CN111700713A - Artificial skin - Google Patents
Artificial skin Download PDFInfo
- Publication number
- CN111700713A CN111700713A CN202010588871.5A CN202010588871A CN111700713A CN 111700713 A CN111700713 A CN 111700713A CN 202010588871 A CN202010588871 A CN 202010588871A CN 111700713 A CN111700713 A CN 111700713A
- Authority
- CN
- China
- Prior art keywords
- artificial skin
- layer
- collagen
- skin
- antibacterial
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 210000003491 skin Anatomy 0.000 claims abstract description 86
- 102000008186 Collagen Human genes 0.000 claims abstract description 46
- 108010035532 Collagen Proteins 0.000 claims abstract description 46
- 229920001436 collagen Polymers 0.000 claims abstract description 46
- 210000002615 epidermis Anatomy 0.000 claims abstract description 34
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 29
- 230000002500 effect on skin Effects 0.000 claims abstract description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000000741 silica gel Substances 0.000 claims abstract description 16
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 16
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 13
- 230000004761 fibrosis Effects 0.000 claims abstract description 13
- 239000012528 membrane Substances 0.000 claims abstract description 11
- 208000027932 Collagen disease Diseases 0.000 claims abstract description 6
- 210000004207 dermis Anatomy 0.000 claims description 23
- 239000000126 substance Substances 0.000 claims description 12
- 238000004132 cross linking Methods 0.000 claims description 8
- 239000011148 porous material Substances 0.000 claims description 7
- 239000000835 fiber Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 229910052581 Si3N4 Inorganic materials 0.000 claims description 5
- 239000002994 raw material Substances 0.000 claims description 5
- HQVNEWCFYHHQES-UHFFFAOYSA-N silicon nitride Chemical group N12[Si]34N5[Si]62N3[Si]51N64 HQVNEWCFYHHQES-UHFFFAOYSA-N 0.000 claims description 5
- 229920000728 polyester Polymers 0.000 claims description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 3
- 239000004745 nonwoven fabric Substances 0.000 claims description 3
- 108010022355 Fibroins Proteins 0.000 claims description 2
- 229920002413 Polyhexanide Polymers 0.000 claims description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 2
- 229920002635 polyurethane Polymers 0.000 claims description 2
- 239000004814 polyurethane Substances 0.000 claims description 2
- 229910052709 silver Inorganic materials 0.000 claims description 2
- 239000004332 silver Substances 0.000 claims description 2
- 230000003115 biocidal effect Effects 0.000 claims 1
- 238000002054 transplantation Methods 0.000 abstract description 6
- 230000008439 repair process Effects 0.000 abstract description 4
- 239000010410 layer Substances 0.000 description 24
- 206010052428 Wound Diseases 0.000 description 18
- 208000027418 Wounds and injury Diseases 0.000 description 18
- 230000007547 defect Effects 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 6
- 108010025899 gelatin film Proteins 0.000 description 5
- 230000035876 healing Effects 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 210000002950 fibroblast Anatomy 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229920002379 silicone rubber Polymers 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 241000700159 Rattus Species 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 206010062575 Muscle contracture Diseases 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 208000006111 contracture Diseases 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 238000009581 negative-pressure wound therapy Methods 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 239000002344 surface layer Substances 0.000 description 2
- YWMSSKBMOFPBDM-UHFFFAOYSA-N 4-carbamoylbenzenesulfonyl chloride Chemical compound NC(=O)C1=CC=C(S(Cl)(=O)=O)C=C1 YWMSSKBMOFPBDM-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 238000009631 Broth culture Methods 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 108010080379 Fibrin Tissue Adhesive Proteins 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 206010053615 Thermal burn Diseases 0.000 description 1
- 206010048038 Wound infection Diseases 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 229960001656 amikacin sulfate Drugs 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000000512 collagen gel Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000005251 gamma ray Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 210000001126 granulation tissue Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 206010020488 hydrocele Diseases 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 229920006264 polyurethane film Polymers 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 229960001516 silver nitrate Drugs 0.000 description 1
