CN114681671A - Tissue repair membrane - Google Patents
Tissue repair membrane Download PDFInfo
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- CN114681671A CN114681671A CN202011608751.3A CN202011608751A CN114681671A CN 114681671 A CN114681671 A CN 114681671A CN 202011608751 A CN202011608751 A CN 202011608751A CN 114681671 A CN114681671 A CN 114681671A
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- layer
- film
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- repair
- membrane
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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
-
- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
- D06M10/00—Physical treatment of fibres, threads, yarns, fabrics, or fibrous goods made from such materials, e.g. ultrasonic, corona discharge, irradiation, electric currents, or magnetic fields; Physical treatment combined with treatment with chemical compounds or elements
- D06M10/005—Laser beam treatment
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- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
- D06M2101/00—Chemical constitution of the fibres, threads, yarns, fabrics or fibrous goods made from such materials, to be treated
- D06M2101/02—Natural fibres, other than mineral fibres
- D06M2101/10—Animal fibres
- D06M2101/14—Collagen fibres
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- D—TEXTILES; PAPER
- D06—TREATMENT OF TEXTILES OR THE LIKE; LAUNDERING; FLEXIBLE MATERIALS NOT OTHERWISE PROVIDED FOR
- D06M—TREATMENT, NOT PROVIDED FOR ELSEWHERE IN CLASS D06, OF FIBRES, THREADS, YARNS, FABRICS, FEATHERS OR FIBROUS GOODS MADE FROM SUCH MATERIALS
- D06M2101/00—Chemical constitution of the fibres, threads, yarns, fabrics or fibrous goods made from such materials, to be treated
- D06M2101/16—Synthetic fibres, other than mineral fibres
- D06M2101/30—Synthetic polymers consisting of macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- D06M2101/32—Polyesters
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Abstract
The invention relates to a tissue repairing film, which is a fiber film, wherein the fiber film comprises a substrate layer and a modification layer, and at least part of area in the modification layer is irradiated by energy rays to generate cladding, crosslinking and/or shrinkage; the fibrous membrane includes fibers derived from a composition comprising a naturally hydrophilic material. The invention can relieve or inhibit the problem that the size or the shape of the tissue repair membrane is changed due to swelling when in use by carrying out isomerization treatment on at least one modified layer of the tissue repair membrane, does not need to introduce other components, and can maintain the fiber structure in the tissue repair membrane.
Description
Technical Field
The invention belongs to the field of medical materials, particularly relates to a biomedical repairing material, and more particularly relates to a fibrous membrane for repairing human tissues and a medical repairing product comprising the fibrous membrane.
Background
Various clinical repair products have been tried in surgical practice for tissue defects caused by trauma, accidents, cancer, etc. In general, as a product that can perform tissue repair, not only good biocompatibility, appropriate degradability, and a certain strength are required, but also a component that facilitates cell adhesion or growth can be added to a medical product for tissue repair in order to promote tissue regrowth after a wound or accelerate wound healing.
Typically such tissue repair products may be provided in the form of a scaffold or repair membrane. Among them, the repair film may be formed of nanofibers in general through a spinning process, particularly, an electrospinning process. And the electrostatic spinning process has good application effect in the field of tissue repair by virtue of the advantages of nanoscale, high specific surface area, simulation of extracellular matrix and the like.
Further, due to the particularity of the structure and function of human tissue, the ideal fibrous membrane for tissue repair needs to have the following properties: the biocompatibility is good, the tissue growth can be guided, and the ideal repair is achieved; the cell is convenient to adhere, crawl and grow, and the tissue regeneration is realized; the material has certain strength, can resist mechanical stress, and can provide enough mechanical support before healthy tissues are not completely formed, such as the application to repair tissues such as peritoneum, ligaments and tendons; the texture is soft, the discomfort of the patient is reduced, and the operation effect is improved; the utility model has strong clinical practicability, is convenient for cutting, does not fall apart, and is easy to suture with tissues or attach with anatomical structures of the tissues; after being implanted into a human body, the implant can keep good dimensional stability and does not shrink or deform; preventing bacteria from hiding and breeding and avoiding infection caused by using artificial biosynthesis materials; more preferably, the tissue repair patch is degraded and absorbed in vivo after repair is complete.
Citation 1 discloses a chitosan-based nerve fiber membrane and a preparation method thereof. The chitosan-based nerve fiber membrane is formed by a plurality of composite nano fibers which are arranged in an oriented manner; each composite nanofiber is of a core-shell structure, the shell layer of each composite nanofiber comprises degradable functional materials, hydrophilic functional group modified carbon nanotubes, lycium barbarum polysaccharides and chitosan and/or chitosan derivatives, and the core layer of each composite nanofiber comprises nerve growth factors and a stabilizing agent.
Citation 2 discloses a functionalized guided muscle tissue repair membrane, and a preparation method and application thereof. The repairing film takes polycaprolactone and collagen as base materials, is a randomly arranged micron-sized fibrous film which is prepared through electrostatic spinning and has the fiber diameter of 1-10 mu m and the film thickness of 50-500 mu m, and also can comprise hydrogel of protein which is loaded on the repairing film and has a blood coagulation function and protein which is combined on the hydrogel and promotes cell growth.
Cited document 3 discloses a fiber membrane for tissue repair formed by interlacing fiber filaments having a diameter of 10nm to 100 μm and formed by electrospinning, the fiber filaments being made of one or more selected from the following polymer materials or derivatives thereof: collagen, cellulose, chondroitin sulfate, chitosan, modified chitosan, fibrin, silk protein, elastin mimetic peptide polymers, heparin, agar, dextran, alginic acid, modified cellulose, alginic acid, starch, polyols, block polyethers, gelatin, polyvinylpyrrolidone, polycaprolactone, polyglycolic acid, polylactic acid-glycolic acid copolymer, 1, 3-propylene glycol polymer, polylactic acid-caprolactone copolymer or polylactic acid, and the like.
