CN219423379U - Antibacterial artificial skin - Google Patents

Antibacterial artificial skin Download PDF

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Publication number
CN219423379U
CN219423379U CN202223450317.4U CN202223450317U CN219423379U CN 219423379 U CN219423379 U CN 219423379U CN 202223450317 U CN202223450317 U CN 202223450317U CN 219423379 U CN219423379 U CN 219423379U
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China
Prior art keywords
layer
absorbable
artificial skin
porous
bioactive glass
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CN202223450317.4U
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Inventor
睢小卫
胡艳丽
宋天喜
崔云
何志敏
朱金亮
仇志烨
崔孟龙
吴晶晶
胡刚
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Weifang Aojing Health Technology Co ltd
Aojing Medical Technology Co ltd
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Weifang Aojing Health Technology Co ltd
Aojing Medical Technology Co ltd
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    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The utility model provides antibacterial artificial skin, which belongs to the technical field of artificial skin, and comprises a hypodermis layer, a hypodermis upper layer, an absorbable epidermis layer and a non-absorbable epidermis layer which are sequentially arranged from inside to outside; the hypodermis layer is a spongy porous collagen layer; the dermis upper layer is a porous acellular matrix layer; the porous acellular matrix layer at least comprises a layer of porous acellular matrix membrane; the absorbable epidermis layer comprises two bioactive glass layers and a acellular matrix layer positioned between the two bioactive glass layers; the decellularized matrix layer at least comprises a decellularized matrix membrane; the non-absorbable skin layer is a film layer. The artificial skin provided by the utility model has continuous antibacterial activity, can prevent wound infection, can effectively promote wound healing of soft tissue injury, improves tissue regeneration and repair capability, and accelerates the reconstruction of dermis.

Description

Antibacterial artificial skin
Technical Field
The utility model belongs to the technical field of artificial skin, and particularly relates to antibacterial artificial skin.
Background
The skin is the largest organ of the human body, and the injury can be caused by trauma, burn, diabetic foot, tumor excision operation and the like; at present, a repair method for deeper or large-area skin defects clinically is autologous skin graft or skin flap transplantation, but the autologous skin graft or skin flap transplantation can cause donor area injury; the allogenic skin patch or skin flap transplantation has the problems of immune rejection, safety in use and the like.
The artificial skin can be used as a substitute for autologous skin transplantation, can be used for treating wounds with damaged dermis layers, chronic wounds or burn wounds, has the effects of promoting wound healing, reducing scar formation and the like, overcomes the defect of insufficient autologous skin transplantation resources of large-area burn patients, and gradually occupies the main stream of the market. However, the artificial skin can not establish blood supply with the wound surface in early stage after the transplantation, the bacteriostasis capacity is poor, the infection rate is high after the transplantation, and the occurrence of the infection can not only directly lead to the transplantation failure, but also threaten the life of a patient; at present, the conventional measures of thoroughly cleaning the wound surface, immersing the artificial skin in disinfectant before transplanting, reinforcing dressing change after transplanting, using antibiotics systemically and the like are used for preventing the infection after the artificial skin is transplanted, and the antibacterial capability of the artificial skin cannot be endowed although the effect of preventing the infection after the transplanting is achieved to a certain extent, and a great deal of medicine is easy to cause damage to viscera of a patient and has negative influence on the body of the patient.
Disclosure of Invention
Aiming at one or more technical problems in the prior art, the utility model provides the antibacterial artificial skin, which has continuous antibacterial activity, can prevent wound infection, can effectively promote wound healing of soft tissue injury, improve tissue regeneration and repair capability and accelerate reconstruction of dermis.
The utility model provides an antibacterial artificial skin, which comprises a hypodermis layer, a hypodermis upper layer, an absorbable epidermis layer and a non-absorbable epidermis layer which are sequentially arranged from inside to outside;
the hypodermis layer is a spongy porous collagen layer;
the dermis upper layer is a porous acellular matrix layer; the porous acellular matrix layer at least comprises a layer of porous acellular matrix membrane;
the absorbable epidermis layer comprises two bioactive glass layers and an acellular matrix layer positioned between the two bioactive glass layers; the acellular matrix layer at least comprises one acellular matrix membrane;
the non-absorbable skin layer is a film layer.
Preferably, the thickness of the spongy porous collagen layer is 0.5 mm-5 mm.
Preferably, the thickness of the porous decellularized matrix membrane is 0.02-0.1 mm.
Preferably, the pore diameter of the spongy porous collagen layer is 20-200 μm, and the porosity is more than 90%.
