CN112076022A - Wound dressing paste and preparation method thereof - Google Patents

Wound dressing paste and preparation method thereof Download PDF

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Publication number
CN112076022A
CN112076022A CN202011055525.7A CN202011055525A CN112076022A CN 112076022 A CN112076022 A CN 112076022A CN 202011055525 A CN202011055525 A CN 202011055525A CN 112076022 A CN112076022 A CN 112076022A
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film layer
polylactic acid
wound dressing
layer
organic solvent
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CN112076022B (en
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贺永
高庆
林海波
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Suzhou Yongqinquan Intelligent Equipment Co ltd
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Suzhou Yongqinquan Intelligent Equipment Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F13/00Bandages or dressings; Absorbent pads
    • A61F13/01Non-adhesive bandages or dressings
    • A61F13/01021Non-adhesive bandages or dressings characterised by the structure of the dressing
    • A61F13/01029Non-adhesive bandages or dressings characterised by the structure of the dressing made of multiple layers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F13/00Bandages or dressings; Absorbent pads
    • A61F13/00051Accessories for dressings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F13/00Bandages or dressings; Absorbent pads
    • A61F13/00051Accessories for dressings
    • A61F13/00063Accessories for dressings comprising medicaments or additives, e.g. odor control, PH control, debriding, antimicrobic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F13/00Bandages or dressings; Absorbent pads
    • A61F13/00987Apparatus or processes for manufacturing non-adhesive dressings or bandages
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F13/00Bandages or dressings; Absorbent pads
    • A61F13/01Non-adhesive bandages or dressings
    • A61F13/01008Non-adhesive bandages or dressings characterised by the material
    • A61F13/01012Non-adhesive bandages or dressings characterised by the material being made of natural material, e.g. cellulose-, protein-, collagen-based
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F13/00Bandages or dressings; Absorbent pads
    • A61F13/01Non-adhesive bandages or dressings
    • A61F13/01008Non-adhesive bandages or dressings characterised by the material
    • A61F13/01017Non-adhesive bandages or dressings characterised by the material synthetic, e.g. polymer based
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/26Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/28Polysaccharides or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/32Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/32Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
    • A61L15/325Collagen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/44Medicaments
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/62Compostable, hydrosoluble or hydrodegradable materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/04Materials for stopping bleeding

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Materials Engineering (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Manufacturing & Machinery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The invention discloses a wound dressing paste, which comprises: a support layer; a first film layer, a second film layer and a wound dressing layer which are sequentially fixed on the supporting layer; the first film layer can be automatically separated from the second film layer after the second film layer is degraded. The invention also discloses a preparation method of the wound dressing patch. According to the wound dressing paste, the first film layer and the second film layer with larger spatial structure difference are constructed on the surface of the supporting layer, so that the wound dressing paste can automatically fall off in the use process of the wound dressing paste. The non-woven fabric supporting layer, the first film layer, the second film layer and the wound dressing layer are all of a microporous structure, have good air permeability and moisture retention performance, can effectively prevent the wound from further deterioration caused by oxygen deficiency, softening and the like of skin around the wound, and are beneficial to rapid healing of the wound. The wound dressing paste prepared by the technology has the characteristics of good mechanical strength, air permeability, moisture retention, good biocompatibility, in-vitro degradability and automatic falling.

Description

Wound dressing paste and preparation method thereof
Technical Field
The invention relates to a wound dressing adhesive and a preparation method thereof, in particular to the structural construction and the functional design of the wound dressing adhesive, and belongs to the technical field of medical supplies.
