CN106474567A - A kind of flexibility artificial skin and preparation method - Google Patents

A kind of flexibility artificial skin and preparation method Download PDF

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Publication number
CN106474567A
CN106474567A CN201611008057.1A CN201611008057A CN106474567A CN 106474567 A CN106474567 A CN 106474567A CN 201611008057 A CN201611008057 A CN 201611008057A CN 106474567 A CN106474567 A CN 106474567A
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braiding layer
layer
hydrogel
preparation
artificial skin
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CN201611008057.1A
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CN106474567B (en
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周佳
厉民
王峥
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Zhejiang Provincial Peoples Hospital
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Zhejiang Provincial Peoples Hospital
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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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/60—Materials for use in artificial skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/52—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A61L2300/104—Silver, e.g. silver sulfadiazine
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A61L2300/414—Growth factors
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602—Type of release, e.g. controlled, sustained, slow
    • A61L2300/604—Biodegradation

Abstract

The present invention relates to flexible artificial skin, including hydrogel layer and one layer of braiding layer, the hydrogel layer is in braiding layer；Braiding layer is high molecular degradable material；Containing Porcine HGF and Nano Silver in hydrogel layer.The invention has the beneficial effects as follows:1) artificial skin material therefor is high molecular degradable material, and material is easy to get, good biocompatibility；2) artificial skin obtained by weaving method is had compared with concrete dynamic modulus, the transport beneficial to nutriment and exchange, and size arbitrarily can be adjusted；3) the fine and close porousness of braiding layer can be changed, realizes the regulation of the physical characteristics such as artificial skin ductility, toughness and mechanical strength by adjusting weaving method；4) atmospheric plasma jet is processed and increased braiding layer fiber surface area, reduces the contact angle of material surface, improves transmissibility and cellular affinity.

