CN106512090A - 3D-printing artificial skin and preparation method thereof - Google Patents
3D-printing artificial skin and preparation method thereof Download PDFInfo
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/60—Materials for use in artificial skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
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Abstract
The invention discloses 3D-printing artificial skin and a preparation method thereof. The 3D-printing artificial skin comprises a dermis layer and an epidermal layer which are printed by a 3D printer, wherein the dermis layer comprises collagen and anticoagulant, the epidermal layer comprises a silicone gel layer with holes, the silicone gel layer comprises silicone gel and a curing agent, and the diameter of each hole is 1-3 micrometers. The 3D-printing artificial skin is excellent in anticoagulant property, capable of reducing coagulation in an artificial skin stent, capable of keeping the activity of secretory cells and high in repairability.
Description
Technical field
The present invention relates to technical field of medical instruments, specially a kind of 3D printing artificial skin and preparation method thereof.
Background technology
Skin is the maximum organ of human body, with holding people's internal water, prevents excessively radiating, breathes freely and prevents bacterium from invading
The function of attacking.If being only that the shallow-layer or small area of skin is damaged, new skin can autologous be regenerated, but if being subject to seriously
Wound, skin cannot be repaired on one's own account, generally the superficial skin at other positions of body or artificial skin must be transplanted to wound
On.
Advanced artificial skin has epidermal area and skin corium mostly, after which is implanted into damage location, semi permeable epidermal area
Protection can be played, breathe freely and prevents bacteria attack etc. from acting on.And skin corium has three-dimensional porous rack structure, several weeks after surgery
Afterwards, as support is constantly degraded, fibroblast and capillary grow into three-dimensional structure, under the conditions of sufficient blood supply, grow into
Cell keep high vigor, cell to secret out of collagen, corium is rebuild.In the wound of larger area skin, need
When repairing under the auxiliary of artificial skin, if produce substantial amounts of hemoglutination, occur scar, make the skin corium of artificial skin with it is bad
Dead contact tissue, is unfavorable for that capillary is grown into support.
Therefore, new artificial skin does not need only have the skin corium and ventilative epidermal area of three-dimensional porous structure, and
And should also have certain anticoagulant property.
The content of the invention
Present disclosure is to provide a kind of 3D printing artificial skin and preparation method thereof, is lacked with solving existing technology
Fall into.
Technical scheme one is as follows：A kind of 3D printing artificial skin, including skin corium and epidermal area, the skin corium
Printed by 3D printer with epidermal area and formed, skin corium is made up of collagen and anticoagulant.
Preferably, the epidermal area is made up of the silicone gel that hole is distributed with, the silicone gel by silicone adhesive and
Curing agent is constituted, and the aperture in the hole is 1 μm ~ 3 μm, and the curing agent is platinum complex.
Preferably, the skin corium is three-dimensional porous structure, and the porosity of the three-dimensional porous structure is 80% ~ 90%, hole
Footpath is 200 μm ~ 300 μm.
Preferably, the silicone adhesive and curing agent mass ratio are 5:1~8:1.
Preferably, the anticoagulant is sodium citrate, sodium citrate, sodium oxalate and ethylenediamine tetra-acetic acid（EDTA）In
Two or more.
Preferably, the anticoagulant is the quality of sodium citrate and sodium citrate, the sodium citrate and sodium citrate
Than for 1:2.
Technical scheme two is as follows：A kind of preparation method of 3D printing artificial skin, comprises the steps：
S1：Prepare the acetum of 0.5mol/L：Acetic acid is diluted using deionized water, the acetic acid for obtaining 0.5mol/L is molten
Liquid.
S2：Prepare collagen and sodium citrate mixed gel：Collagen is added in 0.5mol/L acetums obtained in S1, then
Anticoagulant is added, collagen/anticoagulant mixed gel is obtained.
S3：Prepare the skin corium of three-dimensional porous structure：Collagen obtained in S2/anticoagulant mixed gel is added into 3D printing
In the hopper of machine, the three-dimensional data in the damaged skin region obtained according to CT scan sets the program of 3D printer, starts and prints
Machine, is obtained the skin corium with three-dimensional porous structure, then by skin corium freeze-dried solidify afterwards, the three-dimensional porous structure
Porosity is 80% ~ 90%, and aperture is 200 μm ~ 300 μm.