Background
The skin is the first barrier of the organism against the invasion of external bacteria and viruses. Particularly for the human body, the skin can be regarded as the largest immune organ of the human body. The human skin comprises epidermis, dermis and subcutaneous tissues and has multiple functions of protecting the body, preventing invasion of microorganisms such as bacteria and viruses, regulating the temperature of the human body, preventing loss of body fluid of the human body and the like. The damage of skin tissue not only can cause the damage of human subcutaneous tissue, but also can seriously affect the internal balance of human body. With the advance of the research of preparing bionic materials by tissue engineering, the research of artificial skin is also concerned. Researchers at harbour university as early as 1980 constructed simulated artificial skin for the first time from silica gel and collagen. The artificial skin material can exert the characteristic of being assimilated to the human body when being used for damaging deep skin caused by incised wound, burn and the like, can replace the skin to prevent the loss of water, electrolyte, protein and the like of the human body, and simultaneously can replace the skin to play a barrier function to prevent the invasion of microbes such as external bacteria, viruses and the like and prevent the generation of septicemia. Therefore, the material has important application value for repairing materials when skin is damaged.
At present, the artificial skin dressings on the market mainly crosslink human body affinity materials such as polyamino acid, polysaccharide, silica gel and the like through crosslinking agents such as glutaraldehyde and the like, but the crosslinking agents often contain toxicity, and the affinity of the materials and the human body is often damaged after crosslinking. Particularly, the conventional artificial skin dressing cannot be used like normal skin, needs to be removed after use, and is easy to cause secondary damage to skin wounds. Therefore, the development of biodegradable materials as scaffolds for human body affinity dressings and how to avoid toxic chemical cross-linking are problems to be solved in the field of artificial skin. Patent document (application No. CN201611241308.0) prepares a nanofiber porous membrane by electrospinning collagen and PLLA, and forms a staggered lamination by the collagen and PLLA in equal proportion according to a concentration gradient to form a porous artificial skin of a polylactic acid skeleton, which can absorb the polylactic acid skeleton after reconstruction of human dermal tissue, thereby avoiding secondary surgical extraction. However, collagen and polylactic acid are two materials that are difficult to be compatible, and the patent document describes that a nanofiber porous membrane with pores gradually increased from small to large is formed by synchronously electrospinning a collagen solution and a molten PLLA melt and spraying the solution on a substrate in a staggered and laminated manner. However, when PLLA melt is melted at high temperature for electrospinning, and collagen solution is electrostatically sprayed, the process of electrostatic spraying is very likely to cause collagen inactivation due to high temperature environment, thereby causing the affinity of the prepared porous artificial skin with human body to be greatly reduced.
Disclosure of Invention
In view of the above, an object of the present invention is to provide a wound dressing patch which has a mild preparation process, is compatible with the body material, does not require toxic chemical crosslinking, and can be degraded and absorbed after the human dermal tissue is reconstructed.
According to the technology, the double-layer polylactic acid microporous membrane and the artificial skin dressing layer are constructed on the non-woven fabric support layer, the prepared wound dressing has excellent affinity with a human body, and can be automatically separated and fall off along with reconstruction of human wound dermal tissue and degradation and absorption of polylactic acid, so that the double-layer polylactic acid can be taken out without a secondary operation.
A wound dressing covering comprising:
a support layer;
a first film layer, a second film layer and a wound dressing layer which are sequentially fixed on the supporting layer;
the first film layer can be automatically separated from the second film layer after the second film layer is degraded.
Further, preferably, the wound dressing plaster comprises a supporting layer, wherein a first film layer and a second film layer are arranged on the supporting layer, and a wound dressing layer is arranged on the second film layer; the first film layer is fixedly connected with the supporting layer through one-step coating phase inversion forming; the second film layer is fixedly connected with the first film layer through interfacial fusion after the second film layer is subjected to phase inversion molding of the first film layer and is subjected to secondary coating phase inversion molding; the wound dressing layer is fixedly connected with the second film layer through mutual infiltration of an interface limited space through 3D printing and forming.
Preferably, the first film layer and the second film layer are both made of polylactic acid; the first film layer is a polylactic acid microporous film with a bicontinuous structure; the second film layer is a polylactic acid microporous film with a spherical crystalline stereo composite structure. First rete and second rete have great spatial structure difference, and in the wound dressing subsides use, along with the time extension, polylactic acid is degraded and is absorbed, can promote first rete and second rete autosegregation, realizes falling of wound dressing subsides automation.