Further, in the field of applying the conventional electrospun membrane material to tissue repair, as mentioned above, in order to improve the biocompatibility and tissue repair performance of the membrane material, natural hydrophilic materials such as collagen, gelatin and polysaccharide and synthetic materials such as polylactic acid are usually added to perform composite electrospinning, so as to promote the adhesion growth of histiocytes and the membrane material. However, in the case that some tissue fluids or other fluids exist in a large amount and for a long time, hydrophilic materials such as collagen, gelatin, polysaccharides and the like in the electrospun membrane material swell, resulting in structural changes such as fiber slippage or membrane material deformation, and such changes usually result in displacement of the membrane material after implantation or loss of the original pore barrier effect.
In order to maintain the original structure of easily swellable hydrophilic materials such as collagen and gelatin and to improve the stability of the structure during use, the conventional method is to crosslink and fix the hydrophilic materials by using a crosslinking agent. However, after the introduction of the crosslinking agent, the difficulty of removing some of the crosslinking agent remaining in the porous film material is high, and there is a possibility that the risk of new substance remaining increases. If traditional fusion modes such as hot pressing and the like are adopted, the integral fiber pore structure of the electrostatic spinning membrane material is easy to damage, so that the whole membrane material becomes compact, the flexibility becomes poor and the fit with a human body is poor.
It can be seen that there is still room in the art for further improvement in providing a medical product for repair that is more user friendly.
The cited documents are:
cited document 1: CN111632193A
Cited document 2: CN110404117A
Cited document 3: CN106492272B
Disclosure of Invention
Problems to be solved by the invention
In the case of a fibrous membrane for tissue repair which is generally used in the prior art, particularly, when the fibrous membrane is produced by an electrospinning method, an artificial synthetic material such as a natural hydrophilic material compounded with polylactic acid is generally used as a spinning material, and therefore, a film-like material obtained after electrospinning is likely to cause problems such as swelling and deformation in a solution, which affects the dimensional stability of the fibrous membrane.
Aiming at the problem, the invention provides a tissue repair membrane based on a fiber membrane, which is characterized in that at least part of the structure of the repair membrane is subjected to isomerization treatment, so that the fibers in the part of the structure of the repair membrane are subjected to isomerization modification, the fibers at other parts are kept unchanged, and the isomerization modified fibers can maintain the electrostatic spinning membrane, particularly the membrane obtained by electrostatic spinning, and do not swell and deform in a liquid environment.
In addition, the repairing film provided by the invention does not increase the risk of new substance residue, and can maintain the fiber structure in the film material unchanged.
Means for solving the problems
After long-term research, the inventor of the present invention finds that the technical problems can be solved by implementing the following technical scheme:
the invention firstly provides a tissue repairing film, wherein the repairing film is a fiber film,
the fiber film comprises a substrate layer and at least one modified layer, wherein at least partial region in the modified layer is subjected to energy ray irradiation to generate cladding, crosslinking or shrinkage;
the fibrous membrane includes fibers derived from a composition comprising a naturally hydrophilic material.
Wherein the modified layer is present in at least one major surface of the fibrous membrane or the modified layer forms at least one major surface of the fibrous membrane.
Further, the average thickness of each of the modified layers is 10% or less based on 100% of the average thickness of the fiber membrane.
Further, the area of the modification layer irradiated by the energy line forms one of grid-shaped, stripe-shaped, staggered-shaped or array point-shaped patterns or a combination pattern of the grid-shaped, stripe-shaped, staggered-shaped or array point-shaped patterns.
Further, the energy line comprises a flux of energetic particles or a flux of photon beams.
Preferably, the energy line is laser, and the ratio of the laser power W to the laser scanning speed V is 0.15-0.25.
Further, the average thickness of the fiber membrane is 0.5mm or less, preferably 0.1mm to 0.3 mm.
Further, the average porosity of the fiber membrane is 85% or less, preferably 40% to 80%.
Further, the composition containing the natural hydrophilic material also comprises an artificial synthetic material.
Preferably, the natural hydrophilic material in the composition containing the natural hydrophilic material is selected from one or more than two of gelatin, collagen and polysaccharide, and the artificial synthetic material comprises one or more than two of polyester materials; preferably, the mass ratio between the artificial synthetic material and the natural hydrophilic material is (20%: 80%) to (80%: 20%)
Further, the invention also provides a laminated body for tissue repair, wherein at least one layer in the laminated body comprises the tissue repair film.
ADVANTAGEOUS EFFECTS OF INVENTION
Through the implementation of the technical scheme of the invention, the following technical effects can be obtained:
1) through isomerization treatment on at least one modified layer of the tissue repair membrane, the problem that the size or the shape of the tissue repair membrane is changed due to swelling when the tissue repair membrane is used, so that the fit or fixation with human tissues is influenced, and the usability is reduced is solved;
2) the isomerization treatment of the modified layer of the tissue repair film provided by the invention can not only inhibit the problem of size change in use, but also provide improved mechanical properties for the repair film or is beneficial to increasing the self-supporting property of the repair film in a preferable case, and simultaneously provide better convenience in cutting the repair film;
3) through the isomerization treatment of the modified layer of the tissue repair membrane, the effect is realized without introducing other components, and the substance residue risk caused by the introduction of new substances is avoided.
4) The tissue repair membrane provided by the invention has the advantages of easiness in processing and low cost, and is beneficial to industrial large-scale application.
Drawings
FIG. 1: dry microscope transmission images of samples before and after laser surface treatment in one embodiment of the invention;
FIG. 2: a transmission image of a sample wet microscope after laser surface treatment in one embodiment of the invention;
FIG. 3: a wet microscope reflectance map of a sample before and after laser surface treatment in one embodiment of the invention;
FIG. 4: a wet microscope reflectance of a sample after laser surface treatment in one embodiment of the invention;
FIG. 5: SEM image (400 times) of a sample after laser surface treatment in one embodiment of the invention;
FIG. 6: SEM image (1000 times) of a laser surface treatment sample in one embodiment of the invention; FIG. 7: comparing the hydrophilicity of the surface of the repairing film before and after the laser surface treatment in a specific embodiment of the invention;
FIG. 8: photos of the sample animal at the time of experimental implantation before and after the laser surface treatment in one embodiment of the invention;
FIG. 9: the picture of the sample animal after the experiment implantation for 14 days after the laser surface treatment in one embodiment of the invention;
FIG. 10: in one embodiment of the invention, the photographs of the sample animals are taken 4 days after experimental implantation before laser surface treatment.