S4：One layer of silicone gel is coated in corium layer surface obtained in S3, silicone gel is by silicone adhesive curing agent group
Into the mass ratio of silicone adhesive and curing agent is 5:1~8:1, the curing agent is platinum complex.
S5：After silicone gel solidification, punched with laser-beam drilling machine, that is, obtained 3D printing artificial skin, the hole
Uniform in silicone gel film surface distributed, the size in aperture is 1 μm ~ 3 μm.
Preferably, the addition of collagen described in step S2 be add 4.9 in every 100ml 0.5mol/L acetums ~
6.9g collagens, the addition of the anticoagulant is addition 0.01 ~ 0.1g anticoagulations in every 100ml 0.5mol/L acetums
Agent.
Preferably, the anticoagulant is sodium citrate, sodium citrate, sodium oxalate and ethylenediamine tetra-acetic acid（EDTA）In
Two or more.
Preferably, the anticoagulant is the quality of sodium citrate and sodium citrate, the sodium citrate and sodium citrate
Than for 1:2.
Beneficial effects of the present invention are：
（1）Method is simple, and preparation time is short, required abundant raw material source, and cheap, low production cost, 3D printing are artificial
Skin is made up of skin corium and epidermal area, simulates human body skin structure completely；
（2）3D printing artificial skin has high porosity, the aperture size that suitable dermal cell grows into and good mechanical property
Can, promote cell growth, wound healing；
（3）3D printing artificial skin has excellent anticoagulant property, reduces the blood coagulation in artificial skin's support, keeps the work of secretory cell
Property, prosthetic is strong.
Specific embodiment
Embodiment one：
A kind of preparation method of 3D printing artificial skin, comprises the following steps：
S1:Prepare the acetum of 0.5mol/L：Acetic acid is diluted using deionized water, the acetic acid of 0.5mol/L is obtained
Solution；
S2:Prepare collagen and sodium citrate mixed gel：Take, then plus
Enter the anticoagulant that 0.1g is made up of sodium citrate and sodium citrate, obtain collagen/anti-coagulants mixed gel, the sodium citrate
Mass ratio with sodium citrate is 1:1；
S3:Collagen obtained in S2/sodium citrate mixed gel is added in the hopper of 3D printer, according to receiving that CT scan is obtained
The three-dimensional data of skin area is damaged, the program of 3D printer is set, starts printer, the corium with three-dimensional porous structure is obtained
Layer, the porosity of freeze-dried solidify afterwards, wherein three-dimensional porous structure is 85%, and aperture is at 250 μm；
S4:One layer of silicone gel is coated in corium layer surface obtained in S3, silicone gel is made up of silicone adhesive and curing agent,
The mass ratio of silicone adhesive and curing agent is 6:1；
S5：After silicone gel solidification, with laser-beam drilling machine so that silicone gel film surface distributed hole of uniform size, wherein
The size in hole is 2 μm, that is, obtain 3D printing artificial skin.
Embodiment two
S1:Prepare the acetum of 0.5mol/L：Acetic acid is diluted using deionized water, the acetic acid of 0.5mol/L is obtained
Solution；
S2:Prepare collagen and sodium citrate mixed gel：Take, then plus
Enter the anticoagulant that 0.1g is made up of sodium citrate, sodium citrate and EDTA, obtain collagen/anti-coagulants mixed gel, the lemon
The mass ratio of lemon acid sodium, sodium citrate and EDTA is 1:1:1；
S3:Collagen obtained in S2/sodium citrate mixed gel is added in the hopper of 3D printer, according to receiving that CT scan is obtained
The three-dimensional data of skin area is damaged, the program of 3D printer is set, starts printer, the corium with three-dimensional porous structure is obtained
Layer, the porosity of freeze-dried solidify afterwards, wherein three-dimensional porous structure is 85%, and aperture is at 250 μm；
S4:One layer of silicone gel is coated in corium layer surface obtained in S3, silicone gel is made up of silicone adhesive and curing agent,
The mass ratio of silicone adhesive and curing agent is 5:1；
S5：After silicone gel solidification, with laser-beam drilling machine so that silicone gel film surface distributed hole of uniform size, wherein
The size in hole is 2 μm, that is, obtain 3D printing artificial skin.