Preferably, the first film layer is prepared from levorotatory polylactic acid or dextrorotatory polylactic acid; the second film layer is prepared from a mixture of levorotatory polylactic acid and dextrorotatory polylactic acid. Preferably, the mass ratio of the levorotatory polylactic acid to the dextrorotatory polylactic acid in the mixture is (10-5): 3.
preferably, the first film layer is cured and molded on the surface of the support layer by a coating mode; the second film layer is coated on the surface of the first film layer and is fixedly connected through interfacial fusion; the wound dressing layer is formed on the surface of the second film layer through 3D printing and fixedly connected with each other through an interface limited space in a penetrating mode.
Preferably, the thickness of the first film layer is 20-80 microns, and the average pore diameter of the film layer is 100-500 nanometers; the thickness of the second film layer is 10-50 microns, and the average pore diameter of the film layer is 200-800 nanometers.
Preferably, the supporting layer is a non-woven fabric, the thickness of the non-woven fabric is 10-50 micrometers, and the gram weight of the non-woven fabric is 30-80 grams per square meter; the wound dressing layer includes one or more of a collagen-like and a chitosan-like. More preferably, the mass ratio of the collagen-like substance to the chitosan-like substance is (7-12): 1.
the collagens include but are not limited to collagen, methacrylic anhydride modified collagen, glycidyl methacrylate modified collagen, gelatin, methacrylic anhydride modified gelatin, glycidyl methacrylate modified gelatin, preferably modified gelatin; the chitosan-like includes, but is not limited to, chitosan, carboxymethyl chitosan, hydroxypropyl chitosan, acrylic anhydride modified chitosan, methacrylic anhydride modified chitosan, glycidyl methacrylate modified chitosan, preferably modified chitosan.
The invention also aims to provide a preparation method of the wound dressing paste in any one technical scheme, which comprises the following steps:
(I) coating a material corresponding to the first film layer on the surface of one side of the supporting layer, and curing to form the first film layer on the supporting layer;
(II) coating a material corresponding to the second film layer on the surface of the first film layer, and curing to form the second film layer on the surface of the first film layer;
and (III) loading the wound dressing layer on the surface of the second film layer to obtain the wound dressing paste.
Preferably, the preparation method of the wound dressing patch according to any one of the above technical solutions specifically includes:
(1) preparing a mixed solution of an organic solvent I and water;
(2) preparing a levorotatory polylactic acid/dextrorotatory polylactic acid solution, coating the levorotatory polylactic acid/dextrorotatory polylactic acid solution on the surface of a non-woven fabric, immersing the levorotatory polylactic acid/dextrorotatory polylactic acid solution in the mixed solution in the step (1) for 5-20 seconds, transferring the levorotatory polylactic acid/dextrorotatory polylactic acid solution into pure water for cleaning, and finally drying at the temperature of 20-50 ℃ to construct a first film layer on the surface of a non-woven fabric supporting layer;
(3) preparing a mixed solution of levorotatory polylactic acid and dextrorotatory polylactic acid, coating the mixed solution on the surface of the first film layer prepared in the step (2), transferring the first film layer to a saturated water vapor environment for 1-6 seconds, then transferring the first film layer to deionization for cleaning, and finally drying at the temperature of 20-50 ℃ to construct a second film layer on the surface of the first film layer;
(4) and (4) preparing a collagen-like solution, and printing the collagen-like solution on the surface of the second film layer prepared in the step (3) through 3D printing to obtain the wound dressing.
Preferably, in the step (1), the volume ratio of the organic solvent I to the water is (50-100): 50; the organic solvent I is one or a mixture of N, N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide and N, N-dimethylformamide.
Preferably, in the step (2), the solution of the poly (L-lactic acid)/poly (D-lactic acid) comprises poly (L-lactic acid)/poly (D-lactic acid), an organic solvent II and a template agent; the mass ratio of the levorotatory polylactic acid/dextrorotatory polylactic acid to the organic solvent II is (20-25): 100, respectively; the mass ratio of the template agent to the organic solvent II is (8-18): 100, respectively; the template agent is one or more of polyvinylpyrrolidone, polyoxyethylene and polyethylene glycol; the organic solvent II is one or a mixture of N, N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide and N, N-dimethylformamide. More preferably, the organic solvent II is the same as the organic solvent I. The template agent is one or a mixture of more of polyvinylpyrrolidone, polyoxyethylene and polyethylene glycol.
