CN102526808A - Artificial skin and preparation method thereof - Google Patents
Artificial skin and preparation method thereof Download PDFInfo
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- CN102526808A CN102526808A CN2011104588127A CN201110458812A CN102526808A CN 102526808 A CN102526808 A CN 102526808A CN 2011104588127 A CN2011104588127 A CN 2011104588127A CN 201110458812 A CN201110458812 A CN 201110458812A CN 102526808 A CN102526808 A CN 102526808A
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- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 4
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- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
The invention relates to artificial skin, which is formed by compounding a microporous membrane epidermal layer with piezoelectric conducting performance and a natural high polymer bionic skin corium, wherein the microporous membrane epidermal layer mainly comprises polyvinylidene fluoride and/or a polymer thereof, i.e., polyvinylidene fluoride-trichloroethylene; and the skin corium is a collagen membrane. The preparation method mainly comprises the following steps of: preparing the microporous membrane epidermal layer; polarizing the epidermal layer; and compounding a dermal scaffold and preparing double-layer artificial skin. In the use process of the artificial skin, electric stimulation of which the strength is similar to that of bioelectricity can be generated after binding and extruding, so that healing of a skin wound is facilitated. Meanwhile, the epidermal layer of the artificial skin has a microporous structure of which the size is smaller than those of pathogenic bacteria, so that pathogenic bacteria can be isolated effectively, and infection is prevented; and meanwhile, evaporation of wound moisture can be controlled effectively, and high air permeability and flexibility are achieved.
Description
Technical field
The invention belongs to the bioactive materials field, refer in particular to a kind of artificial skin that possesses the piezoelectricity conductive performance and preparation method thereof.
Background technology
Bio electricity is biological intravital a kind of universal phenomenon, and biological intravital various vital movements all are accompanied by electrical phenomena, and closely related with the metabolism of body.The generation of electrical phenomena is because transcellular ion flow can produce and stride the cell electromotive force in the organism; When cellular layer occurs damagedly, or iuntercellular is when closely connecting resistance and reducing, and cell electromotive force just drive current flows out from these zones; Form electric field, this is the basic feature of cell activities.Research at present shows that various kinds of cell can produce reaction to electric field endogenous or that add, and there is the endogenous electric field in research near being illustrated in the tissue injury district, and cell variation biology such as can under electric field action, divide a word with a hyphen at the end of a line.Biological intravital electric field plays an important role in the Regeneration and Repair process that especially promotes to organize in cell proliferation, differentiation and migration.
Along with progressively going deep into of research; People have found piezoelectric effect in tissues such as bone, blood vessel, muscle; Peterlin etc. discover in 1967 that Kynoar (PVDF) thin film has that piezoelectric property is strong, flexibility is good, degree of accuracy is high, frequency response is wide, response speed is fast, elastic energy density is high, indefatigability and stable performance, good comprehensive performances such as easy processing and preparing.Particularly its acoustic impedance and air, water and biological tissue are very approaching.Therefore PVDF and copolymer p VDF-TrFE (Kynoar-trifluoro-ethylene) thereof are widely used in many technical fields.Importantly said material has good water resistance, and water absorption rate is low, and is nontoxic, implants and do not find in the animal body that any untoward reaction is arranged, more approaching with the intravital various biological piezoelectric effects of people.
Skin has the moisture of maintenance, breathes freely and prevents functions such as bacteria attack as human organ.Receive infringements such as wound, burn, inflammation when skin, especially when large-area skin received grievous injury, wound should be protected immediately.If the shallow-layer or the small size that only are skin are impaired, new skin can be able to regeneration from body.If the large area skin of deep layer receives wound, skin just can not be realized selfreparing, must carry out auto-skin grafting usually, like methods such as stamp skin-grafting, mesh graft, embedding skins.Therefore, how to realize the skin regeneration induction clinically, also have very big challenge.
Summary of the invention
Technical problem to be solved by this invention is: a kind of double-layered artificial skin that possesses the piezoelectricity conductive performance is provided, solves the repairing effect of skin in the prior art and the technical problems such as regeneration of skin histology.