FIG. 11: a structural view of the repair film in one embodiment of the present invention (A: modified layer, B: base layer)
FIG. 12: a schematic illustration of the 7 day postoperative line removal observation in one embodiment of the invention.
Detailed Description
The following describes embodiments of the present invention, but the present invention is not limited to these embodiments. The present invention is not limited to the configurations described below, and various modifications are possible within the scope of the claims, and embodiments and examples obtained by appropriately combining the technical means disclosed in the respective embodiments and examples are also included in the technical scope of the present invention. All documents described in this specification are incorporated herein by reference.
Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
In the present specification, a numerical range represented by "a value to B value" or "a value to B value" means a range including the end point value A, B.
In the present specification, the meaning of "may" includes both the meaning of performing a certain process and the meaning of not performing a certain process. In this specification, "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event occurs and instances where it does not.
In the present specification, "%" represents mass or weight percent, i.e., "mass%" or "weight%" unless otherwise specified.
In the present specification, the "average thickness" is obtained by taking the unit area (for example, 1 cm)2) And measuring any 10 points in the unit area of the film, wherein the average value of the thicknesses of the 10 points is the average thickness.
In the present specification, the use of "substantially" or "substantially" means that the industrial error or the experimental error range is considered.
Reference throughout this specification to "some particular/preferred embodiments," "other particular/preferred embodiments," "some particular/preferred aspects," "other particular/preferred aspects," or the like, means that a particular element (e.g., feature, structure, property, and/or characteristic) described in connection with the embodiment is included in at least one embodiment described herein, and may or may not be present in other embodiments. In addition, it is to be understood that the described elements may be combined in any suitable manner in the various embodiments.
The terms "comprises" and "comprising," and any variations thereof, in the description and claims of this invention and the above-described drawings are intended to cover non-exclusive inclusions. For example, a process, method, or system, article, or apparatus that comprises a list of steps or elements is not limited to only those steps or elements but may alternatively include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.
< first aspect >
In a first aspect of the invention, a prosthetic film for human tissue repair is provided.
The repair film is a fiber film, the fiber film comprises a substrate layer and at least one modification layer, wherein at least partial region in the modification layer is subjected to energy ray irradiation to generate cladding, crosslinking and/or shrinkage; the fibrous membrane includes fibers derived from a composition comprising a naturally hydrophilic material.
Human tissue
The human tissue to which the present invention is directed is typically tissue that has been damaged, missing or otherwise injured as a result of an external accidental trauma or surgery. For such tissues, repair, treatment or healing can be obtained by using the repair film of the present invention.
Such tissues include, but are not limited to, the following: skin tissue, bone tissue, cartilage tissue, adipose tissue, dense connective tissue, loose connective tissue, muscle tissue, nerve tissue, and the like. Therefore, the repairing film provided by the invention can be used on the surface of the skin of a human body and can also be used in the human body.
Fiber raw material
The repair film of the present invention is a fiber film formed of fibers. For the raw material forming the fiber, it should generally have good biocompatibility and degradability, and at the same time, the material should be soft but have a certain strength to satisfy the conformability to human tissue, supportability, and the like.
Thus, in some embodiments of the invention, such fiber materials may include naturally hydrophilic materials, and, in addition, preferably, synthetic materials having degradability, biocompatibility, and the like.
For the natural hydrophilic material, in some specific embodiments of the present invention, a substance selected from hydrophilic colloids, proteins or polysaccharides, etc. may be selected. In some preferred embodiments, the collagen may be selected from one or more of gelatin, proto-protein, human recombinant collagen, cellulose, chondroitin sulfate, chitosan, modified chitosan, fibrin, silk protein, elastin mimetic peptide polymers, heparin, agar, dextran, alginic acid, modified cellulose, alginic acid, starch, and the like, and modifications (e.g., cross-linking, etc.) thereof.
The degradable biocompatible synthetic material is not particularly limited, and may be selected from synthetic materials that are conventional in the art. In some specific embodiments of the present invention, for such materials, for example, one or more selected from polylactic acid, polycaprolactone, polyhydroxybutyrate-valerate, polydioxanone, polyvinylpyrrolidone, polycaprolactone, polyglycolic acid, polylactic-glycolic acid copolymer, 1, 3-propanediol polymer, polylactic-caprolactone copolymer, polyvinyl alcohol, and the like may be used. Preferably, the synthetic material includes a polyester material.
In addition, the fiber material may contain other auxiliary components in addition to the natural hydrophilic material and the synthetic material, without affecting the technical effect of the present invention. Such ingredients are not particularly limited and may be selected from:
i) inorganic components such as nano metal oxide particles, hydroxyapatite and a modified product thereof, graphene oxide, and the like;
ii) bioactive components, for example, bioactive modified inorganic components of biological growth factors (including epidermal growth factor, fibroblast growth factor, and the like, capable of promoting rapid wound healing, adhesion prevention, and the like);
iii) pharmaceutical ingredients, e.g., various antibiotics;
iv) auxiliary components, such as dispersants, initiators, crosslinking agents, etc.
In the present invention, the fiber for a fiber membrane can be produced by forming a raw material composition by arbitrarily mixing the above fiber raw materials. In some embodiments of the invention, such fibers may have substantially the same composition, or, alternatively, fibers processed from fiber materials of the same composition; in other embodiments of the invention, such fibers may have different compositions, or the fibers forming the fibrous membrane may be a blend of fibers from fiber sources having different compositions.