Preferably, in the step (3), the mixed solution of the levorotatory polylactic acid and the dextrorotatory polylactic acid comprises the levorotatory polylactic acid, the dextrorotatory polylactic acid and an organic solvent III; the mass ratio of the polylactic acid to the organic solvent III is (20-25): 100, respectively; the mass ratio of the levorotatory polylactic acid to the dextrorotatory polylactic acid is (10-5): 3. the organic solvent III is one or a mixture of N, N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide and N, N-dimethylformamide. More preferably, the organic solvent III is the same as the organic solvent II or/and the organic solvent I.
Preferably, in step (4), the collagen-like solution consists of a (collagen-like/chitosan-like) complex and deionized water; the mass ratio of the compound to the deionized water is (5-15): 100.
it is understood that, in order to better achieve the effects of rapid hemostasis, rapid healing, rapid granulation, and infection resistance after the wound dressing is applied, based on the embodiments of the present invention, on the premise that no creative work is made, a person skilled in the art further adds a functional agent, such as a protein active peptide, a protease, an alcohol ether, tannic acid, an antibiotic, glycerol, vaseline, and a traditional Chinese medicine extract, to the collagen-like solution in step (4), so as to achieve all other embodiments of the wound dressing with more effects, which belong to the protection scope of the present invention, and are not repeated in the technical steps of the present invention.
It can be understood that, by adjusting and controlling the simple process parameters such as the time and the speed of the 3D printing in the step (4), and without creative work, dressing layers with different thicknesses, loading densities, drug loading amounts, and the like are obtained to realize all other embodiments of the wound dressing, which belong to the protection scope of the present invention, and are not described in detail in the technical steps of the present invention.
Compared with the prior art, the wound dressing and the preparation method thereof have the following advantages:
in the technical method of the present invention, a first polylactic acid film layer, a second polylactic acid film layer and a wound dressing layer are preferably formed on the surface of a high-strength nonwoven fabric by using a biological polylactic acid material assimilated to a human body and a material having excellent affinity to a human body, such as polyamino acid and polysaccharide. The surface layer of the prepared wound dressing paste is made of human affinity materials such as polyamino acid, polysaccharide and the like, has excellent compatibility with human wounds, and can prevent human immune rejection. The second film layer is a spherical crystalline stereo composite polylactic acid microporous film, and the abundant space confinement structure of the microporous film can provide stable load space for the dressing layer, so that the condition that the stability of the artificial skin is improved by toxic chemical crosslinking in the traditional technology is avoided. The first film layer is a polylactic acid microporous film with a bicontinuous structure, the polylactic acid microporous film and the second film layer can form good fusion connection in the preparation process, meanwhile, the first film layer and the second film layer have large space structure difference, and polylactic acid is assimilated and absorbed by a human body along with time extension in the use process of the wound dressing paste, so that the first film layer and the second film layer can be automatically separated, and the wound dressing paste can automatically fall off. The high-strength non-woven fabric layer provides sufficient mechanical property guarantee for the wound dressing. Furthermore, the non-woven fabric support layer, the first film layer, the second film layer and the wound dressing layer are all of a microporous structure, have good air permeability and moisture retention performance, can effectively prevent the wound from further deterioration caused by oxygen deficiency, softening and the like of skin around the wound, and are beneficial to rapid healing of the wound. In conclusion, the wound dressing paste prepared by the technology has the characteristics of good mechanical strength, air permeability, moisture retention, good biocompatibility, in-vitro degradability and automatic falling-off.
Drawings
FIG. 1 is a scanning electron microscope image of the first film layer of the wound dressing prepared in step (2) of example 1.
FIG. 2 is a scanning electron microscope image of the second film layer of the wound dressing prepared in step (3) of example 1.
FIG. 3 is a scanning electron microscope image of the surface of the wound dressing prepared in step (4) of example 1.