The present invention takes following technical scheme: a kind of artificial skin comprises that the membranaceous epidermal area composite natral of the micropore with piezoelectricity conductive performance macromolecule bionic dermis layer forms; The membranaceous epidermal area of said micropore mainly is made up of Kynoar and/or its copolymer polyvinylidene fluoride-trifluoro-ethylene.Said skin corium is a collagem membrane.
The membranaceous epidermal area thickness of said micropore is 50 ~ 500 μ m, and the pore size scope is 0.05 ~ 0.45 μ m, can effectively control the evaporation of moisture, the intrusion that prevents antibacterial and infection.
Collagen in the said collagem membrane is type i collagen albumen, or is mixed with the collagen-based composite that one or more components mixing form in a spot of III of being selected from Collagen Type VI, chondroitin sulfate, hyaluronic acid, the glycosaminoglycans in the type i collagen albumen.
The method for preparing of the artificial skin of the present invention may further comprise the steps:
Step 1, the membranaceous epidermal area of preparation micropore;
Step 2 is carried out the polarization of epidermal area and is handled;
Step 3; Be compounded to form double-layered artificial skin: the epidermal area of step 2 preparation is put into mould; On the film surface, apply the pre-prepd natural polymer solution of one deck; Lyophilization then, crosslinked is cleaned, promptly on the membranaceous epidermal area of micropore, is formed the natural polymer bionic dermis layer as the dermis scaffold effect, thereby is compounded to form double-layered artificial skin.
In said the 1st step; Use certain organic solvent dissolution PVDF, PVDF and/or PVDF-TrFE; Be enclosed in the container that is full of protective gas; Place fully dissolving in the baking oven of uniform temperature, then pyrosol poured out, place on the thin plate, natural cooling or quenching, PVDF and/or PVDF-TrFE can be separated with solvent, crystallization, film forming; Then film is cleaned repeatedly and remove organic solvent, prepare the membranaceous epidermal area of micropore through drying.Used organic solvent is selected from benzophenone and dimethyl phthalate, diethyl phthalate, N, the double solvents of one or more formations in dinethylformamide, DMAC N,N, the dimethyl sulfoxide; PVDF or PVDF-TrFE, or the mass and size specific concentration after PVDF and the two dissolving of PVDF-TrFE is 5 ~ 40%; Noble gas can be selected from nitrogen, argon and the helium a kind of; Oven temperature can be 180 ~ 250 ℃.
In the said step 2, be that the membranaceous epidermal area of micropore that step 1 prepares is placed in the silicone oil of uniform temperature, the upper and lower surface of epidermal area is covered with electrode, and the processing that polarizes, polarization are handled the back cleaning and removed silicone oil, prepare the membranaceous epidermal area of micropore through drying; The silicone oil temperature is in 100 ~ 130 ℃ scope, and polarizing voltage is 5 ~ 20 MV/m.The electrode that upper and lower surface covers of epidermal area is a silver electrode, keeps voltage up to room temperature again after polarization is handled.
The natural polymer solution for preparing in advance in the said step 3 is collagen solution, is dissolved in spirit of vinegar or is dissolved in the water by the collagen solute to form, and the mass and size specific concentration of collagen solute is 0.1 ~ 2%; Said collagen solute is meant type i collagen albumen, or type i collagen albumen and a small amount of (accounting for solute total mass ratio content is 0 ~ 5%) be selected from that one or more mix the collagen solute of formation in III Collagen Type VI, chondroitin sulfate, hyaluronic acid, the glycosaminoglycans; Said cryodesiccated temperature range is-60 ~-40 ℃; Cross-linking method is chemical crosslinking, and cross-linking agent is selected from one or more in glutaraldehyde, genipin, the carbodiimides, and the mass and size specific concentration of cross-linking agent in cross-linking system is 0.1 ~ 1%.Crosslinking time 12 ~ 24h.
Mould therefor is that corrosion resistant plate processes, and plate central authorities are that the length and width of groove, groove are respectively in the scope of 10 ~ 50cm.