Preferably, the porous decellularized matrix membrane is provided with a plurality of through holes in a thickness direction; the aperture of the through holes is 0.1-1 mm, and the density of the through holes is 9-900/cm 2
Preferably, in the absorbable epidermis layer, the thickness of the bioactive glass layer is 0.02-0.05 mm, and the thickness of the decellularized matrix film is 0.02-0.1 mm.
Preferably, the thickness of the non-absorbable skin layer is 0.1 to 0.25mm.
Preferably, the bioactive glass layer is a nano mesoporous bioactive glass layer.
Preferably, the particle size of the nano mesoporous bioactive glass powder in the nano mesoporous bioactive glass layer is not more than 50 mu m, and the pore diameter is 5-20 nm.
Preferably, the non-absorbable skin layer is a silicone rubber film or a polyvinyl alcohol film.
Compared with the prior art, the utility model has at least the following beneficial effects:
the dermis upper layer is a porous decellularized matrix layer, is similar to a natural dermis structure, has strong mechanical properties, and can accelerate reconstruction of dermis; the hypodermis layer is a spongy porous collagen layer, which is beneficial to hemostasis and fibroblast and capillary blood tube growth and is beneficial to reconstruction of the hypodermis layer; the absorbable epidermis layer comprises two bioactive glass layers and a cell-free matrix layer positioned between the two bioactive glass layers, can promote cell adhesion and proliferation, improve tissue regeneration and repair capability, has continuous antibacterial activity, can promote wound healing of soft tissue injury while preventing wound infection, and can play a role similar to that of epidermis stratum corneum in the later stage; the non-absorbable epidermis layer film layer can play roles in preventing moisture loss, isolating, preventing bacteria invasion and the like.
The upper dermis layer and the lower dermis layer of the artificial skin provided by the utility model adopt materials with different sources and processes to control degradation and tissue reconstruction time, and the degradation and tissue replacement time can be controlled through different layering layers, so that different clinical requirements are met.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present utility model, the drawings required for the description of the embodiments will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present utility model, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic view of the structure of an antimicrobial artificial skin provided by the utility model;
in the figure, the 1-subdermal layer, the 2-dermal upper layer, the 31-bioactive glass layer, the 32-acellular matrix layer, the 4-non-absorbable epidermal layer.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present utility model more apparent, the embodiments described below will be clearly and completely described in conjunction with the technical solutions of the embodiments of the present utility model, and it is apparent that the described embodiments are some, but not all, embodiments of the present utility model, and all other embodiments obtained by persons of ordinary skill in the art without making any inventive effort based on the embodiments of the present utility model are within the scope of protection of the present utility model.
As shown in fig. 1, the present utility model provides an antimicrobial artificial skin comprising a sub-dermal layer 1, an upper dermal layer 2, an absorbable epidermal layer 3 and a non-absorbable epidermal layer 4, which are sequentially arranged from inside to outside;
the hypodermis layer 1 is a spongy porous collagen layer;
the dermis upper layer 2 is a porous decellularized matrix layer; the porous acellular matrix layer at least comprises a layer of porous acellular matrix membrane;
the absorbable epidermal layer 3 comprises two bioactive glass layers 31 and a decellularized matrix layer 32 positioned between the two bioactive glass layers 31; the acellular matrix layer 32 comprises at least one acellular matrix membrane;
the non-absorbable skin layer 4 is a film layer.
The dermis upper layer is a porous decellularized matrix layer, is similar to a natural dermis structure, has strong mechanical properties, and can accelerate reconstruction of dermis; the hypodermis layer is a spongy porous collagen layer, which is beneficial to hemostasis and fibroblast and capillary blood tube growth and is beneficial to reconstruction of the hypodermis layer; the absorbable epidermis layer comprises two bioactive glass layers and a cell-free matrix layer positioned between the two bioactive glass layers, can promote cell adhesion and proliferation, improve tissue regeneration and repair capability, has continuous antibacterial activity, can promote wound healing of soft tissue injury while preventing wound infection, and can play a role similar to that of epidermis stratum corneum in the later stage; the non-absorbable epidermis layer film layer can play roles in preventing moisture loss, isolating, preventing bacteria invasion and the like.
The spongy porous collagen layer is obtained by freeze drying a collagen solution; the collagen solution is prepared by mixing type I collagen and acetic acid solution; the mass fraction of acetic acid in the acetic acid solution is 4 to 8% (for example, may be 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5% or 8%).