FIG. 4 is a photograph showing the degradation and separation phenomenon of the wound dressing prepared in example 1 in physiological saline.
FIG. 5 is a scanning electron microscope image of the surface of the wound dressing prepared in step (4) of example 2.
Detailed Description
The technical solution of an embodiment of a wound dressing according to the present invention will be described clearly and completely with reference to the accompanying drawings, and it is to be understood that the described embodiment is only a part of the embodiment of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without any inventive step based on the embodiments of the present invention, are within the scope of the present invention.
The L-polylactic acid used in the examples was of type NatureWorks 2003D; the dextrorotatory polylactic acid is Hill science and technology PDLA-05, and the intrinsic viscosity range is 0.30-0.50 dL/g; other polymeric materials, such as gelatin, chitosan, etc., are available from the national medicine, Aladdin and Meclin.
Example 1
Preparing N, N-dimethylacetamide and water into a uniform mixed solution according to a volume ratio of 50: 50;
blending the L-polylactic acid, the polyoxyethylene 10W and the N, N-dimethylacetamide according to the mass ratio of 20:12:100, and stirring for 6 hours at the temperature of 80 ℃ and the rotating speed of 200 r/min; then after vacuum defoaming, uniformly coating the polyester non-woven fabric with the thickness of 30 microns and the gram weight of 50 grams per square meter by using a film coating device with the thickness of 50 microns; then transferring the mixed solution into the mixed solution obtained in the step (1), and keeping the mixed solution for 10 seconds; finally, the membrane is transferred into deionized water for full cleaning and dried at the temperature of 35 ℃, and a first membrane layer is constructed on the surface of the non-woven fabric supporting layer;
blending the levorotatory polylactic acid, the dextrorotatory polylactic acid and the N, N-dimethylacetamide according to the mass ratio of 16:9:100, and stirring for 8 hours at the temperature of 90 ℃ and the rotating speed of 300 r/min; then, after vacuum defoaming, uniformly coating the surface of the first film layer prepared in the step (2) by using a film coating device with a knife edge thickness of 30 microns; subsequently, the mixture is transferred to a saturated water vapor environment for 3 seconds; finally, the membrane is transferred into deionized water for full cleaning and dried at the temperature of 35 ℃, and a second membrane layer is constructed on the surface of the first membrane layer;
step (4), blending methacrylic anhydride modified gelatin, carboxymethyl chitosan and water according to the mass ratio of 12:1:100, and fully and uniformly stirring; and (3) printing the second film layer on the surface of the second film layer prepared in the step (3) by 3D printing at the concentration of 0.5 g/100 square centimeters to obtain the wound dressing patch.
And (3) performing micro-morphology characterization on the first film layer obtained in the step (2) by using a scanning electron microscope, wherein the result is shown in figure 1, and the first film layer is of a uniform double-continuous-hole structure. And (4) performing micro-morphology characterization on the second film layer obtained in the step (3) by using a scanning electron microscope, wherein the result is shown in fig. 2, and the second film layer is a uniform porous stereo composite spherulite structure.
And (3) performing microscopic morphology characterization on the surface of the wound dressing patch obtained in the step (4) by using a scanning electron microscope, wherein the result is shown in fig. 3, so that the prepared wound dressing patch has a good interpenetrating effect on the 3D-printed dressing layer and the polylactic acid stereocomplex spherulite structure of the second film layer, and the performance and the structural stability of the dressing layer in use are ensured. And (3) carrying out stability test on the obtained wound dressing paste, namely taking the wound dressing paste with the same area, respectively placing the wound dressing paste in the air, tap water and physiological saline, and observing the surface of the wound dressing paste and the change of the solution. The result shows that the dressing paste is placed in the air for 6 months, the surface of the dressing paste has no defects such as cracking, and the dressing paste is folded back and forth for 100 times without cracks; the dressing is stuck in tap water and soaked for 2 months, and the surface of the dressing is layered; after the dressing is attached to a normal saline solution and soaked for 20 days, the surface of the dressing is layered, the dressing is continuously soaked, and a broken floating layer appears on the surface of the normal saline solution, as shown in figure 4. The reason is that in a liquid solution, along with the extension of the soaking time, polylactic acid materials of the first film layer and the second film layer of the dressing paste are gradually degraded, meanwhile, due to the larger spatial structure difference between the first polylactic acid film layer and the second polylactic acid film layer, the binding force between the first film layer and the second film layer is gradually weakened along with the time, then the first film layer is separated along with the non-woven fabric and the second film layer along with the dressing layer until the non-woven fabric completely falls off, and the wound dressing paste falls off, so that the wound dressing paste can be removed without a secondary operation in actual use.