The invention has the beneficial effects as follows: the present invention be based on play an important role in the Regeneration and Repair process that bio electricity promotes tissue and PVDF and PVDF-TrFE piezoelectric effect basis on a kind of double-layered artificial skin that possesses the piezoelectricity conduction effect of developing.Through facts have proved, artificial skin in the process of using, the wrapping extruding that receives, the electricity irritation that can produce similar bio electricity intensity, thus promote the healing of skin wound.Simultaneously, the epidermal area of this artificial skin is microcellular structure, the size of pore structure less than the size of pathogenic bacteria, can effectively isolate pathogenic bacteria, protect from infection; And can effectively control the evaporation of wound moisture, possess air permeability and good and compliance.
The specific embodiment
Double-layered artificial skin of the present invention comprises the epidermal area by Kynoar (PVDF) or its copolymer p VDF-TrFE (Kynoar-trifluoro-ethylene) preparation, and the bionic dermis layer of being processed by natural polymer.Be a kind of double-layered artificial skin that possesses the piezoelectricity conductive performance, can improve the repairing effect of skin effectively, especially induce the regeneration of skin histology.
The membranaceous epidermal area thickness of this micropore is 50 ~ 500 μ m, and the pore size scope is 0.05 ~ 0.45 μ m, can effectively control the evaporation of moisture, the intrusion that prevents antibacterial and infection.The bionic dermis layer of this natural polymer is a collagem membrane.Said collagen is meant type i collagen albumen, or type i collagen albumen with a small amount of (as, content is lower than 5% in the collagen gross mass) III Collagen Type VI, chondroitin sulfate, hyaluronic acid, glycosaminoglycans in one or more mix the collagen-based composite that forms.
The present invention possesses the method for preparing of the double-layered artificial skin of piezoelectricity conductive performance, mainly may further comprise the steps:
Step 1; The membranaceous epidermal area of preparation micropore: use certain organic solvent dissolution PVDF, PVDF and/or PVDF-TrFE; Be enclosed in the container that is full of protective gas; Place fully dissolving in the baking oven of uniform temperature, then pyrosol poured out, place on same pyritous stainless steel metal thin plate or the sheets of glass, natural cooling or quenching, PVDF and/or PVDF-TrFE can be separated with solvent, crystallization, film forming; Then film is cleaned repeatedly and remove organic solvent, prepare the membranaceous epidermal area of micropore through drying.
Step 2, carry out the polarization of epidermal area and handle: the membranaceous epidermal area of micropore that step 1 is prepared is placed in the silicone oil of uniform temperature, and the upper and lower surface of epidermal area is covered with silver electrode, and the processing that polarizes keeps voltage up to room temperature again.With silicone oil abluent and ethanol film is cleaned repeatedly then and remove silicone oil, through the dry membranaceous epidermal area of the micropore that possesses the piezoelectricity conductive performance for preparing.
Step 3: the bionic dermis layer that compound one deck natural polymer is processed on epidermal area; Preparation double-layered artificial skin: the epidermal area of step 2 preparation is put into special-purpose or non-particular manufacturing craft; On the film surface, apply the pre-prepd natural polymer solution of one deck; Lyophilization then, crosslinked is cleaned, promptly on the membranaceous epidermal area of micropore, is formed dermis scaffold (the bionic dermis layer of also processing for natural polymer), thereby prepares double-layered artificial skin.
In the 1st step; Organic solvent is selected from benzophenone and dimethyl phthalate, diethyl phthalate, N; Dinethylformamide, N; The double solvents of one or both formations in N-dimethyl acetylamide, the dimethyl sulfoxide, and be (8 ~ 10) by solvent and solute volume ratio: 1 dissolves.PVDF or PVDF-TrFE, or the mass and size specific concentration after PVDF and the two dissolving of PVDF-TrFE is 5 ~ 40%.Noble gas is selected from nitrogen, argon and the helium a kind of; Oven temperature is 180 ~ 250 ℃, cleans with ether earlier during cleaning and then cleans with ethanol; Preparing the membranaceous epidermal area thickness of micropore is 50 ~ 500 μ m, and the pore size scope is 0.05 ~ 0.45 μ m, can effectively control the evaporation of moisture, the intrusion that prevents antibacterial and infection.
In the said step 2, the silicone oil temperature is in 100 ~ 130 ℃ scope, and polarizing voltage is 5 ~ 20 MV/m.