- 229960003600 silver sulfadiazine Drugs 0.000 description 1
- UEJSSZHHYBHCEL-UHFFFAOYSA-N silver(1+) sulfadiazinate Chemical compound [Ag+].C1=CC(N)=CC=C1S(=O)(=O)[N-]C1=NC=CC=N1 UEJSSZHHYBHCEL-UHFFFAOYSA-N 0.000 description 1
- 231100000019 skin ulcer Toxicity 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000028016 temperature homeostasis Effects 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000003357 wound healing promoting agent Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS 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
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/10—Hair or skin implants
- A61F2/105—Skin implants, e.g. artificial skin
Landscapes
- Health & Medical Sciences (AREA)
- Transplantation (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
The invention discloses novel artificial skin which is composed of an epidermal layer and a dermal layer, wherein the epidermal layer is an antibacterial silica gel membrane with enhanced strength, and the dermal layer is a three-dimensional porous structure composed of denatured collagen and fibrosis collagen. The artificial skin has good antibacterial effect, can be used together with the self-reticulate skin grafting to realize one-step transplantation treatment so as to greatly shorten the operation time, avoid secondary operation treatment and shorten the skin repair time, thereby having good application value and market popularization prospect.
Description
Technical Field
The invention belongs to the field of medical instruments, and particularly relates to a novel artificial skin.
Background
The skin is the largest organ of the human body, plays an important role in protecting the internal environment of the organism, resisting external stimulation and invasion of pathogenic bacteria, and has the functions of water retention, secretion, excretion, sensation, thermoregulation, immunity and the like. When large-area skin is damaged due to accidental burns, skin ulcers and the like, the body fluid is easy to lose and external bacteria invade and infect, and the original shape and function of the body fluid are difficult to maintain. If the skin is not protected in time, shock can be caused, and the life safety of the patient is threatened. To solve this problem, people usually use artificial skin to protect patients with burns and the like.
Most of the currently used artificial skins have an epidermis layer and a dermis layer, wherein the epidermis layer adopts a compact silica gel membrane, and the dermis layer adopts three-dimensional porous collagen. After the artificial skin is implanted into the burn defect part, the rest of the fibroblasts and capillaries of the wound base or the surrounding tissues can enter the artificial skin to repair the burn wound, meanwhile, the artificial skin is gradually decomposed to finally form tissues similar to dermis, and the process usually needs about 2-4 weeks. After a good wound surface tissue is formed, the silica gel membrane of the epidermis is also required to be removed, and the autologous epidermis is transplanted in the 2 phase to heal the skin. That is, the existing artificial skin treatment needs 2 operations, namely, the artificial skin is transplanted first, and the autologous epidermis is transplanted after the dermal wound is repaired for 2-4 weeks. Thus, it takes at least 4 weeks or more from the skin wound to the healing of the epidermis. Because the epidermis plays an extremely important role in pathogenic bacteria invasion and the like, early healing plays an extremely important role in improving the life-saving rate. In addition, general maladies in patients with extensive burns are likely to cause infections. Therefore, the development of artificial skin having antibacterial ability and capable of being transplanted simultaneously with the autologous epidermis is an important issue in the development of new artificial skin in the world.
Disclosure of Invention
The invention aims to provide a novel artificial skin which has good antibacterial effect and can effectively avoid wound infection; and the artificial skin grafting device can be used together with the autologous epidermis to realize one-step transplantation treatment, and avoids the defect that the prior art needs to transplant the artificial skin first and then transplant the autologous epidermis in 2-stage operation treatment, so that the life-saving rate of patients with large-area burn is improved, and the artificial skin grafting device has good application value and market popularization prospect.