It should be noted that, the preparation method of the type I collagen in the present utility model refers to patent CN114732954a, and specifically includes: s1: removing fat and fascia on the beef achilles tendon with certain quality, cleaning and freezing; s2: cutting frozen beef achilles tendon to a thickness of about 0.8 mm; s3: soaking the slice cut by the S2 in sodium bicarbonate solution with the mass fraction of 1.0-1.5% for 12-24 h, and then cleaning the slice with purified water for degreasing for a plurality of times; s4: adding the sheet degreased by the step S3 into an acid solution with the pH value of 1-3, carrying out enzymolysis for 48-96 hours at the temperature of 0-25 ℃, and removing terminal peptide to obtain an enzymolysis solution; the acid solution is prepared from one or more of acetic acid, citric acid and phosphoric acid; in the utility model, the acid solution with the pH value of 2 is preferable for enzymolysis, because the optimal condition for activating the added pepsin is normal temperature, the pH value is between 2 and 3, the enzymolysis is carried out for 48 to 96 hours, preferably 96 hours at normal temperature, the enzymolysis is thorough, and the yield is high; s5: centrifuging the enzymolysis liquid obtained in the step S4 by using a centrifuge, taking supernatant, and separating out collagen floccule by using a salt solution, wherein the salt is one or more of sodium chloride, potassium chloride, sodium carbonate and potassium carbonate, and the salt solution is supersaturated salt solution; s6: adding the white floccule obtained in the step S5 into a dialysis bag for dialysis, so as to ensure that the environmental change of the dialysis external liquid is mild and avoid the excessive change of the dialysis external liquid, thereby causing irreversible precipitation of collagen in the dialysis internal liquid, and finally, using purified water for dialysis to finish the purification of the collagen by adopting a gradient dialysis mode, such as gradually reducing the concentration of acetic acid in the external liquid; the manner of gradient dialysis may be, for example: firstly, placing a dialysis bag in 45L of pH=3 dialysate for dialysis for 4 days, wherein the dialysis temperature is 15+/-3 ℃, and 1 dialysate is changed every 2 days; then placing the dialysis bag in 45L of pH=4 dialysate for dialysis for 5 days, wherein the dialysis temperature is 15+/-3 ℃, and the dialysate is changed for 1 time every 1 day; placing the dialysis bag in 45L of purified water for dialysis for 6 days, wherein the dialysis temperature is 15+/-3 ℃, and the dialysate is changed for 3 times a day, once in the morning, in the middle and at night; in the present utility model, the dialysate of ph=3 and the dialysate of ph=4 are, for example, acetic acid solutions prepared from acetic acid and purified water, and the preparation of the dialysate of ph=3 may be, for example: adding 45000mL of purified water into a dialysis tank, accurately taking 146.694mL of acetic acid by using a measuring cylinder and a pipetting gun, and uniformly stirring to obtain an acetic acid solution with pH=3; the formulation of the dialysate at ph=4 can be, for example: adding 45000mL of purified water into a dialysis tank, accurately taking 1.479mL of acetic acid by a liquid-transferring gun, adding into the dialysis tank, and uniformly stirring to obtain an acetic acid solution with pH=4; s7: placing the collagen gel with certain mass and solid content produced in the step S6 into a homogenizer, adding water with certain mass to prepare a collagen solution with the concentration of 0.5-0.9%, wherein the homogenizing frequency is 20-50 Hz, and the time is 15-60min; s8: and (3) freeze-drying the homogenized collagen gel in the step (S7) to obtain the type I collagen with uniform texture.
According to some preferred embodiments, the spongy porous collagen layer has a thickness of 0.5mm to 5mm (e.g., may be 0.5mm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm, 4.5mm, or 5 mm).
According to some preferred embodiments, the porous decellularized matrix membrane has a thickness of 0.02 to 0.1mm (e.g., can be 0.02mm, 0.03mm, 0.04mm, 0.05mm, 0.06mm, 0.07mm, 0.08mm, 0.09mm, or 0.1 mm).
According to some preferred embodiments, the spongy porous collagen layer has a pore size of 20 to 200 μm (e.g., may be 20 μm, 50 μm, 60 μm, 80 μm, 100 μm, 120 μm, 140 μm, 160m, 180 μm or 200 μm), with a porosity of greater than 90%.