In the said step 3, particular manufacturing craft is that the thick medical grade corrosion resistant plate of 5mm processes, and plate central authorities are 3mm for the degree of depth of groove and groove, and the length and width of groove are respectively in the scope of 10 ~ 50cm; Natural polymer solution is collagen solution, and solute is a collagen, and solvent is spirit of vinegar or water.Said collagen solute is a type i collagen albumen, or type i collagen albumen and a spot of (as, shared quality percentage composition is less than 5% in the collagen) one or more mix and form collagen-based composites in the III Collagen Type VI, chondroitin sulfate, hyaluronic acid, glycosaminoglycans.In the collagen solution, the mass and size specific concentration of collagen solute is 0.1 ~ 2%.Cryodesiccated temperature range is-60 ~-40 ℃; Cross-linking method is chemical crosslinking, and cross-linking agent is selected from a kind of in glutaraldehyde, genipin, the carbodiimides.In the cross-linking system of cross-linking agent and duplicature formation, the mass and size specific concentration of cross-linking agent is 0.1 ~ 1%, crosslinking time 12 ~ 24h.Be appreciated that indication particular manufacturing craft in the step 3, also can carry out structural design or adjustment, also can select to use other mould of prior art according to concrete needs.
Further specify double-layered artificial skin of the present invention below in conjunction with instance, but not as restriction of the present invention.
Instance 1
The described double-layered artificial skin that possesses the piezoelectricity conductive performance specifically may further comprise the steps:
(1) uses benzophenone and dimethyl phthalate double solvents (volume ratio 8:1) dissolving PVDF; Mass and size specific concentration after the dissolving is 40%; Be enclosed in the container that is full of helium; Place fully dissolving in 200 ℃ of baking ovens,, then pyrosol is poured out, place same pyritous stainless steel metal thin plate, quenching, PVDF and solvent is separated, crystallization, film forming; Then film is cleaned repeatedly and remove organic solvent, prepare the membranaceous epidermal area of micropore through drying.Clean to clean repeatedly with ether cleaning, reuse ethanol earlier then and remove organic solvent, prepare the membranaceous epidermal area of micropore through drying.
(2) polarization of carrying out epidermal area is handled; Be about in the silicone oil that the membranaceous epidermal area of micropore that step (1) prepares is placed in 120 ℃, the upper and lower surface of epidermal area is covered with silver electrode, and processing polarizes; Polarizing voltage is 5 ~ 20 MV/m, keeps voltage up to room temperature.With silicone oil abluent and ethanol film is cleaned repeatedly then and remove silicone oil, prepare the membranaceous epidermal area of micropore through drying.
(3) then the epidermal area of step (2) preparation is put into particular manufacturing craft; On the film surface, applying the pre-prepd mass and size specific concentration of one deck is 1% collagen solution; Lyophilization under-40 ℃ of conditions then, adding mass and size specific concentration are that 0.1% genipin carries out crosslinked 24h; Deionized water cleans repeatedly, promptly on the membranaceous epidermal area of micropore, forms dermis scaffold then, prepares double-layered artificial skin.
Instance 2
The described double-layered artificial skin that possesses the piezoelectricity conductive performance specifically may further comprise the steps:
(1) uses benzophenone and dimethyl phthalate double solvents (9:1) dissolving PVDF and PVDF-TrFE (mass ratio 4:1); The mass and size specific concentration of dissolving back solute is 30%; Be enclosed in the container that is full of helium; Place fully dissolving in 240 ℃ of baking ovens,, then pyrosol is poured out, place same pyritous stainless steel metal thin plate, quenching, solute PVDF and PVDF-TrFE and solvent is separated, crystallization, film forming; Then film is cleaned repeatedly and remove organic solvent, prepare the membranaceous epidermal area of micropore through drying.Clean to clean repeatedly with ether cleaning, reuse ethanol earlier then and remove organic solvent, prepare the membranaceous epidermal area of micropore through drying.