Embodiment three
S1:Prepare the acetum of 0.5mol/L：Acetic acid is diluted using deionized water, the acetic acid of 0.5mol/L is obtained
Solution；
S2:Prepare collagen and sodium citrate mixed gel：Take, then plus
Enter the anticoagulant that 0.1g is made up of sodium citrate, sodium citrate and sodium oxalate, obtain collagen/anti-coagulants mixed gel, it is described
The mass ratio of sodium citrate, sodium citrate and sodium oxalate is 1:1:1；
S3:Collagen obtained in S2/sodium citrate mixed gel is added in the hopper of 3D printer, according to receiving that CT scan is obtained
The three-dimensional data of skin area is damaged, the program of 3D printer is set, starts printer, the corium with three-dimensional porous structure is obtained
Layer, the porosity of freeze-dried solidify afterwards, wherein three-dimensional porous structure is 85%, and aperture is at 250 μm；
S4:One layer of silicone gel is coated in corium layer surface obtained in S3, silicone gel is made up of silicone adhesive and curing agent,
The mass ratio of silicone adhesive and curing agent is 8:1；
S5：After silicone gel solidification, with laser-beam drilling machine so that silicone gel film surface distributed hole of uniform size, wherein
The size in hole is 2 μm, that is, obtain 3D printing artificial skin.
Example IV
S1:Prepare the acetum of 0.5mol/L：Acetic acid is diluted using deionized water, the acetic acid of 0.5mol/L is obtained
Solution；
S2:Prepare collagen and sodium citrate mixed gel：Take, then plus
Enter the anticoagulant that 0.1g is made up of sodium citrate and sodium citrate, obtain collagen/anti-coagulants mixed gel, the sodium citrate
Mass ratio with sodium citrate is 1:2；
S3:Collagen obtained in S2/sodium citrate mixed gel is added in the hopper of 3D printer, according to receiving that CT scan is obtained
The three-dimensional data of skin area is damaged, the program of 3D printer is set, starts printer, the corium with three-dimensional porous structure is obtained
Layer, the porosity of freeze-dried solidify afterwards, wherein three-dimensional porous structure is 85%, and aperture is at 250 μm；
S4:One layer of silicone gel is coated in corium layer surface obtained in S3, silicone gel is made up of silicone adhesive and curing agent,
The mass ratio of silicone adhesive and curing agent is 8:1；
S5：After silicone gel solidification, with laser-beam drilling machine so that silicone gel film surface distributed hole of uniform size, wherein
The size in hole is 2 μm, that is, obtain 3D printing artificial skin.
Embodiment five
To verify whether 3D printing artificial skin of the present invention reaches expected invention effect, embodiment one to example IV is obtained
3D printing artificial skin carries out the experiment of prothrombin time, partial thromboplastin time and thrombin time,
Detection method：0.1g 3D printings artificial skin obtained in embodiment one to example IV is added in whole blood, and is positioned over 37
1h is shaken up at DEG C, then Jing 2500 leaves the heart 10 minutes, it is to be measured to take blood plasma, when fibrin ferment is detected with full-automatic blood coagulation analyzer
Between, partial thromboplastin time and thrombin time.As a result it is as shown in table 1 below：
1 anticoagulation function result of the test of table
As can be seen from the above table, the 3D printing artificial skin that prepared by the present invention has excellent anticoagulation function, and from embodiment 4
As can be seen that when anticoagulant is made up of sodium citrate and sodium citrate, and the mass ratio of sodium citrate and sodium citrate is 1:2
When, its anticoagulation function is best.
Embodiment six
Comparative example：For individually with collagen dressing.
Experimental group：For the 3D printing artificial skin that the method for embodiment 1～4 is prepared from.
3D printing artificial skin prepared by above-described embodiment 1～4 is carried out into wound reparative experiment, contrast experiment with comparative example
Group and repairing effect of the comparative example to the surface of a wound.Experimental result is as shown in table 2：
2 wound reparative experiment result of table
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Comparative example | |
| Wound healing time（d） | 7 | 6 | 7 | 5 | 12 |
| Healing state | Wound healing is complete | Wound healing is complete | Wound healing is complete | Wound healing is complete | Wound healing is complete |
As seen from the above table, prepared by embodiment 1 ~ 4 3D printing artificial skin and comparative example can to wound surface complete correction, but
It is that, compared with comparative example, the time needed for embodiment 1 ~ 4 is appreciably shorter, illustrates that the present invention is made by biological three-dimensional printing technology
The 3D printing artificial skin for obtaining has the effect for significantly promoting wound healing, and when anticoagulant is by sodium citrate and citric acid
Sodium is constituted, and the mass ratio of sodium citrate and sodium citrate is 1:When 2, which promotes the effect of wound healing most prominent.