In order to achieve the purpose, the invention adopts the following technical scheme:
an artificial skin comprises a surface layer and a dermis layer, wherein the surface layer is an antibacterial silica gel film with enhanced strength, can allow fresh oxygen and water vapor to pass through and can prevent bacteria from entering; the dermis is a three-dimensional porous structure formed by denatured collagen and fibrosis collagen, wherein the denatured collagen can promote fibroblasts and vascular cells to enter the artificial skin at an early stage and promote a wound surface to form a dermal tissue, and the fibrosis collagen can improve the mechanical strength of the artificial skin and prevent scar contracture. When the artificial skin is used together with the autologous epidermis, the crosslinking degree of the denatured collagen and the fibrosis collagen is controlled, so that the artificial skin can be quickly degraded into collagen gel while the proper mechanical strength is kept, and the epidermal growth and healing are further promoted.
The antibacterial silica gel membrane with enhanced strength is prepared by attaching reticular polyester fiber, non-woven fabric, silk fibroin or polyurethane to one surface of the silica gel membrane close to the corium layer to achieve strength enhancement, and adding antibacterial substances to achieve an anti-infection effect (the antibacterial substances can be uniformly coated on the surface of the silica gel membrane or can be uniformly mixed with silicon rubber to prepare the silica gel membrane). The antibacterial substance can be silver-containing substance such as silver nanoparticles, silver nitrate, silver sulfadiazine, tetracycline, gentamicin, PHMB, chlorhexidine or silicon nitride.
The dermis layer is prepared by mixing denatured collagen and fibrosis collagen, and then freeze-drying and physically crosslinking (such as vacuum heating crosslinking), wherein the crosslinking degree is controlled to be 20-50%, the porosity is 80-98%, and the pore diameter is 50-250 μm, so that the wound healing is promoted, the granulation growth of the wound surface is promoted, and the one-step transplantation of the artificial skin and the autologous epidermis is realized. Wherein the proportion of the denatured collagen is 10-90wt%, preferably 30-70 wt%.
The denatured collagen is obtained by chemical or physical treatment, preferably by heating at 37-120 deg.C, more preferably 50-80 deg.C. The fibrillating collagen is an insoluble collagen component obtained by neutralizing collagen with a buffer. The raw materials for preparing the two are collagen with the terminal peptides removed.
The thickness of the epidermis layer of the artificial skin obtained by the invention is 3-500 mu m, the thickness of the dermis layer is 1-5mm, preferably 2-3mm, and the strength of the artificial skin is 2 × 105-10×105dyne/cm2So that the Wound healing promoting agent can be used together with a Negative Pressure Therapy (NPWT) technology for wounds and the like, the growth of granulation tissues of Wound surfaces is accelerated, and early healing is promoted.
The artificial skin is also provided with a plurality of pore passages penetrating through the epidermis layer and the dermis layer so as to promote the contact between the wound surface and the artificial skin, facilitate the drainage of the hydrocele of the wound and realize the early wound surface repair; may also be advantageously used with NPWT. The cross section of the pore canal can be round or square, and the diameter is 1-5mm, preferably 2-3 mm.
The obtained artificial skin can be sterilized by EOG, gamma ray, etc., preferably by supercritical CO at 32-35 deg.C and 7-9 atm2Sterilizing to maintain the three-dimensional structure and collagen properties of the artificial skin.
The invention has the following remarkable advantages:
(1) the existing products generally add the antibacterial substance to the dermis layer of the artificial skin, but the antibacterial substance fixed on the dermis layer disappears along with the degradation of collagen, thereby losing the antibacterial ability. The invention endows the artificial skin with the antibacterial function on the epidermal layer, and the silica gel film can not be degraded, so that the antibacterial substance fixed in the epidermal layer can exert the antibacterial effect for a long time, thereby reducing the infection of patients with large-area burn, improving the life saving rate and saving medical resources.