Example 2
Preparing N-methyl pyrrolidone and water into a uniform mixed solution according to a volume ratio of 70: 50;
step (2), blending the levorotatory polylactic acid, the polyvinylpyrrolidone K60 and the N-methylpyrrolidone according to the mass ratio of 25:8:100, and stirring for 8 hours at the temperature of 90 ℃ and the rotating speed of 250 r/min; then after vacuum defoaming, uniformly coating the polyester non-woven fabric with the thickness of 10 microns and the gram weight of 80 grams per square meter by using a coating device with the thickness of 80 microns; then transferring the mixed solution into the mixed solution obtained in the step (1), and keeping the mixed solution for 20 seconds; finally, the membrane is transferred into deionized water for full cleaning and dried at the temperature of 20 ℃, and a first membrane layer is constructed on the surface of the non-woven fabric supporting layer;
blending the levorotatory polylactic acid, the dextrorotatory polylactic acid and the N-methyl pyrrolidone according to the mass ratio of 18:6:100, and stirring for 6 hours at the temperature of 85 ℃ and the rotating speed of 300 r/min; then, after vacuum defoaming, uniformly coating the surface of the first film layer prepared in the step (2) by using a film coating device with the thickness of a 10-micrometer knife edge; then transferring the mixture into a saturated water vapor environment for 1 second; finally, the membrane is transferred into deionized water for full cleaning and dried at the temperature of 50 ℃, and a second membrane layer is constructed on the surface of the first membrane layer;
step (4), blending glycidyl methacrylate modified collagen, gelatin (purchased from alatin), acrylic anhydride modified chitosan and water according to the mass ratio of 4:3:1:100, and fully and uniformly stirring; and (3) printing the second film layer on the surface of the second film layer prepared in the step (3) by 3D printing at the concentration of 1 g/100 square centimeters to obtain the wound dressing patch.
And (3) performing micro-topography characterization on the surface of the wound dressing patch obtained in the step (4), and showing that the result is shown in fig. 5, so that the dressing layer printed by 3D and the polylactic acid stereo-composite spherulite structure of the second film layer form good composition, and the performance and the structural stability of the dressing layer in use are ensured.
Example 3
Step (1), preparing dimethyl sulfoxide and water into a uniform mixed solution according to the volume ratio of 100: 50;
blending the L-polylactic acid, the polyethylene glycol 3K and the dimethyl sulfoxide according to the mass ratio of 24:18:100, and stirring for 8 hours at the temperature of 80 ℃ and the rotating speed of 250 r/min; then after vacuum defoaming, uniformly coating the mixture on polyolefin non-woven fabric with the thickness of 50 microns and the gram weight of 50 grams per square meter by using a coating device with the thickness of 20 microns; then transferring the mixed solution into the mixed solution obtained in the step (1), and keeping the mixed solution for 5 seconds; finally, the membrane is transferred into deionized water for full cleaning and dried at the temperature of 50 ℃, and a first membrane layer is constructed on the surface of the non-woven fabric supporting layer;
blending the levorotatory polylactic acid, the dextrorotatory polylactic acid and the dimethyl sulfoxide according to the mass ratio of 14:6:100, and stirring for 6 hours at the temperature of 95 ℃ and the rotating speed of 200 r/min; then, after vacuum defoaming, uniformly coating the surface of the first film layer prepared in the step (2) by using a film coating device with a knife edge thickness of 50 microns; subsequently, the mixture is transferred to a saturated water vapor environment for 6 seconds; finally, the membrane is transferred into deionized water for full cleaning and dried at the temperature of 40 ℃, and a second membrane layer is constructed on the surface of the first membrane layer;
step (4), blending glycidyl methacrylate modified gelatin, chitosan, carboxymethyl chitosan and water according to the mass ratio of 10:0.5:0.5:100, and fully and uniformly stirring; and (4) printing the second film layer on the surface of the second film layer prepared in the step (3) through 3D printing to obtain the wound dressing patch.