Description

A kind of flexibility artificial skin and preparation method
Technical field
The invention belongs to biomedical materials field, more particularly to a kind of flexibility artificial skin and preparation method thereof.
Background technology
Skin, as the maximum organ of people's bulk area, is the natural cover for defense of human body and external environment, with protection, regulation, The effect such as excretion.When the reasons such as inflammation, ulcer, wound, burn, operation cause the defect of skin and exception, gently then impact is suffered from Person's is specious, heavy then initiation infection or a large amount of losses of electrolyte and moisture, causes the death of patient.Particularly with treatment Large skin defect, it is critical only that wound closure, the consumption of minimizing body and the disorder of interior environment as early as possible, prevents harmful substance Invasion, promote surface of a wound skin regeneration.The current defect medically for skin, how using the method for auto-skin grafting, This not only causes the new wound defect in skin donor site, and the restriction being often subject to for skin source.
In order to the injury that defect of skin is brought to body is made up, the skin histology of defect is repaired, is substituted, and various countries scientist is It is devoted to the research of artificial skin.Previously a lot of solutions or product, be by allosome or xenogeneic skin working process Obtained from, there are problems of high processing costs,.With the development of engineering technology, through engineering approaches artificial skin The focus of defect of skin treatment is become, but inreal preferably Graftskin has been applied so far.
The synthetic membrane that also useful different material is made in prior art is used as artificial skin.But such as hyaluronic acid , there is the artificial skin insufficient strength that makes, gas permeability in sodium, shitosan, chondroitin sulfate, the hydrogel of one class of dermatan sulfate Poor problem, and as consumption increases, play the role of to suppress fibroblastic growth.And polyurethane or silicon rubber or poly- second Glycol, or the medical macromolecular materials such as ethylene glycol terephthalate, although solve the strength problem of artificial skin, but close Aqueous not high, slow, RT of often degrading is more long or even non-degradable, causes foreign matter to remain, causes aseptic inflammation, impact Own cells are in field planting and the growth of the surface of a wound, and as these materials can not participate in carrying out physiological metabolism, can only often be used as Outer layer dressing.
Preferably artificial skin need sufficiently flexible, comfortable, not only breathed freely but also permeable, can with the surface of a wound have good fit, While again need certain ductility, toughness and mechanical strength, even for repair juxtra-articular defect of skin when, Adapt to the local skin tension force that joint motion causes to raise and be unlikely to form new wound.In addition, artificial skin needs to carry For good material-Cellular interfaces, be beneficial to itself epithelial cell the regeneration for growing into, promoting neoplastic skin appendicle, Bacterial invasion is resisted, to play the purpose of wound healing, skin function regeneration.
So a kind of process is simple of design, it is easy to volume production, easily preserves, good biocompatibility, it is convenient to apply, cheap Artificial skin, for quick, efficient wound repairing, reduce inconvenience that surface of a wound defect brings to people and harm have very heavy The realistic meaning that wants.
Content of the invention
The purpose of the present invention is to overcome the deficiencies in the prior art, provides a kind of with preferable flexibility, comfortableness, extension Property, toughness and mechanical strength and can air-and water-permeable, antibacterial antivirus, beneficial to epidermal growth migration, be particularly suited for joint attached The surface of a wound of near and trans-articular, while the surface of a wound is protected, promotes the surface of a wound quickly to repair, improves the flexible artificial skin of repairing effect And preparation method thereof.
The purpose of the present invention is achieved through the following technical solutions:This flexibility artificial skin, including hydrogel layer and One layer of braiding layer, the hydrogel layer is in braiding layer；Braiding layer is high molecular degradable material；Containing thin in hydrogel layer The intracellular growth factor and Nano Silver.
The preparation method of this flexibility artificial skin, comprises the steps：
1) high molecular degradable litzendraht wire is made the braiding layer with certain porosity and thickness according to weaving；
2) layer surface is woven with atmospheric plasma state oxygen treatments applied；
3) hydrogel solution containing EGF and Nano Silver is configured；
4) hydrogel solution is applied and is uniformly overlying on braiding layer surface and is solidified, frozen dried.
As preferred：Step 1) in, high molecular degradable material is using PLA (PLA), polyglycolic acid (PGA) or poly- One or more in poly lactic coglycolic acid (PLGA).
As preferred：Step 1) in, weaving can be obtained using He Gelisi weave or the axial weave of two dimension three Braiding layer porosity be 15%-35%, braiding layer thickness be 100-1000 μm.
As preferred：Step 2) in, the temperature of atmospheric plasma state oxygen used is 90-110 DEG C, and flow is 4-12L/ Min, handling duration are 3-10min.
As preferred：Step 3) in, hydrogel material can select in Sodium Hyaluronate, shitosan, chondroitin sulfate Kind, the mol ratio of hydrogel and deionized water is 1:20～1:50.
As preferred：Step 3) in, the mol ratio of EGF, nano-silver ionic and hydrogel material is 10:1: 5000～5:1:1000.
As preferred：Step 4) in, by hydrogel solution with 0.1-2.5mg/cm under aseptic condition2Evenly coated braiding Layer surface, solidifies 1-2h, vacuum freeze drying 6-8h at 4-6 DEG C.