(2) The invention prepares the corium layer by crosslinking the denatured collagen and the fibrosis collagen, and leads the artificial skin to be gelated in the required time while ensuring the proper stability by controlling the crosslinking degree, thereby not only promoting the fiber cells and the blood vessel cells to enter the artificial skin in the early stage, ensuring the wound surface to form the dermal tissue more quickly, promoting the survival and the expansion of the transplanted skin, but also improving the mechanical strength of the artificial skin and preventing scar contracture. The artificial skin can be transplanted with the autologous epidermis at the same time, so that one-time treatment is realized, the defect that 2 operations are needed in the conventional artificial skin transplantation is overcome, the skin healing time can be greatly shortened, the life-saving rate of a patient suffering from large-area burn is improved, and the pain of the patient can be obviously reduced.
(3) The dermis layer of the artificial skin is prepared by physical crosslinking, so that the artificial skin has better safety compared with the existing artificial skin.
Drawings
FIG. 1 is a comparison of the artificial skin of the present invention (A) with a commercially available product 1 (B). As can be seen, the density of the dermal layer of the artificial skin of the present invention is high.
Detailed Description
In order to make the present invention more comprehensible, the technical solutions of the present invention are further described below with reference to specific embodiments, but the present invention is not limited thereto.
Examples
An artificial skin comprises epidermal layer and dermis layer, wherein the epidermal layer is antibacterial silica gel membrane with enhanced strength, and the dermis layer is three-dimensional porous structure composed of denatured collagen and fibrosis collagen. The preparation method comprises the following specific steps:
1) preparation of the skin layer: adding 10wt% of silicon nitride powder into the silicon rubber raw material, uniformly mixing the silicon rubber raw material and the silicon nitride powder, uniformly spreading the mixture into a film with the thickness of 200 mu m on the surface of a flat plate, and then attaching reticular polyester fibers to form the antibacterial silica gel film with enhanced strength;
2) preparation of dermis layer: dissolving the cattle collagen without the terminal peptides, and heating for 60 minutes at 90 ℃ to prepare denatured collagen; dissolving the collagen without the terminal peptide in phosphate buffer solution, heating for 60 minutes at 37 ℃, and filtering to obtain the fibrosis collagen; uniformly mixing the prepared denatured collagen and the prepared fibrosis collagen according to the weight ratio of 1:4, freeze-drying under the vacuum degree of 0.05Torr, and heating at 150 ℃ for 8 hours to prepare a dermis layer with the thickness of 2-3 mm;
3) preparing artificial skin:
uniformly coating a layer of fibrin glue on the reticular polyester fiber of the epidermal layer, and applying pressure to the prepared dermal layer to obtain the artificial skin with strength of 5 × 105dyne/cm2。
In order to promote the contact of the wound surface and the artificial skin and facilitate the discharge of the waste liquid of the wound, holes can be properly formed on the artificial skin. The cross section of the pore canal can be round or square, and the diameter is 1-5mm, preferably 2-3 mm.
TABLE 1 comparison of the Artificial skin of the invention with other commercially available products
1. Test for antibacterial Effect
Adding silicon nitride powder 10%, 5%, 1%, 0% into silicon rubber raw material, mixing to obtain silica gel film with different antibacterial substance contents, cutting the silica gel film into 5 cm × 5 cm test pieces (each 12 pieces with each concentration), sterilizing with ethanol, placing in a sterilized culture dish, and making into the final product with the weight ratio of 6.2 × 103~2.5×104Per cm2The same species were inoculated with 6 test pieces under the same conditions, 3 of which were directly used for measuring the bacterial count (N0). Adding 10mL of common broth culture medium into the remaining 3 pieces, culturing for 24 hours at 35 + -1 deg.C and relative humidity of above 90%, after 24 hours, recovering bacteria from each test piece, measuring bacteria number (Nt), determining antibacterial effect according to the ratio of Nt: N0, if the ratio is less than 10, indicating no antibacterial effect (indicated by "-"), the ratio is 10-100, indicating that certain antibacterial effect (indicated by "+"), the ratio is more than 100 and 1000, indicating better antibacterial effect (indicated by "+"), and the ratio is more than 1000, indicating that the antibacterial effect is good (indicated by "+ +"). The results are shown in Table 2.
