l'adhésif entre dans les pores de la membrane de nanofibres et du maillage tissé. La résistance au pelage entre la membrane de nanofibres et le maillage tissé est de 20 à 75 cN/mm. La résistance à la rupture de la feuille de réparation de tissu composite est de 8 à 12,5 MPa. L'allongement à la rupture de la feuille de réparation de tissu composite est de 20 à 250 %. La porosité est de 50 à 90 %. La feuille de réparation de tissu composite n'est pas facilement délaminée et présente des propriétés mécaniques et une souplesse satisfaisantes.
PCT/CN2017/119133 2016-12-28 2017-12-27 Feuille de réparation de tissu composite et procédé de préparation et application s'y rapportant WO2018121630A1 (fr)

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CN112899324B (zh) * 2021-01-29 2022-07-01 北京诺康达医药科技股份有限公司 一种细菌纤维素膜及其乳房补片和制备方法
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