The invention has the beneficial effects as follows:1) artificial skin material therefor is high molecular degradable material, and material is easy to get, biological Compatibility is good；2) artificial skin obtained by weaving method is had compared with concrete dynamic modulus, the transport beneficial to nutriment and exchange, face Product size arbitrarily can be adjusted；3) the fine and close porousness of braiding layer can be changed, realizes artificial skin by adjusting weaving method The regulation of the physical characteristics such as skin ductility, toughness and mechanical strength；4) atmospheric plasma jet is processed and increased braiding layer fibre Dimension table area, reduces the contact angle of material surface, improves transmissibility and cellular affinity；5) EGF in hydrogel Epithelial growth migration growth rate is improve, is conducive to wound repair, silver ion causes artificial skin to have good antibiotic property Can, it is to avoid toxic and side effect of the use of chemical antibacterials to human body, extend the artificial vitrification phase；6) the preparation side of the present invention Method step is simple, and Quality Control is convenient, it is easy to preparation of industrialization.
Description of the drawings
Fig. 1 is braiding layer schematic diagram；
Fig. 2 is to prepare the flexible artificial skin schematic diagram for completing；
The not plasma-treated litzendraht wire configuration of surface of Fig. 3 (amplifies 5000 times)
Litzendraht wire configuration of surface (amplifying 5000 times) after Fig. 4 corona treatment
Before and after Fig. 5 corona treatment, the transmissibility of braiding layer compares
Configuration of surface (amplifying 1000 times) after the braiding layer of the uncoated hydrogel of Fig. 6 and epidermal cell co-cultivation
Configuration of surface (amplifying 1000 times) after the braiding layer of Fig. 7 coating hydrogel and epidermal cell co-cultivation
Description of reference numerals：Braiding layer 1, hydrogel layer 2.
Specific embodiment
The present invention is described further with reference to embodiment.The explanation of following embodiments is only intended to help and understands this Invention.It should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention, also Some improvement and modification can be carried out to the present invention, these improve and modification also falls into the protection domain of the claims in the present invention Interior.
Embodiment 1
1) preparation of litzendraht wire:The PLA long filament of 2 gangs of average fineness 8tex is taken, by 2 section chief's silks and is twisted volume by 300 sth. made by twisting/m Knit line.
2) braiding layer is made:Braiding layer is made using He Gelisi weaving, porosity is 25%, 300 μm of thickness；
3) atmospheric pressure plasma jet treatment:Gases used for helium, gas temperature is 90 DEG C, and flow is 4L/min, during process A length of 4min；
4) hydrogel solution is configured:Sodium Hyaluronate and deionized water are taken according to 1:50 molar ratio is configured to hydrogel Solution, by EGF, nano-silver ionic and hydrogel material according to 10:1:300 molar ratio uniformly mixes；
5) braiding layer coating hydrogel：By hydrogel solution with 1.5mg/cm under aseptic condition2Evenly coated in braiding layer Surface, then solidifies 2h at 4 DEG C, then through 4 DEG C of vacuum freeze dryings 8h.
Embodiment 2
1) preparation of litzendraht wire:The PGA long filament of 2 gangs of average fineness 10tex is taken, by 2 section chief's silks and is twisted volume by 250 sth. made by twisting/m Knit line.
2) braiding layer is made:Braiding layer is made using the axial weaving of two dimension three, porosity is 15%, 400 μm of thickness；
3) atmospheric pressure plasma jet treatment:Gases used for helium, gas temperature is 100 DEG C, and flow is 6L/min, during process A length of 6min；
4) hydrogel solution is configured:Sodium Hyaluronate and deionized water are taken according to 1:30 molar ratio is configured to hydrogel Solution, by EGF, nano-silver ionic and hydrogel material according to 10:1:400 molar ratio uniformly mixes；
5) braiding layer coating hydrogel：By hydrogel solution with 1.0mg/cm under aseptic condition2Evenly coated in braiding layer Surface, then solidifies 1.5h at 4 DEG C, then through 4 DEG C of vacuum freeze dryings 7h.
Embodiment 3
1) preparation of litzendraht wire:The PLGA long filament of 3 gangs of average fineness 6tex is taken, by 3 section chief's silks and is twisted volume by 200 sth. made by twisting/m Knit line.
2) braiding layer is made:Braiding layer is made using He Gelisi weaving, porosity is 30%, 600 μm of thickness；
3) atmospheric pressure plasma jet treatment:Gases used for oxygen, gas temperature is 100 DEG C, and flow is 8L/min, during process A length of 8min；
4) hydrogel solution is configured:Sodium Hyaluronate and deionized water are taken according to 1:40 molar ratio is configured to hydrogel Solution, by EGF, nano-silver ionic and hydrogel material according to 10:1:500 molar ratio uniformly mixes；
5) braiding layer coating hydrogel：By hydrogel solution with 0.8mg/cm under aseptic condition2Evenly coated in braiding layer Surface, then solidifies 1h at 4 DEG C, then through 4 DEG C of vacuum freeze dryings 6h.
Artificial skin performance test is as follows：
1. embodiment 1-3 prepare artificial skin mechanical strength test
1 three groups of artificial skins of table mechanical strength test result (n=6,)
Sample Thickness (μm) Tensile strength (Mpa) Elongation at break (%)
1 301±0.2 0.91±0.05 330±4.5
2 400±0.5 1.03±0.12 424±18.7
3 599±0.9 1.48±0.25 510±2.4
The tensile strength of mechanical strength test result prompting artificial skin and elongation at break with the thickness of artificial skin are in Positive correlation.
2. litzendraht wire configuration of surface relatively as shown in Figure 3 and Figure 4.
3. the transmissibility of braiding layer compares as shown in figure 5, the measure wicking height of braiding layer will obvious height after corona treatment In common braiding layer P<0.05.
4. braiding layer to cellular affinity relatively as shown in Figure 6 and Figure 7.The braiding layer surface adhesion of coating hydrogel is thin Born of the same parents' number is significantly more than common braiding layer surface.