Example 4
Preparing N, N-dimethylformamide and water into a uniform mixed solution according to a volume ratio of 85: 50;
blending the levorotatory polylactic acid, polyethylene glycol 1W and N, N-dimethylformamide according to the mass ratio of 22:12:100, and stirring for 6 hours at the temperature of 80 ℃ and the rotating speed of 300 r/min; then after vacuum defoaming, uniformly coating the polyolefin non-woven fabric with the thickness of 40 microns and the gram weight of 60 grams per square meter by using a coating device with the thickness of 40 microns; then transferring the mixed solution into the mixed solution obtained in the step (1), and keeping the mixed solution for 15 seconds; finally, the membrane is transferred into deionized water for full cleaning and dried at the temperature of 40 ℃, and a first membrane layer is constructed on the surface of the non-woven fabric supporting layer;
blending the levorotatory polylactic acid, the dextrorotatory polylactic acid and the N, N-dimethylformamide according to the mass ratio of 15:6:100, and stirring for 10 hours at the temperature of 90 ℃ and the rotating speed of 200 r/min; then, after vacuum defoaming, uniformly coating the surface of the first film layer prepared in the step (2) by using a film coating device with a knife edge thickness of 30 microns; subsequently, the mixture is transferred to a saturated water vapor environment for 3 seconds; finally, the membrane is transferred into deionized water for full cleaning and dried at the temperature of 30 ℃, and a second membrane layer is constructed on the surface of the first membrane layer;
blending collagen, methacrylic anhydride modified gelatin, methacrylic anhydride modified chitosan and water according to the mass ratio of 2:7:1:100, fully and uniformly stirring, and adding 0.05 part by mass of protein active peptide; and (4) printing the second film layer on the surface of the second film layer prepared in the step (3) through 3D printing to obtain the wound dressing patch.
And (4) performing a rabbit wound healing experiment on the wound dressing paste obtained in the step (4), wherein the result shows that after the wound dressing paste is applied, the rabbit wound is well restored, and the wound tissue has no adverse phenomena such as swelling, erythema, bluish purple and the like.
It is understood that, in order to better achieve the effects of rapid hemostasis, rapid healing, rapid granulation, and infection resistance after the wound dressing is applied, based on the embodiments of the present invention, on the premise that no creative work is made, a person skilled in the art further adds a functional agent, such as a protein active peptide, a protease, an alcohol ether, tannic acid, an antibiotic, glycerol, vaseline, and a traditional Chinese medicine extract, to the collagen-like solution in step (4), so as to achieve all other embodiments of the wound dressing with more effects, which belong to the protection scope of the present invention, and are not repeated in the technical steps of the present invention.
It can be understood that, by adjusting and controlling the simple process parameters such as the time and the speed of the 3D printing in the step (4), and without creative work, dressing layers with different thicknesses, loading densities, drug loading amounts, and the like are obtained to realize all other embodiments of the wound dressing, which belong to the protection scope of the present invention, and are not described in detail in the technical steps of the present invention.
The above description of the embodiments is only intended to facilitate the understanding of the method of the invention and its core idea. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims (10)

1. A wound dressing covering, comprising:
a support layer;
a first film layer, a second film layer and a wound dressing layer which are sequentially fixed on the supporting layer;
the first film layer can be automatically separated from the second film layer after the second film layer is degraded.
2. A wound dressing according to claim 1, characterized in that the first and second film layers are both polylactic acid; the first film layer is a polylactic acid microporous film with a bicontinuous structure; the second film layer is a polylactic acid microporous film with a spherical crystalline stereo composite structure.