According to some preferred embodiments, the porous decellularized matrix membrane is provided with a plurality of through holes in the thickness direction; the aperture of the through holes is 0.1-1 mm and 0.1mm, 0.2mm, 0.4mm, 0.8mm or 1 mm), and the density of the through holes is 9-900 pieces/cm 2 (e.g., may be 9/cm) 2 10 pieces/cm 2 50 pieces/cm 2 100 pieces/cm 2 150 pieces/cm 2 200 pieces/cm 2 250 pieces/cm 2 300 pieces/cm 2 350 pieces/cm 2 400 pieces/cm 2 450 pieces/cm 2 500 pieces/cm 2 550 pieces/cm 2 600 pieces/cm 2 650 pieces/cm 2 700 pieces/cm 2 750/cm 2 800 pieces/cm 2 850 pieces/cm 2 Or 900 pieces/cm 2 )。
It should be noted that, in the present utility model, the density of the through holes is adjusted according to the aperture of the through holes, and the larger the aperture is, the smaller the density of the through holes is; for example, when the hole diameter of the through holes is 0.1mm, the density of the through holes is not more than 900 pieces/cm 2 The preparation method is finished; when the aperture of the through hole is 1mmThe density of the through holes is not more than 9/cm 2 And the method can be specifically adjusted according to actual requirements.
According to some preferred embodiments, in the absorbable skin layer, the bioactive glass layer 31 has a thickness of 0.02 to 0.05mm (e.g., may be 0.02mm, 0.03mm, 0.04mm, or 0.05 mm), and the decellularized matrix film has a thickness of 0.02 to 0.1mm (e.g., may be 0.02mm, 0.03mm, 0.04mm, 0.05mm, 0.06mm, 0.07mm, 0.08mm, 0.09mm, or 0.1 mm).
According to some preferred embodiments, the thickness of the non-absorbable skin layer 4 is 0.1 to 0.25mm (e.g., may be 0.1mm, 0.12mm, 0.14mm, 0.16mm, 0.18mm, 0.2mm, 0.22mm, 0.24mm, or 0.25 mm).
According to some preferred embodiments, the bioactive glass layer 31 is a nano-mesoporous bioactive glass layer.
According to some preferred embodiments, the particle size of the nano-mesoporous bioactive glass powder in the nano-mesoporous bioactive glass layer is not more than 50 μm, and the pore size is 5 to 20nm (for example, may be 5nm, 8nm, 10nm, 12nm, 15nm, 18nm or 20 nm).
According to some preferred embodiments, the non-absorbable skin layer 4 is a silicone rubber film or a polyvinyl alcohol film.
In order to more clearly illustrate the technical scheme and advantages of the present utility model, the present utility model will be further described below with reference to examples.
The materials and the reagents in the utility model can be obtained by direct purchase or self-synthesis in the market, and the specific model is not limited.
Example 1
An antibacterial artificial skin comprises a hypodermis layer 1, a hypodermis layer 2, an absorbable epidermis layer 3 and a non-absorbable epidermis layer 4 which are sequentially arranged from inside to outside; the thickness of the spongy porous collagen layer of the hypodermis layer 1 is 2.5mm, the aperture is 100 mu m, and the porosity is 93%; the dermis upper layer 2 is a three-layer porous acellular matrix film, the thickness of the single-layer porous acellular matrix film is 0.1mm, the porous acellular matrix film is provided with a plurality of through holes along the thickness direction, and the through holes are formed in the porous acellular matrix filmThe aperture is 0.1mm, and the density of the through holes is 500 pieces/cm 2 The method comprises the steps of carrying out a first treatment on the surface of the The absorbable epidermis layer comprises two layers of nano mesoporous bioactive glass layers 31 and a decellularized matrix layer 32 positioned between the two layers of nano mesoporous bioactive glass layers 31; the decellularized matrix layer 32 is a three-layer decellularized matrix film, and the thickness of a single-layer decellularized matrix film is 0.05mm; the thickness of the single-layer nano mesoporous bioactive glass layer 31 is 0.05mm, the particle size of the nano mesoporous bioactive glass powder is 40 mu m, the pore diameter is 10nm, and the thickness of the non-absorbable surface layer 4 is 0.15mm.
Example 2
An antibacterial artificial skin comprises a hypodermis layer 1, a hypodermis layer 2, an absorbable epidermis layer 3 and a non-absorbable epidermis layer 4 which are sequentially arranged from inside to outside; the thickness of the spongy porous collagen layer of the hypodermis layer 1 is 2.5mm, the pore diameter is 20 mu m, and the porosity is 91%; the dermis upper layer 2 is a layer of porous acellular matrix membrane, the thickness of a single layer of porous acellular matrix membrane is 0.02mm, the porous acellular matrix membrane is provided with a plurality of through holes along the thickness direction, the aperture of the through holes is 0.2mm, and the density of the through holes is 200 pieces/cm 2 The method comprises the steps of carrying out a first treatment on the surface of the The absorbable epidermis layer comprises two layers of nano mesoporous bioactive glass layers 31 and a decellularized matrix layer 32 positioned between the two layers of nano mesoporous bioactive glass layers 31; the decellularized matrix layer 32 is a two-layer decellularized matrix film with a single-layer decellularized matrix film thickness of 0.02mm; the thickness of the single-layer nano mesoporous bioactive glass layer 31 is 0.02mm, the particle size of the nano mesoporous bioactive glass powder is 40 mu m, the pore diameter is 5nm, and the thickness of the non-absorbable surface layer 4 is 0.15mm.