TABLE 2 antibacterial Effect of the epidermal layer
2. Effect of denatured collagen content in dermis layer on usage of artificial skin
Mixing the denatured collagen and the fibrosis collagen at different ratios to obtain various dermal sponges with different denatured collagen contents, and cutting the sponges into 4cm pieces2Is placed in a circle which has been inoculated with 5 × 105cells/well 12-well plate of fibroblasts, 5% CO at 37. + -. 1 ℃ and 90% relative humidity or higher2Culturing in incubator for 4-6 days, taking out dermal sponge, fixing with formalin, and performing HE staining to examine fiber in various dermal sponges containing different denatured collagen contentThe degree of fibroblast ingrowth and the degree of maintenance of the morphological structure of the dermal sponge. Cells that only partially grew into the dermal sponge (less than half of the dermal sponge) are indicated by "+", cells that grew into most of the dermal sponge (more than half of the dermal sponge) are indicated by "+", and cells that grew into all of the dermal sponge are indicated by "+ + +". The degree of morphological structure maintenance of the eudermic sponge was estimated from the degree of degradation of the remaining eudermic sponge after the culture, and almost none of the remaining eudermic sponge was represented by "-", the remaining eudermic sponge was 1/3 or less and was "+", the remaining eudermic sponge was 1/3-1/2 or was 1/2 or more and was "+ +". The results are shown in Table 3.
TABLE 3 Effect of denatured collagen content in dermis on Artificial skin application
As can be seen from table 3, the use of denatured collagen greatly facilitates the entry of cells and has good degradability, thereby contributing to the rapid repair of burned skin.
3. The artificial skin and the autologous epidermis of the invention are transplanted simultaneously
1) Sampling of autologous epidermis
After 8-week-old SDC (Sprague Dawley) rats were shaved and disinfected, skin was collected on the back (area 2.0 cm. times.2.0 cm) using a drum-type skin collecting machine, and the collected skin was disinfected and washed and stored in physiological saline.
2) Full-thickness skin defect preparation
A2.0 cm × 2.0cm full-thickness skin defect is prepared from the skin area with the epidermis completely removed, and after complete hemostasis, the defect area is washed with physiological saline.
3) Artificial skin and autologous epidermal transplantation
Washing artificial skin of 2.0cm × 2.0cm prepared from different denatured collagen contents with physiological saline, attaching to the whole skin defect, laying the collected autologous epidermis on the artificial skin, and fixing the transplanted skin to the skin around the defect with 5-0 nylon suture. In order to ensure that the mother bed, the artificial skin and the autologous epidermis are fully sealed and moisturized, the wound is appropriately pressed and wrapped by dressings such as medical non-woven fabrics and the like after being sutured, and then the wound is fixed by an adhesive polyurethane film. Finally, 5mg/rat of amikacin sulfate and 10mg/rat of sodium sporinite were injected intramuscularly and subcutaneously, respectively, to prevent infection.
4) Periodic dressing changes to determine the presence of autologous epidermis
The dressing was changed every 3-4 days after surgery. The replacement is carried out according to the sequence of anesthesia, dressing removal, dressing replacement and dressing. After 14 days after the operation, the wound was removed after anesthesia and removal of the dressing to see whether the transplanted autologous epidermis was attached to the wound.
TABLE 4 Effect of denatured collagen content in dermis on Simultaneous transplantation of Artificial skin and autologous epidermal graft
The above description is only a preferred embodiment of the present invention, and all equivalent changes and modifications made in accordance with the claims of the present invention should be covered by the present invention.
Claims (10)
1. An artificial skin comprising an epidermal layer and a dermal layer, wherein: the epidermal layer is an antibacterial silica gel membrane with enhanced strength, and the dermal layer is a three-dimensional porous structure formed by denatured collagen and fibrosis collagen.