3. A wound dressing according to claim 1, characterised in that the first film layer is prepared from L-polylactic acid or D-polylactic acid; the second film layer is prepared from a mixture of levorotatory polylactic acid and dextrorotatory polylactic acid.
4. A wound dressing according to claim 1, characterized in that the first film layer is cured and formed on the surface of the supporting layer by coating; the second film layer is coated on the surface of the first film layer and is fixedly connected through interfacial fusion; the wound dressing layer is formed on the surface of the second film layer through 3D printing and fixedly connected with each other through an interface limited space in a penetrating mode.
5. A wound dressing covering according to claim 1, characterised in that the first film layer has a thickness of 20 to 80 microns and an average pore size of 100 to 500 nm; the thickness of the second film layer is 10-50 microns, and the average pore diameter of the film layer is 200-800 nanometers.
6. A wound dressing according to claim 1, wherein the supporting layer is a non-woven fabric, the thickness of the non-woven fabric is 10-50 microns, and the gram weight is 30-80 g/m; the wound dressing layer includes one or more of a collagen-like and a chitosan-like.
7. A preparation method of a wound dressing paste is characterized by comprising the following steps:
(I) coating a material corresponding to the first film layer on the surface of one side of the supporting layer, and curing to form the first film layer on the supporting layer;
(II) coating a material corresponding to the second film layer on the surface of the first film layer, and curing to form the second film layer on the surface of the first film layer;
and (III) loading the wound dressing layer on the surface of the second film layer to obtain the wound dressing paste.
8. A method for preparing a wound dressing according to claim 7, comprising:
(1) preparing a mixed solution of an organic solvent I and water;
(2) preparing a levorotatory polylactic acid/dextrorotatory polylactic acid solution, coating the levorotatory polylactic acid/dextrorotatory polylactic acid solution on the surface of a non-woven fabric, immersing the levorotatory polylactic acid/dextrorotatory polylactic acid solution in the mixed solution in the step (1) for 5-20 seconds, transferring the levorotatory polylactic acid/dextrorotatory polylactic acid solution into pure water for cleaning, finally drying at the temperature of 20-50 ℃, and constructing a first film layer on the surface of a non-woven fabric supporting layer;
(3) preparing a mixed solution of levorotatory polylactic acid and dextrorotatory polylactic acid, coating the mixed solution on the surface of the first film layer prepared in the step (2), transferring the first film layer to a saturated water vapor environment for 1-6 seconds, then transferring the first film layer to deionization for cleaning, finally drying at the temperature of 20-50 ℃, and constructing a second film layer on the surface of the first film layer;
(4) preparing a wound dressing solution, and printing the wound dressing solution on the surface of the second film layer prepared in the step (3) through 3D printing to obtain the wound dressing patch.
9. A preparation method of a wound dressing cover according to claim 8, characterized in that in step (1), the volume ratio of the organic solvent I to water is (50-100): 50; in the step (2), the solution of the L-polylactic acid/the D-polylactic acid comprises the L-polylactic acid/the D-polylactic acid, an organic solvent II and a template agent; the mass ratio of the levorotatory polylactic acid/dextrorotatory polylactic acid to the organic solvent II is (20-25): 100, respectively; the mass ratio of the template agent to the organic solvent II is (8-18): 100, respectively; the template agent is one or more of polyvinylpyrrolidone, polyoxyethylene and polyethylene glycol; in the step (3), the mixed solution of the levorotatory polylactic acid and the dextrorotatory polylactic acid comprises the levorotatory polylactic acid, the dextrorotatory polylactic acid and an organic solvent III; the mass ratio of the polylactic acid to the organic solvent III is (20-25): 100, respectively; the mass ratio of the levorotatory polylactic acid to the dextrorotatory polylactic acid is (10-5): 3; in the step (4), the collagen-like solution consists of a (collagen-like/chitosan-like) compound and deionized water; the mass ratio of the compound to the deionized water is (5-15): 100.
10. a method for preparing a wound dressing according to claim 9, characterized in that organic solvent I, organic solvent II and organic solvent III are each independently one or more of N, N-dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide and N, N-dimethylformamide.
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