Example 3
An antibacterial artificial skin comprises a hypodermis layer 1, a hypodermis layer 2, an absorbable epidermis layer 3 and a non-absorbable epidermis layer 4 which are sequentially arranged from inside to outside; the thickness of the spongy porous collagen layer of the hypodermis layer 1 is 5mm, the pore diameter is 200 mu m, and the porosity is 93%; the dermis upper layer 2 is a two-layer porous acellular matrix film, the thickness of a single-layer porous acellular matrix film is 0.1mm, a plurality of through holes are formed in the porous acellular matrix film along the thickness direction, the aperture of each through hole is 1mm, and the density of each through hole is 9/cm 2 The method comprises the steps of carrying out a first treatment on the surface of the The absorbable skin layer comprises two layersA nano mesoporous bioactive glass layer 31 and a decellularized matrix layer 32 positioned between the two nano mesoporous bioactive glass layers 31; the decellularized matrix layer 32 is a two-layer decellularized matrix film with a single-layer decellularized matrix film thickness of 0.1mm; the thickness of the single-layer nano mesoporous bioactive glass layer 31 is 0.05mm, the particle size of the nano mesoporous bioactive glass powder is 40 mu m, the pore diameter is 20nm, and the thickness of the non-absorbable surface layer 4 is 0.25mm.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present utility model, and are not limiting; although the utility model has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present utility model.

Claims (10)

1. An antibacterial artificial skin is characterized by comprising a hypodermis layer, a hypodermis upper layer, an absorbable epidermis layer and a non-absorbable epidermis layer which are sequentially arranged from inside to outside;
the hypodermis layer is a spongy porous collagen layer;
the dermis upper layer is a porous acellular matrix layer; the porous acellular matrix layer at least comprises a layer of porous acellular matrix membrane;
the absorbable epidermis layer comprises two bioactive glass layers and an acellular matrix layer positioned between the two bioactive glass layers; the acellular matrix layer at least comprises one acellular matrix membrane;
the non-absorbable skin layer is a film layer.
2. The antimicrobial artificial skin according to claim 1, wherein the thickness of the spongy porous collagen layer is 0.5mm to 5mm.
3. The antimicrobial artificial skin according to claim 1, wherein the porous decellularized matrix film has a thickness of 0.02 to 0.1mm.
4. The antimicrobial artificial skin according to claim 1, wherein the spongy porous collagen layer has a pore size of 20 to 200 μm and a porosity of more than 90%.
5. The antimicrobial artificial skin according to claim 1, wherein the porous decellularized matrix film is provided with a plurality of through holes in a thickness direction; the aperture of the through holes is 0.1-1 mm, and the density of the through holes is 9-900/cm 2
6. The antimicrobial artificial skin according to claim 1, wherein the thickness of the bioactive glass layer in the absorbable epidermal layer is 0.02 to 0.05mm and the thickness of the decellularized matrix film is 0.02 to 0.1mm.
7. The antimicrobial artificial skin according to claim 1, wherein the non-absorbable skin layer has a thickness of 0.1 to 0.25mm.
8. The antimicrobial artificial skin of claim 1, wherein the bioactive glass layer is a nano-mesoporous bioactive glass layer.
9. The antimicrobial artificial skin according to claim 8, wherein the nano mesoporous bioactive glass powder in the nano mesoporous bioactive glass layer has a particle size of not more than 50 μm and a pore size of 5 to 20nm.
10. The antimicrobial artificial skin of claim 1, wherein the non-absorbable skin layer is a silicone rubber film or a polyvinyl alcohol film.
CN202223450317.4U 2022-12-21 2022-12-21 Antibacterial artificial skin Active CN219423379U (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202223450317.4U CN219423379U (en) 2022-12-21 2022-12-21 Antibacterial artificial skin

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202223450317.4U CN219423379U (en) 2022-12-21 2022-12-21 Antibacterial artificial skin

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