2. The artificial skin of claim 1, wherein: the antibacterial silica gel membrane with enhanced strength is prepared by attaching reticular polyester fiber, non-woven fabric, silk fibroin or polyurethane to one surface of the silica gel membrane close to the corium layer and adding antibacterial substances.
3. The artificial skin of claim 2, wherein: the antibacterial substance is silicon nitride, antibiotic, PHMB or silver-containing substance.
4. The artificial skin of claim 1, wherein: the dermis layer is prepared by mixing denatured collagen and fibrosis collagen, and then freeze-drying and physically crosslinking.
5. The artificial skin according to claim 1 or 4, wherein: the proportion of the denatured collagen in the dermis layer is 10-90 wt%.
6. The artificial skin according to claim 1 or 4, wherein: the raw material for preparing the denatured collagen and the fibrosis collagen is the collagen with the peptide removed.
7. The artificial skin according to claim 1 or 4, wherein: the porosity of the dermis layer is 80-98%, and the pore diameter is 50-250 μm.
8. The artificial skin of claim 1, wherein: the thickness of the epidermis layer is 3-500 μm, and the thickness of the dermis layer is 1-5 mm.
9. The artificial skin of claim 1, wherein: a plurality of pore canals which penetrate through the epidermis layer and the dermis layer are arranged in the artificial skin; the diameter of the pore canal is 1-5 mm.
10. The artificial skin according to claim 1, wherein the artificial skin has a strength of 2 × 105-10×105dyne/cm2。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010588871.5A CN111700713A (en) | 2020-06-24 | 2020-06-24 | Artificial skin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010588871.5A CN111700713A (en) | 2020-06-24 | 2020-06-24 | Artificial skin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111700713A true CN111700713A (en) | 2020-09-25 |
Family
ID=72543146
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010588871.5A Pending CN111700713A (en) | 2020-06-24 | 2020-06-24 | Artificial skin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111700713A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN113740491A (en) * | 2021-08-27 | 2021-12-03 | 无限极（中国）有限公司 | Simulated skin for sensory evaluation and preparation method thereof |
| CN114470338A (en) * | 2021-12-27 | 2022-05-13 | 湖北中部医疗科技有限公司 | Dermis, artificial skin and preparation method thereof |
Citations (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4060081A (en) * | 1975-07-15 | 1977-11-29 | Massachusetts Institute Of Technology | Multilayer membrane useful as synthetic skin |
| US4233360A (en) * | 1975-10-22 | 1980-11-11 | Collagen Corporation | Non-antigenic collagen and articles of manufacture |
| WO1989008466A1 (en) * | 1988-03-09 | 1989-09-21 | Terumo Kabushiki Kaisha | Medical material permitting cells to enter thereinto and artificial skin |
| US4882162A (en) * | 1987-06-26 | 1989-11-21 | Dow Corning Kabushiki Kaisha | Artificial skin |
| JPH0234165A (en) * | 1988-07-25 | 1990-02-05 | Terumo Corp | Artificial skin and manufacture |
| JPH0271748A (en) * | 1988-09-06 | 1990-03-12 | Terumo Corp | Artificial skin containing antibacterial agent and manufacture thereof |
| JPH03242142A (en) * | 1990-02-20 | 1991-10-29 | Terumo Corp | Artificial skin and production thereof |
| JPH04108444A (en) * | 1990-08-28 | 1992-04-09 | Gunze Ltd | Artificial skin |
| JPH04266763A (en) * | 1991-02-22 | 1992-09-22 | Terumo Corp | Artificial skin |
| US5263983A (en) * | 1988-03-09 | 1993-11-23 | Terumo Kabushiki Kaisha | Medical material and prosthetic skin in which cells can invade |