(2) polarization of carrying out epidermal area is then handled; Be about in the silicone oil that the membranaceous epidermal area of micropore that step (1) prepares is placed in 130 ℃, the upper and lower surface of epidermal area is covered with silver electrode, and processing polarizes; Polarizing voltage is 5 ~ 20 MV/m, keeps voltage up to room temperature.With silicone oil abluent and ethanol film is cleaned repeatedly then and remove silicone oil, prepare the membranaceous epidermal area of micropore through drying.
(3) epidermal area of step (2) preparation is put into particular manufacturing craft; On the film surface, applying the pre-prepd mass and size specific concentration of one deck is 1% collagen solution; Lyophilization under-40 ℃ of conditions then, adding mass and size specific concentration are that 1% glutaraldehyde carries out crosslinked 12h; Clean repeatedly, promptly on the membranaceous epidermal area of micropore, form dermis scaffold with deionized water again, prepare double-layered artificial skin.
Patent of the present invention be based on play an important role in the Regeneration and Repair process that bio electricity promotes tissue and PVDF and PVDF-TrFE piezoelectric effect basis on a kind of double-layered artificial skin that possesses the piezoelectricity conduction effect of developing.Through facts have proved, artificial skin receives the electricity irritation that the wrapping extruding can produce similar bio electricity intensity in the process of using, thereby promotes the healing of skin wound.Simultaneously, the epidermal area of this artificial skin is microcellular structure, the size of pore structure less than the size of pathogenic bacteria, can effectively isolate pathogenic bacteria, protect from infection; Simultaneously, can effectively control the evaporation of wound moisture, possess air permeability and good and compliance.
Claims (10)
1. an artificial skin comprises the membranaceous epidermal area of the micropore with piezoelectricity conductive performance and one deck natural polymer bionic dermis layer; The membranaceous epidermal area of said micropore mainly is made up of Kynoar and/or its copolymer polyvinylidene fluoride-trifluoro-ethylene, and said natural polymer bionic dermis layer is the collagen rete.
2. artificial skin as claimed in claim 1 is characterized in that: the membranaceous epidermal area thickness of said micropore is 50 ~ 500 μ m, and the pore size scope is 0.05 ~ 0.45 μ m, can effectively control the evaporation of moisture, the intrusion that prevents antibacterial and infection.
3. artificial skin as claimed in claim 1; It is characterized in that: the collagen in the said collagem membrane is type i collagen albumen, or is mixed with the collagen-based composite that one or more components mixing form in a spot of III of being selected from Collagen Type VI, chondroitin sulfate, hyaluronic acid, the glycosaminoglycans in the type i collagen albumen.
4. like each described artificial skin among the claim 1-3, its preparation method may further comprise the steps:
Step 1, the membranaceous epidermal area of preparation micropore;
Step 2 is carried out the polarization of epidermal area and is handled;
Step 3; Be compounded to form double-layered artificial skin: the epidermal area of step 2 preparation is put into mould; On the film surface, apply the pre-prepd natural polymer solution of one deck; Lyophilization then, crosslinked is cleaned, thereby on the membranaceous epidermal area of micropore, forms the natural polymer bionic dermis layer as the dermis scaffold function.
5. the method for preparing of artificial skin as claimed in claim 4; It is characterized in that: in said the 1st step; With organic solvent dissolution PVDF and/or PVDF-TrFE; Be enclosed in the container that is full of protective gas, place fully dissolving in the baking oven of uniform temperature, then pyrosol poured out, place on the thin plate, natural cooling or quenching, PVDF and/or PVDF-TrFE and solvent is separated, crystallization, film forming; Then film is cleaned and remove organic solvent, make the membranaceous epidermal area of micropore through drying.
6. the method for preparing of artificial skin as claimed in claim 5; It is characterized in that: in said the 1st step; Organic solvent is selected from benzophenone and dimethyl phthalate, diethyl phthalate, N; The double solvents of one or more compositions in dinethylformamide, DMAC N,N, the dimethyl sulfoxide; Mass and size specific concentration after PVDF and/or the PVDF-TrFE dissolving is 5 ~ 40%.
7. the method for preparing of artificial skin as claimed in claim 4; It is characterized in that: in the said step 2; Be that the membranaceous epidermal area of micropore that step 1 prepares is placed in the silicone oil of uniform temperature, the upper and lower surface of epidermal area is covered with electrode, and processing polarizes; Polarization is handled the back cleaning and is removed silicone oil, through the dry membranaceous epidermal area of the micropore with piezoelectricity conductive performance for preparing.