Claims (8)

1. a kind of flexibility artificial skin, it is characterised in that：Including hydrogel layer (2) and one layer of braiding layer (1), the hydrogel layer (2) in braiding layer (1)；Braiding layer (1) is high molecular degradable material；Hydrogel layer contains Porcine HGF in (2) And Nano Silver.
2. a kind of as claimed in claim 1 flexibility artificial skin preparation method, it is characterised in that comprise the steps：
1) high molecular degradable litzendraht wire is made the braiding layer (1) with certain porosity and thickness according to weaving；
2) atmospheric plasma state oxygen treatments applied braiding layer (1) surface is used；
3) hydrogel solution containing EGF and Nano Silver is configured；
4) hydrogel solution is applied and is uniformly overlying on braiding layer (1) surface and is solidified, frozen dried.
3. preparation method according to claim 2, it is characterised in that：Step 1) in, high molecular degradable litzendraht wire is adopted One or more in PLA (PLA), polyglycolic acid (PGA) or Poly(D,L-lactide-co-glycolide (PLGA).
4. preparation method according to claim 2, it is characterised in that：Step 1) in, weaving is compiled using He Gelisi Weave or the axial weave of two dimension three, the braiding layer for obtaining (1) porosity is 15%-35%, and braiding layer (1) thickness is 100- 1000μm.
5. preparation method according to claim 2, it is characterised in that：Step 2) in, atmospheric plasma state oxygen used Temperature is 90-110 DEG C, and flow is 4-12L/min, and handling duration is 3-10min.
6. preparation method according to claim 2, it is characterised in that：Step 3) in, hydrogel material selects hyaluronic acid The mol ratio of the one kind in sodium, shitosan, chondroitin sulfate, hydrogel and deionized water is 1:20～1:50.
7. preparation method according to claim 2, it is characterised in that：Step 3) in, EGF, nano-silver ionic Mol ratio with hydrogel material is 10:1:5000～5:1:1000.
8. preparation method according to claim 2, it is characterised in that：Step 4) in, by hydrogel solution under aseptic condition With 0.1-2.5mg/cm2Evenly coated on 1 surface of braiding layer, at 4-6 DEG C solidify 1-2h, vacuum freeze drying 6-8h.
CN201611008057.1A 2016-11-16 2016-11-16 A kind of flexibility artificial skin and preparation method Active CN106474567B (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108519173A (en) * 2018-03-07 2018-09-11 南京纳铠生物医药科技有限公司 A kind of flexibility stress and humidity sensor, preparation method and application
CN111604940A (en) * 2019-02-22 2020-09-01 本田技研工业株式会社 Artificial epidermis structure
WO2022205645A1 (en) * 2021-04-02 2022-10-06 长春圣博玛生物材料有限公司 Injectable dermal filler and preparation method therefor

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1468634A (en) * 2002-07-15 2004-01-21 上海组织工程研究与开发中心 Double-layered artificial skin and its prepn process
CN1765369A (en) * 2004-10-25 2006-05-03 陈添水 Nano silver gel and its use
CN101234215A (en) * 2008-03-06 2008-08-06 西安组织工程工程技术研究中心 Cell-less composite type artificial skin and preparation thereof
KR20090105379A (en) * 2008-04-02 2009-10-07 주식회사 케이피엠테크 Silk mask sheet containing the silver nanoparticles

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1468634A (en) * 2002-07-15 2004-01-21 上海组织工程研究与开发中心 Double-layered artificial skin and its prepn process
CN1765369A (en) * 2004-10-25 2006-05-03 陈添水 Nano silver gel and its use
CN101234215A (en) * 2008-03-06 2008-08-06 西安组织工程工程技术研究中心 Cell-less composite type artificial skin and preparation thereof
KR20090105379A (en) * 2008-04-02 2009-10-07 주식회사 케이피엠테크 Silk mask sheet containing the silver nanoparticles

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108519173A (en) * 2018-03-07 2018-09-11 南京纳铠生物医药科技有限公司 A kind of flexibility stress and humidity sensor, preparation method and application
CN111604940A (en) * 2019-02-22 2020-09-01 本田技研工业株式会社 Artificial epidermis structure
WO2022205645A1 (en) * 2021-04-02 2022-10-06 长春圣博玛生物材料有限公司 Injectable dermal filler and preparation method therefor

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