| US5350583A (en) * | 1988-03-09 | 1994-09-27 | Terumo Kabushiki Kaisha | Cell-penetrable medical material and artificial skin |
| JPH08196618A (en) * | 1995-01-23 | 1996-08-06 | Terumo Corp | Cell invasive collagen formulation, artificial skin and their manufacture |
| WO1997006837A1 (en) * | 1995-08-16 | 1997-02-27 | Integra Lifesciences Corporation | Perforated artificial skin grafts |
| EP1005873A1 (en) * | 1998-11-30 | 2000-06-07 | Isotis B.V. | Artificial skin |
| US20080113572A1 (en) * | 2006-11-10 | 2008-05-15 | Symatese | Device designed for regenerating the human dermis and process for producing said device |
| US20090012627A1 (en) * | 2007-07-03 | 2009-01-08 | Histogenics Corporation | Double-structured tissue implant and a method for preparation and use thereof |
| CN101716375A (en) * | 2009-11-20 | 2010-06-02 | 佘振定 | Artificial skin prepared from purely natural materials and having gradient hole structure and property |
| 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 |
| CN207545526U (en) * | 2017-01-12 | 2018-06-29 | 广东泰宝医疗器械技术研究院有限公司 | A kind of antibacterial artificial skin |
| CN109248337A (en) * | 2018-09-19 | 2019-01-22 | 深圳齐康医疗器械有限公司 | A kind of artificial dermis repair materials and preparation method thereof |
| JP2020006057A (en) * | 2018-07-12 | 2020-01-16 | 東洋インキＳｃホールディングス株式会社 | Biocompatible material, porous soft structure repair layer, porous biocompatible sheet, and artificial skin |
-
2020
- 2020-06-24 CN CN202010588871.5A patent/CN111700713A/en active Pending
Patent Citations (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4060081A (en) * | 1975-07-15 | 1977-11-29 | Massachusetts Institute Of Technology | Multilayer membrane useful as synthetic skin |
| US4233360A (en) * | 1975-10-22 | 1980-11-11 | Collagen Corporation | Non-antigenic collagen and articles of manufacture |
| US4882162A (en) * | 1987-06-26 | 1989-11-21 | Dow Corning Kabushiki Kaisha | Artificial skin |
| US5263983A (en) * | 1988-03-09 | 1993-11-23 | Terumo Kabushiki Kaisha | Medical material and prosthetic skin in which cells can invade |
| WO1989008466A1 (en) * | 1988-03-09 | 1989-09-21 | Terumo Kabushiki Kaisha | Medical material permitting cells to enter thereinto and artificial skin |
| US5350583A (en) * | 1988-03-09 | 1994-09-27 | Terumo Kabushiki Kaisha | Cell-penetrable medical material and artificial skin |
| JPH0234165A (en) * | 1988-07-25 | 1990-02-05 | Terumo Corp | Artificial skin and manufacture |
| JPH0271748A (en) * | 1988-09-06 | 1990-03-12 | Terumo Corp | Artificial skin containing antibacterial agent and manufacture thereof |
| JPH03242142A (en) * | 1990-02-20 | 1991-10-29 | Terumo Corp | Artificial skin and production thereof |
| JPH04108444A (en) * | 1990-08-28 | 1992-04-09 | Gunze Ltd | Artificial skin |
| JPH04266763A (en) * | 1991-02-22 | 1992-09-22 | Terumo Corp | Artificial skin |
| JPH08196618A (en) * | 1995-01-23 | 1996-08-06 | Terumo Corp | Cell invasive collagen formulation, artificial skin and their manufacture |
| WO1997006837A1 (en) * | 1995-08-16 | 1997-02-27 | Integra Lifesciences Corporation | Perforated artificial skin grafts |
| EP1005873A1 (en) * | 1998-11-30 | 2000-06-07 | Isotis B.V. | Artificial skin |
| US20080113572A1 (en) * | 2006-11-10 | 2008-05-15 | Symatese | Device designed for regenerating the human dermis and process for producing said device |
| US20090012627A1 (en) * | 2007-07-03 | 2009-01-08 | Histogenics Corporation | Double-structured tissue implant and a method for preparation and use thereof |