Further, the composition of the fiber raw material or the raw material composition of the present invention can be adjusted according to various actual needs. In a preferred embodiment of the present invention, the mass ratio of the synthetic material to the natural hydrophilic material in the fibrous membrane is 20% to 80% to 20%, preferably 30% to 70% to 30%, more preferably 35% to 65% to 35%, based on 100% of the total mass of the synthetic material and the natural hydrophilic material in the fibrous membrane.
Fiber membrane
The fiber membrane of the present invention is formed from the fibers obtained from the fiber material.
The method of forming the fiber film is not particularly limited, and may be performed by a method such as non-woven or woven.
In some preferred embodiments of the present invention, the fiber membrane of the present invention is obtained using an electrospinning method from the viewpoint of controllability as well as processability.
The principle of electrospinning is that a high voltage is applied to a polymer liquid during electrospinning to induce charge into the liquid. When charges in the liquid are accumulated to a certain amount, the liquid can form a Taylor cone at the spray head, liquid jet flow is formed by overcoming surface tension under the action of an external electric field force, and then the polymer jet flow moves along an irregular spiral track under the combined action of electrostatic repulsion, Coulomb force (Coulomb) and surface tension. The jet is drawn and stretched in a very short time, and as the solvent evaporates or heat is dissipated, the polymer jet solidifies to form the micro/nano fibers. In the electrostatic spinning process, a plurality of parameters can influence the final electrostatic spinning fiber, and the micron/nano fiber with different sizes, forms and structures can be prepared and obtained by controlling the process parameters.
In some specific embodiments of the present invention, the electrospinning method mainly includes the following steps of electrospinning to form a film, removing the solvent, and performing other subsequent processing steps:
(electrospinning film formation)
In the step of electrostatic spinning film formation, a fiber film is obtained mainly by mixing a fiber raw material with a solvent and by means of electrostatic spinning.
Specifically, a fiber raw material is prepared in advance, and the fiber raw material is dissolved in an appropriate solvent to prepare a spinning dope of the fiber raw material at a constant concentration.
The specific concentration of the solvent species forming the solution is not particularly limited as long as the requirements of the subsequent electrospinning process can be met. For example, a suitable solvent may be one or a combination of two or more of trifluoroethanol, hexafluoroisopropanol, trifluoroacetic acid, cyclohexanone, acetone, butanone, tetrahydrofuran, chloroform, glacial acetic acid, formic acid, propionic acid, or water, and in some preferred embodiments of the present invention, a solvent containing a fluorine atom is used from the viewpoint of solubility and solution viscosity.
In some specific embodiments of the present invention, the total mass volume percent concentration of the artificial material and the natural hydrophilic material in the electrospinning solution containing the fiber raw material is in the range of 5g/100mL to 10g/100mL, preferably in the range of 6g/100mL to 9g/100 mL.
The fiber raw material may be prepared as a raw material having the same composition, or two or more raw materials having different compositions may be prepared and each of them may be formed into a raw material liquid.
Further, there is no particular requirement for the electrospinning equipment used in the electrospinning film formation, and single spinning or co-spinning equipment commonly used in the art may be used. The required (nano-scale) fiber materials can be prepared by adjusting spinning parameters in these devices during the electrospinning film-forming process. Such as voltage, extrusion flow and electric field acceptance distance, spinning environment, etc. In some specific embodiments, the electrospinning process parameters of the present invention may be:
the feed liquid is propelled at a speed of 3-8 mL/h, preferably 3.5-7 mL/h;
the spinning voltage is 10-40 kV, preferably 20-40 kV, more preferably 22-38 kV, and more preferably 26-36 kV;
the extrusion flow rate of the solution is 0.1-15 mL/h, preferably 0.3-10 mL/h;
the receiving distance of the electric field is 5-30 cm, preferably 10-25 cm;
the environmental conditions for electrospinning are not particularly limited, and may be adjusted as needed, and for example, the relative temperature of the spinning environment may be controlled to 60% or less, and the environmental temperature may be controlled to 10 to 40 ℃.
The spinning may be stopped when the thickness of the fiber membrane obtained by spinning satisfies the requirement, and for example, the electrospinning may be stopped at any time when the average thickness of the fiber membrane is not more than 0.5 mm.
(solvent removal)
After spinning was stopped, the solvent of the resulting fiber membrane was removed. In some specific embodiments of the present invention, the solvent may be removed by directly drying the electrospun fiber membrane by heating or freeze-drying, or by immersing the fiber membrane in an organic solvent and then drying the fiber membrane.
In some preferred embodiments of the present invention, the fiber membrane containing a solvent, which can be obtained by electrospinning, is immersed in a solution containing an alcohol substance (e.g., methanol or ethanol, etc.) having a medium or low boiling point (a boiling point of not more than 100 ℃, preferably not more than 90 ℃) to wash it, thereby dissolving the solvent contained in the fiber membrane.
In such a solution, the content of the alcohol is preferably 70% by mass or more, more preferably 80% by mass or more, and still more preferably 90% by mass or more, based on the total mass of the solution. The washing is followed by drying to further remove these alcohol-containing solutions. Such drying may be carried out under heating and/or reduced pressure.
(other steps)
In the present invention, in addition to the above treatment in the electrospinning step, other treatment steps may be used as needed.
For example, the electrospun fiber membrane may be subjected to a crosslinking treatment before or after the solvent removal step as desired to at least partially crosslink the fiber membrane material to provide the necessary mechanical properties. In addition, the requirements of different wounds or clinical operations on the service cycle of the repair membrane can be met by regulating and controlling the crosslinking degree. It should be noted that such crosslinking should be controlled to a certain degree of crosslinking or less so as not to affect the degradability of the fiber film.
It should be noted that the crosslinking treatment or the use of the crosslinking agent in the present invention is not essential, and is merely means or components that can be selected without affecting the technical effect of the present invention.
In some embodiments of the present invention, after the fiber membrane is obtained through the electrospinning film-forming step, the obtained fiber membrane may be directly subjected to a heating and drying process. Such a method is suitable in the case where the fibre raw material already comprises or is added with a cross-linking agent and/or an initiator. In such cases, it is generally advantageous that the above-described solvent removal step can be carried out simultaneously with the crosslinking treatment. This is to take into account that the impregnation by the alcohol during the solvent removal step may lead to spillage of the cross-linking agent and/or initiator.