8. the method for preparing of artificial skin as claimed in claim 7, it is characterized in that: in the said step 2, the silicone oil temperature is in 100 ~ 130 ℃ scope, and polarizing voltage is 5 ~ 20 MV/m; The electrode that upper and lower surface covers of epidermal area is a silver electrode, keeps voltage up to room temperature again after polarization is handled.
9. the method for preparing of artificial skin as claimed in claim 4; It is characterized in that: the natural polymer solution for preparing in advance in the said step 3 is collagen solution; Be dissolved in spirit of vinegar or be dissolved in the water by the collagen solute and form, the mass and size specific concentration of collagen solute is 0.1 ~ 2%; Said collagen solute is meant type i collagen albumen, or type i collagen albumen is 0 ~ 5% be selected from III Collagen Type VI, chondroitin sulfate, hyaluronic acid, the glycosaminoglycans one or more and mix the collagen solute that forms with accounting for collagen solute quality than content; Said cryodesiccated temperature range is-60 ~-40 ℃; Cross-linking method is chemical crosslinking, and cross-linking agent is selected from one or more in glutaraldehyde, genipin, the carbodiimides, and the mass and size specific concentration of cross-linking agent in cross-linking system is 0.1 ~ 1%.
10. like the method for preparing of each described artificial skin among the claim 4-9, mould therefor is to be processed by corrosion resistant plate, and plate central authorities are that the length and width of groove, groove are respectively in the scope of 10 ~ 50cm.
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CN102861355A (en) * | 2012-10-12 | 2013-01-09 | 中国人民解放军第三军医大学 | Functional wound dressing capable of accelerating wound healing and preparation method thereof |
CN104068945A (en) * | 2014-06-27 | 2014-10-01 | 深圳齐康医疗器械有限公司 | Artificial skin and preparation method thereof |
CN104984407A (en) * | 2015-07-01 | 2015-10-21 | 世科志扬(北京)医疗科技有限公司 | Tissue engineering artificial skin and preparation method thereof |
CN105031740A (en) * | 2015-07-01 | 2015-11-11 | 世科志扬(北京)医疗科技有限公司 | Waterproof and breathable bionic artificial skin and preparation method thereof |
CN106492278A (en) * | 2016-12-27 | 2017-03-15 | 广东泰宝医疗器械技术研究院有限公司 | A kind of artificial skin and preparation method thereof |
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CN102861355A (en) * | 2012-10-12 | 2013-01-09 | 中国人民解放军第三军医大学 | Functional wound dressing capable of accelerating wound healing and preparation method thereof |
CN104068945A (en) * | 2014-06-27 | 2014-10-01 | 深圳齐康医疗器械有限公司 | Artificial skin and preparation method thereof |
CN104068945B (en) * | 2014-06-27 | 2016-11-16 | 深圳齐康医疗器械有限公司 | A kind of artificial skin and preparation method thereof |
CN104984407A (en) * | 2015-07-01 | 2015-10-21 | 世科志扬(北京)医疗科技有限公司 | Tissue engineering artificial skin and preparation method thereof |
CN105031740A (en) * | 2015-07-01 | 2015-11-11 | 世科志扬(北京)医疗科技有限公司 | Waterproof and breathable bionic artificial skin and preparation method thereof |
CN104984407B (en) * | 2015-07-01 | 2017-11-24 | 北京湃生生物科技有限公司 | A kind of tissue engineering artificial skin and preparation method thereof |
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CN107261205A (en) * | 2017-06-13 | 2017-10-20 | 北京大学口腔医学院 | A kind of powered tissue repair film and preparation method thereof that prevents adhesion |
CN113663134A (en) * | 2021-08-27 | 2021-11-19 | 苏州诺普再生医学有限公司 | Bionic skin stent and preparation method thereof |
CN115444974A (en) * | 2022-10-25 | 2022-12-09 | 中国地质大学(北京) | Electroactive composite patch for treating scald and preparation method and application thereof |
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