| CN101716375A (en) * | 2009-11-20 | 2010-06-02 | 佘振定 | Artificial skin prepared from purely natural materials and having gradient hole structure and property |
| 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 |
| CN207545526U (en) * | 2017-01-12 | 2018-06-29 | 广东泰宝医疗器械技术研究院有限公司 | A kind of antibacterial artificial skin |
| JP2020006057A (en) * | 2018-07-12 | 2020-01-16 | 東洋インキＳｃホールディングス株式会社 | Biocompatible material, porous soft structure repair layer, porous biocompatible sheet, and artificial skin |
| CN109248337A (en) * | 2018-09-19 | 2019-01-22 | 深圳齐康医疗器械有限公司 | A kind of artificial dermis repair materials and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| 孙维国等: "脱细胞异体真皮修复烧伤瘢痕的临床观察", 《中国美容医学》 * |
| 杨喜明等: "脱细胞异体真皮与自体表皮复合移植23例临床应用", 《陕西医学杂志》 * |
| 黄峻等: "异体脱细胞真皮基质与自体皮片复合移植治疗 增生性瘢痕", 《广东医学》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN113740491A (en) * | 2021-08-27 | 2021-12-03 | 无限极（中国）有限公司 | Simulated skin for sensory evaluation and preparation method thereof |
| CN113663134B (en) * | 2021-08-27 | 2023-02-28 | 苏州诺普再生医学有限公司 | Bionic skin stent and preparation method thereof |
| CN114470338A (en) * | 2021-12-27 | 2022-05-13 | 湖北中部医疗科技有限公司 | Dermis, artificial skin and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1259269B1 (en) | Agent for the treatment of wounds | |
| CN111700713A (en) | Artificial skin | |
| US8765468B2 (en) | Surgical device for skin therapy or testing | |
| US6383220B1 (en) | Artificial skin | |
| CN112807475B (en) | High-air-permeability degradable drug-loaded skin wound dressing and preparation method thereof | |
| JP4273450B2 (en) | Tissue regeneration substrate, transplant material, and production method thereof | |
| JP2002526204A (en) | Artificial dermis structure using neutralized chitosan sponge or neutralized chitosan / collagen mixed sponge | |
| CN111001041B (en) | Anti-inflammatory and antibacterial composite skin scaffold material and preparation method thereof | |
| CN110141681B (en) | Wound repair material for cell suspension transplantation and preparation method thereof | |
| EP0411124B1 (en) | Medical material permitting cells to enter thereinto and artificial skin | |
| Sheridan et al. | Alternative wound coverings | |
| KR100608192B1 (en) | A Method for Producing a Neutralized Chitosan Sponge for Wound Dressing and Scaffold, and the Chitosan Sponge produced by the same | |
| JPH05184661A (en) | Artificial skin | |
| CN115181226A (en) | Micromolecule silk fibroin-based hydrogel and preparation method and application thereof | |
| CN104940981B (en) | Biologically active external application dressing and preparation method thereof | |
| Kuroyanagi | Advances in wound dressings and cultured skin substitutes | |
| KR100644078B1 (en) | Dermal substitute consisting of amnion and biodegradable polymer, the preparation method and the use thereof | |
| JP2001212170A (en) | Wound cover material | |
| CN112891610A (en) | Pig-derived fibrin-electrostatic spinning nanofiber antibacterial hemostatic patch and preparation method thereof | |
| CN112516369A (en) | Bioactive glass composite material for wound care and application method thereof | |
| EP1005873B1 (en) | Artificial skin | |
| Kuroyanagi et al. | Cytotoxicity tests for antimicrobial agents using cultured skin substitutes fixed at interface of air and culture medium | |
| CN214805987U (en) | Acellular dermal composite dressing | |
| CN115887785B (en) | Antibacterial artificial skin and preparation method thereof | |
| CN1737129B (en) | Artificial skin transplant and its preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200925 |