In other embodiments of the invention, additional means may be employed to accomplish the crosslinking treatment simultaneously with the solvent removal step. In this case, the fiber membrane obtained by electrospinning to form a membrane can be immersed in the solution containing the alcohol substance (for example, methanol or ethanol) having a medium or low boiling point (boiling point of not more than 100 ℃ C., preferably not more than 90 ℃ C.). Such a solution also contains a crosslinking agent capable of causing crosslinking of the fiber membrane. Such a crosslinking agent may include one or a combination of two or more of carbodiimide, N-hydroxysuccinimide, genipin, and aldehyde compounds. Further, the crosslinking condition can be controlled by adjusting the reaction conditions of the crosslinking treatment and the amount of the crosslinking agent. For example, the crosslinking treatment temperature, the crosslinking treatment time, the mass ratio of the crosslinking agent to the fiber membrane, the mass ratio of the crosslinking agent to the solution, and the like. The reaction conditions in the crosslinking step in the present invention may be such that the crosslinking treatment temperature is 1 to 50 ℃, preferably 4 to 30 ℃. The crosslinking treatment time is between 1 and 72 hours, preferably between 6 and 24 hours. The mass ratio of the chemical crosslinking agent to the fiber raw material (or the dry weight of the fiber membrane) in the fiber membrane is 0.1-3: 1, preferably 0.5-2: 1.
In the present invention, a (dried) fiber membrane is obtained by the above-mentioned method, wherein the average diameter of the fibers in the fiber membrane is 0.5 to 1.0 μm, preferably 0.6 to 1.0 μm.
Modification of fibrous membranes
Further, the fiber membrane is subjected to isomerization modification of at least a part of its structure to obtain a modified layer and a base layer (hereinafter, for convenience of description, the modified layer is sometimes represented by a layer a, and the base layer is sometimes represented by a layer B). In the present invention, the matrix layer is a portion or layer of the fiber membrane that is not subjected to isomerization modification.
In the present invention, with respect to the isomerization treatment, in some specific embodiments, by the isomerization treatment, at least one of the following conditions i to iv can be made to exist for the fiber membrane modification layer and the base layer:
i) the apparent density of the modified layer is higher than that of the base layer;
ii) the degree of crosslinking of the modification layer is higher than the degree of crosslinking of the matrix layer;
iii) the mechanical strength of the modification layer is different from (i.e., higher or lower than) the mechanical strength of the base layer;
iv) the porosity of the modification layer is lower than the porosity of the matrix layer.
The isomerization treatment according to the present invention may be performed by irradiation with an energy ray. The energy line may include high energy rays, ultraviolet light, or laser light. The modification layer may be irradiated with such an energy beam to cause cladding, cross-linking and/or shrinkage of at least a portion of the irradiated region of the modification layer.
Further, in each modified layer, the area to be subjected to isomerization treatment or irradiation with energy rays is 20% or more, preferably 40% or more, more preferably 50% or more of the total area, based on the total area of the layer; the upper limit of the area to be subjected to the isomerization treatment or the energy ray irradiation is not particularly limited, but may be 80% or less, preferably 70% or less, and more preferably 60% or less, from the viewpoint of processability, workability, strength, and degradability.
In some specific embodiments of the present invention, the irradiating may be irradiating at least one major surface of the fibrous membrane such that at least a portion of the major surface area of the fibrous membrane is isomerically modified. The modified fiber film thus obtained had a layer A/layer B structure. Alternatively, the fiber membrane may be irradiated with both main surfaces thereof, and the modified fiber membrane thus obtained may have a structure of a layer a/B/a.
In other specific embodiments of the present invention, the A layer/(B layer/A layer) can also be formed in the fiber film by irradiation with energy raysxlayer/B/(layer A)yAnd (5) structure. Wherein x is an integer greater than 1, preferably 1 to 5, and more preferably 1 to 3; y is 0 or 1.
Typically, a structure of a layer/B layer/a layer/B layer or a layer/B layer/a layer may be formed. Such a method of embedding the modified layer a in the middle of the layer B as the base layer can be obtained by processing with an auxiliary energy ray irradiation device in the above-described step of electrospinning film formation.
Specifically, after the electrospinning is carried out to a certain set thickness, the energy beam irradiation device is used to irradiate the surface of the fiber, and the irradiated portion is modified by isomerization, and then the electrospinning is continued. In such a process, the irradiation of the energy ray is controlled to be as short as possible to avoid an influence on the electrospinning process. Further, after the electrostatic spinning film forming and the subsequent treatment are finished to obtain the fiber film, at least one surface of the fiber film is irradiated by energy to isomerize and modify at least partial area of the surface of the fiber film.
In the present invention, when one isomerization-modified fiber membrane has a plurality of modification layers a, the properties of the modification layers (at least one of the apparent density, the degree of crosslinking, and the mechanical strength of the modification layers) may be the same or different.
In some preferred embodiments of the present invention, when the modified fibrous membrane has a structure of a layer/B layer/a layer, both a layers have the same properties.
In other preferred embodiments of the present invention, the modified fibrous membrane has a layer A/(layer B/layer A)xlayer/B/(layer A)yWhen in structure, the A layer on the surface layer of the fiber membrane has different properties from the A layer in the interior of the fiber membrane. More preferably, the a layer at the surface layer of the fiber membrane has a higher apparent density or degree of crosslinking than the a layer at the inside of the fiber membrane.
Further, a pattern may be formed on the irradiated surface of the fiber film by irradiation of the energy ray, and such a pattern is not particularly limited, and may include one of a grid pattern, a stripe pattern, a staggered pattern, or an array of dots, or a combination pattern thereof. In some preferred embodiments of the present invention, the pattern comprises lines staggered horizontally and vertically, and the distance between two adjacent parallel lines is 0.2mm to 1.0 mm. Other auxiliary methods for forming a pattern are not particularly limited, and a mask or a lens may be used as necessary.
In the present invention, the energy line is preferably a laser in view of convenience of operation and reliability of processing. When laser light is used for illumination, there may be one or more laser light sources. The desired pattern is formed by scanning of the laser light source, or the pattern may be formed by direct irradiation of an array or combination of a plurality of light sources.
The laser device applicable to the present invention is not particularly limited. In addition, the ratio of the laser power W to the laser scanning speed V can be controlled within the range of 0.15-0.25, preferably within the range of 0.18-0.23, so as to be beneficial to endowing the modified layer with more reliable performance. If the ratio is too low, the degree of modification of the surface to be processed may be insufficient, and if the ratio is too high, the surface to be processed may be damaged.
Further, as for the thicknesses of the modified layer and the base layer, in some specific embodiments of the present invention, the average thickness of each modified layer is 10% or less, preferably 8% or less, more preferably 5% or less, and still more preferably 3% or less, based on 100% of the average thickness of the fiber film containing the modified layer. The lower limit of the average thickness of each modified layer may be 0.5% or more, preferably 1% or more.
The average pore diameter of the final fiber membrane with the modified layer obtained according to the invention is 0.5-1.5 μm, preferably 0.6-1.2 μm; the average porosity is less than 85%, preferably 40-80%; the average thickness is 0.5mm or less, preferably 0.4mm or less, and more preferably 0.35mm or less, and the lower limit of the average thickness is not particularly limited, but may be 0.05mm or more, preferably 0.1mm or more, from the viewpoint of repairability and usability when used as a repair film.
< second aspect >
In a second aspect of the invention, a medical product for human tissue repair is provided.
In the present invention, the fiber film having the modified layer disclosed in the first aspect above can be used as it is as a repair film. In addition, other active ingredients, medicinal ingredients, and the like may be compounded or supported in the repair film as needed, and these other ingredients are not particularly limited and may be used as needed.
In some embodiments of the present invention, the repair film of the present invention may be combined with a layer having a supporting function to obtain a laminate. Typically, a woven mesh may be used as a support layer. In such a case, the present invention may further provide a laminate comprising a fibrous film having a modifying layer, a woven mesh, and an adhesive layer, wherein the adhesive layer is between the nanofiber film and the woven mesh. The adhesion material comprises a hydrophilic substance, the fiber film and the woven mesh are combined through the adhesion layer, and the adhesion layer is at least partially embedded into pores of the fiber film and the woven mesh. The hydrophilic substance includes: protein compounds and derivatives thereof modified by one or more of carbodiimide, carbodiimide/N-hydroxysuccinimide, genipin and aldehyde compounds, cellulose compounds and derivatives thereof modified by the aldehyde compounds, and one or more of chitosan compounds and derivatives thereof modified by glycerol and water; the peel strength between the fiber film and the woven mesh is 20-75 cN/mm; the fracture strength of the composite tissue repair patch is 8-12.5 Mpa; the distance between the nanofiber membrane and the woven mesh is 0.1-3 mm.
In some other embodiments of the present invention, the repair film of the present invention may be further compounded with a peelable layer to obtain a laminate. The material of the peelable layer is not particularly limited, and a conventional thermoplastic resin, particularly a polyolefin resin, a polyester resin, or the like, which is used in the present invention, can be used. The strippable layer can be electrostatically bonded to the repair film of the invention; further, the side of the peelable layer to which the repair film of the present invention is bonded may be coated with an adhesive.
Examples
The present invention will be further described below by way of specific examples.
Example 1
(1) Gelatin and PLLA are mixed according to a mass ratio of 1: 3 in a certain volume of hexafluoroisopropanol solvent, so that the total mass volume percentage concentration of the gelatin and the PLLA is 8g/100 mL;
(2) loading the polymer solution into an electrostatic spinning injector, adjusting the speed of a micro injection pump to be 5ml/h, adjusting the voltage difference of a high-voltage generator to be 30KV, adjusting the receiving distance of a receiving device to be 20 cm, preparing a fiber membrane crossed by mistake through electrostatic spinning, closing the electrostatic spinning when the thickness of the fiber membrane reaches 0.15mm, and taking down the fiber membrane;
(3) repeatedly soaking the electrospun fiber membrane material in 95% ethanol solution for many times to remove hexafluoroisopropanol, and then drying. A sample was prepared as shown in fig. 7 before laser surface treatment.
(4) And (3) placing the dried membrane on a Laser Tools & technologies corporation (ILS IIINM-25W) platform for Laser surface treatment. Setting the laser power to be 22 percent and the laser speed to be 100 percent, namely setting the ratio of the laser power to the laser scanning speed to be 0.22, and setting the scanning CAD graph to be a horizontal and vertical staggered running track with the interval of 0.5 mm. And carrying out laser surface treatment on the surface of the membrane material to obtain a sample after the laser surface treatment in the figure 7. The microscope pictures of the sample are shown in fig. 1 to 4, and the electron microscope SEM pictures are shown in fig. 5 to 6. The samples after the test laser surface treatment had an average pore diameter of 0.86 μm, an average fiber diameter of 0.74 μm and an average porosity of 66.30%.
The surface hydrophilicity and hydrophobicity of the surface-treated membrane material are obviously changed, as shown in fig. 7. Can obviously slow down the swelling effect of the liquid.
(5) The samples before and after laser surface treatment are irradiated and sterilized for repairing the lower jaw defect animal model after tooth extraction.
Namely, beagle dogs are fasted 12 hours before operation and anesthetized by intravenous injection with 3% concentration sodium pentobarbital according to 1 ml/kg. After anesthesia, hair around the mandibular operation portion was removed. The skin inside and around the mouth was disinfected with iodophor and draped. Separating gingival flaps around 1 st, 2 nd, 3 rd and 4 th premolars, ensuring periosteum to be complete, and removing 1 st, 2 nd, 3 rd and 4 th premolars on two sides of the lower jaw. And then the gingival flap is sutured again, the animal is placed back to a feeding room for observation and feeding after reviving, and the animal is injected with antibiotics for 3 days after operation to prevent infection.
To prevent gingival fissure at the suture, animals were fed liquid diet for the first 15 days after surgery and evaluated for healing weekly until complete healing. And 3 months after tooth extraction, making a lower jaw defect animal model. The specific operation is as follows: incising from the lateral surface of the lower jaw, and separating the buccal gingiva at the tooth extraction position to the alveolar ridge by using a gingival separator to ensure the integrity of the periosteum. 2 three-wall box-shaped defects (cooled by a large amount of physiological saline solution while edging) are respectively manufactured at the left and right tooth extraction positions by a dental drill, the two defects are separated by 5mm, the lower alveolar nerve and blood vessels are not damaged in the operation process, and the length, width and height of the defects are 9mm multiplied by 5mm multiplied by 7 mm. Placing bone powder uniformly mixed with autologous blood in the tooth extraction pit, properly extruding to make the height of the bone powder be flush with the defect surface, covering a laser surface treatment repairing film sample above the bone powder, and nailing bone nails at four corners for fixation. The gums are then sutured as shown in fig. 8. After 14 days of operation, the material was observed dissectively without swelling, falling off and shifting, soft tissue growth was observed on the membrane, and the gingiva was healed, as shown in fig. 9. On the other hand, the samples before laser treatment showed swelling, displacement and exposure of the membrane material on the 4 th day after implantation, as shown in fig. 10.
Example 2
(1) Gelatin and PLLA are mixed according to a mass ratio of 7: 3 in a certain volume of hexafluoroisopropanol solvent, so that the total mass volume percentage concentration of the gelatin and the PLLA is 8g/100 mL;
(2) loading the polymer solution into an electrostatic spinning injector, adjusting the speed of a micro injection pump to be 6 ml/h, adjusting the voltage difference of a high-voltage generator to be 30KV, adjusting the receiving distance of a receiving device to be 22 cm, preparing a fiber membrane crossed by mistake through electrostatic spinning, closing the electrostatic spinning when the thickness of the fiber membrane reaches 0.2mm, and taking down the fiber membrane;
(3) repeatedly soaking the electrospun fiber membrane material in 95% ethanol solution for many times to remove hexafluoroisopropanol, and then drying. And preparing a sample before laser surface treatment.
(4) And (3) placing the dried membrane on a Laser Tools & technologies corporation (ILS IIINM-25W) platform for Laser surface treatment. Setting the laser power to be 18 percent and the laser speed to be 100 percent, namely setting the ratio of the laser power to the laser speed to be 0.18: and setting the scanning CAD graph as a horizontal and vertical staggered running track with the interval of 0.2 mm. And carrying out laser surface treatment on the surface of the membrane material to obtain a sample subjected to laser surface treatment. The average pore diameter of the test laser-surface-treated sample was 0.63. mu.m, the average fiber diameter was 0.61. mu.m, and the average porosity was 73.1%
(5) The samples before and after laser surface treatment are irradiated and sterilized for repairing the lower jaw defect animal model after tooth extraction.
Namely, beagle dogs are fasted 12 hours before operation and anesthetized by intravenous injection with 3% concentration sodium pentobarbital according to 1 ml/kg. After anesthesia, hair around the mandibular surgery portion was removed. The skin inside and around the mouth was disinfected with iodophor and draped. Separating gingival flaps around the 1 st, 2 nd, 3 rd and 4 th premolars, ensuring periosteum to be complete, and removing the 1 st, 2 nd, 3 rd and 4 th premolars on both sides of the lower jaw. And then the gingival flap is sutured again, the animal is placed back to a feeding room for observation and feeding after reviving, and the animal is injected with antibiotics for 3 days after operation to prevent infection.
To prevent gingival fissure at the suture, animals were fed liquid diet for the first 15 days after surgery and evaluated for healing weekly until complete healing. And 3 months after tooth extraction, making a lower jaw defect animal model. The specific operation is as follows: incise from the lateral surface of the lower jaw, and separate the buccal gingiva at the tooth extraction position to the alveolar ridge by using a gingival separator to ensure the integrity of periosteum. 2 three-wall box-shaped defects (cooled by a large amount of physiological saline solution while edging) are respectively manufactured at the left and right tooth extraction positions by a dental drill, the two defects are separated by 5mm, the lower alveolar nerve and blood vessels are not damaged in the operation process, and the length, width and height of the defects are 9mm multiplied by 5mm multiplied by 7 mm. Placing bone powder uniformly mixed with autologous blood in the tooth extraction pit, properly extruding to make the height of the bone powder be flush with the defect surface, covering a laser surface treatment repairing film sample above the bone powder, and nailing bone nails at four corners for fixation. Then the gingiva was sutured, and 7 days after surgery, the stitches were removed to observe that the material was not exposed to drop and shift, and the gingiva was well healed, as shown in fig. 12.
Example 3
(1) Gelatin and PLLA are mixed according to a mass ratio of 2: 5 in a certain volume of hexafluoroisopropanol solvent, so that the total mass volume percentage concentration of the gelatin and the PLLA is 8g/100 mL;
(2) loading the polymer solution into an electrostatic spinning injector, adjusting the speed of a micro injection pump to be 6 ml/h, adjusting the voltage difference of a high-voltage generator to be 30KV, adjusting the receiving distance of a receiving device to be 22 cm, preparing a fiber membrane crossed by mistake through electrostatic spinning, closing the electrostatic spinning when the thickness of the fiber membrane reaches 0.3mm, and taking down the fiber membrane;
(3) repeatedly soaking the electrospun fiber membrane material in 95% ethanol solution for many times to remove hexafluoroisopropanol, and then drying. And preparing a sample before laser surface treatment.
(4) And (3) placing the dried membrane on a Laser Tools & technologies corporation (ILS IIINM-25W) platform for Laser surface treatment. Setting the laser power to be 20% and the laser speed to be 100%, namely setting the ratio of the laser power to the laser speed to be 0.20: and setting the scanning CAD graph as a horizontal and vertical staggered running track with the interval of 0.3 mm. And carrying out laser surface treatment on the surface of the membrane material to obtain a sample subjected to laser surface treatment. The average pore diameter of the test laser-surface-treated sample was 0.75. mu.m, the average fiber diameter was 0.68 μm, and the average porosity was 75.3%
(5) The samples before and after laser surface treatment are irradiated and sterilized for repairing the lower jaw defect animal model after tooth extraction.
Namely, beagle dogs are fasted 12 hours before operation and anesthetized by intravenous injection with 3% concentration sodium pentobarbital according to 1 ml/kg. After anesthesia, hair around the mandibular surgery portion was removed. The skin inside and around the mouth was disinfected with iodophor and draped. Separating gingival flaps around 1 st, 2 nd, 3 rd and 4 th premolars, ensuring periosteum to be complete, and removing 1 st, 2 nd, 3 rd and 4 th premolars on two sides of the lower jaw. And then the gingival flap is sutured again, the animal is placed back to a feeding room for observation and feeding after reviving, and the animal is injected with antibiotics for 3 days after operation to prevent infection.
To prevent gingival dehiscence at the suture, animals were fed liquid diet for the first 15 days post-surgery, and weekly for evaluation of healing until complete healing. And 3 months after tooth extraction, making a lower jaw defect animal model. The specific operation is as follows: incise from the lateral surface of the lower jaw, and separate the buccal gingiva at the tooth extraction position to the alveolar ridge by using a gingival separator to ensure the integrity of periosteum. 2 three-wall box-shaped defects (cooled by a large amount of physiological saline solution while edging) are respectively manufactured at the left and right tooth extraction positions by a dental drill, the two defects are separated by 5mm, the lower alveolar nerve and blood vessels are not damaged in the operation process, and the length, width and height of the defects are 9mm multiplied by 5mm multiplied by 7 mm. Placing bone powder uniformly mixed with autologous blood in the tooth extraction pit, properly extruding to enable the height of the bone powder to be flush with the defect surface, covering a laser surface treatment repairing film sample above the bone powder, and nailing bone nails at four corners for fixing. Then the gingiva is sutured, and 14 days after the operation, the stitches are removed to observe that the materials are not exposed, shed and displaced, and the gingiva is well healed.
It should be noted that, although the technical solutions of the present invention are described by specific examples, those skilled in the art can understand that the present disclosure should not be limited thereto.
Having described embodiments of the present disclosure, the foregoing description is intended to be exemplary, not exhaustive, and not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen in order to best explain the principles of the embodiments, the practical application, or improvements made to the technology in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.
Industrial applicability
The tissue repair membrane based on the fiber membrane provided by the invention can be industrially prepared and used as a product for medical repair.
Claims (11)
1. A tissue repair film, which is characterized in that the repair film is a fiber film,
the fiber film comprises a substrate layer and at least one modified layer, wherein at least partial area in the modified layer is subjected to energy ray irradiation to generate cladding, crosslinking and/or shrinkage;
the fibrous membrane includes fibers derived from a composition comprising a naturally hydrophilic material.
2. Repair film according to claim 1, characterized in that the modification layer is present at least in one main surface of the fibre film or forms at least one main surface of the fibre film.
3. The repair film according to claim 1 or 2, wherein the average thickness of each modification layer is 10% or less based on 100% of the average thickness of the fiber film.
4. The repair film according to any one of claims 1 to 3, wherein a grid pattern, a stripe pattern, a staggered pattern, an array pattern, or a combination pattern thereof is formed in a region of the modified layer of the fiber film irradiated with the energy ray.
5. The repair film of any one of claims 1 to 4, wherein the energy beam comprises a stream of energetic particles or a stream of photonic beams.
6. The repair film according to any one of claims 1 to 5, wherein the energy line is a laser, and a ratio of the laser power W to the laser scanning speed V is 0.15 to 0.25.
7. The repair film according to any one of claims 1 to 6, wherein the average thickness of the fiber film is 0.5mm or less, preferably 0.1mm to 0.3 mm.
8. The repair film according to any one of claims 1 to 7, wherein the average porosity of the fiber film is 85% or less, preferably 40% to 80%.
9. The repair film according to any one of claims 1 to 8, wherein the composition containing the natural hydrophilic material further comprises a synthetic material.
10. The repair film according to claim 9, wherein the composition containing the natural hydrophilic material comprises one or more natural hydrophilic materials selected from gelatin, collagen, and polysaccharides, and the synthetic material comprises one or more polyester materials; preferably, the mass ratio of the artificially synthesized material to the natural hydrophilic material is (20%: 80%) to (80%: 20%).
11. A laminated body for tissue repair, wherein at least one layer of the laminated body comprises the tissue repair film according to any one of claims 1 to 10.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102166378A (en) * | 2011-01-13 | 2011-08-31 | 北京化工大学 | Tissue regeneration guiding membrane 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 |
WO2016107522A1 (en) * | 2014-12-29 | 2016-07-07 | 深圳迈普再生医学科技有限公司 | Soft tissue repair patch and preparation method thereof, and tension-free hanging belt system |
CN110404117A (en) * | 2018-04-28 | 2019-11-05 | 国家纳米科学中心 | A kind of functionalization guidance muscular tissue repair membrane and its preparation method and application |
-
2020
- 2020-12-30 CN CN202011608751.3A patent/CN114681671A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102166378A (en) * | 2011-01-13 | 2011-08-31 | 北京化工大学 | Tissue regeneration guiding membrane 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 |
WO2016107522A1 (en) * | 2014-12-29 | 2016-07-07 | 深圳迈普再生医学科技有限公司 | Soft tissue repair patch and preparation method thereof, and tension-free hanging belt system |
CN110404117A (en) * | 2018-04-28 | 2019-11-05 | 国家纳米科学中心 | A kind of functionalization guidance muscular tissue repair membrane and its preparation method and application |
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