Above only certain embodiments of the present invention is illustrated, but the protection content of the present invention is not only limited to the above
Embodiment, in the art of the present invention, the usual knowledge of a GPRS, it is possible to carry out in the range of its technology main idea
Diversified change.
Claims (10)
1. a kind of 3D printing artificial skin, including skin corium and epidermal area, the skin corium and epidermal area printed by 3D printer and
Into, it is characterised in that skin corium is made up of collagen and anticoagulant.
2. a kind of 3D printing artificial skin according to claim 1, it is characterised in that the epidermal area is by the silicone that hole is distributed with
Gel layer is constituted, and the silicone gel is made up of silicone adhesive and curing agent, and the aperture in the hole is 1 μm ~ 3 μm, the solidification
Agent is platinum complex.
3. a kind of 3D printing artificial skin according to claim 1, it is characterised in that the skin corium is three-dimensional porous structure,
The porosity of the three-dimensional porous structure is 80% ~ 90%, and aperture is 200 μm ~ 300 μm.
4. a kind of 3D printing artificial skin according to claim 2, it is characterised in that the silicone adhesive and curing agent mass ratio are
5:1~8:1。
5. a kind of 3D printing artificial skin according to claim 1, it is characterised in that the anticoagulant is sodium citrate, Chinese holly
Rafter acid sodium, sodium oxalate and ethylenediamine tetra-acetic acid（EDTA）In two or more.
6. a kind of 3D printing artificial skin according to claim 5, it is characterised in that the anticoagulant is sodium citrate and Chinese holly
The mass ratio of rafter acid sodium, the sodium citrate and sodium citrate is 1:2.
7. a kind of preparation method of 3D printing artificial skin a kind of as described in claim 1 ~ 5, it is characterised in that including walking as follows
Suddenly：
S1：Prepare the acetum of 0.5mol/L：Acetic acid is diluted using deionized water, the acetic acid for obtaining 0.5mol/L is molten
Liquid；
S2：Prepare collagen and sodium citrate mixed gel：Collagen is added in 0.5mol/L acetums obtained in S1, is added
Anticoagulant, obtains collagen/anticoagulant mixed gel；
S3：Prepare the skin corium of three-dimensional porous structure：Collagen obtained in S2/anticoagulant mixed gel is added into 3D printer
In hopper, the three-dimensional data in the damaged skin region obtained according to CT scan sets the program of 3D printer, starts printer,
The skin corium with three-dimensional porous structure is obtained, then by skin corium freeze-dried solidify afterwards, the hole of the three-dimensional porous structure
Gap rate is 80% ~ 90%, and aperture is 200 μm ~ 300 μm；
S4：One layer of silicone gel is coated in corium layer surface obtained in S3, silicone gel is made up of silicone adhesive curing agent, silicon
The mass ratio of ketone glue and curing agent is 5:1~8:1, the curing agent is platinum complex；
S5：After silicone gel solidification, punched with laser-beam drilling machine, that is, obtained 3D printing artificial skin, the hole is in silicon
Ketone gel film surface is evenly distributed, and the size in aperture is 1 μm ~ 3 μm.
8. a kind of preparation method of 3D printing artificial skin according to claim 7, it is characterised in that collagen described in step S2
Addition be that 4.9 ~ 6.9g collagens are added in every 100ml 0.5mol/L acetums, the addition of the anticoagulant is every
0.01 ~ 0.1g anticoagulants are added in 100ml 0.5mol/L acetums.
9. a kind of preparation method of 3D printing artificial skin according to claim 7, it is characterised in that the anticoagulant is lemon
Lemon acid sodium, sodium citrate, sodium oxalate and ethylenediamine tetra-acetic acid（EDTA）In two or more.
10. a kind of preparation method of 3D printing artificial skin according to claim 9, it is characterised in that the anticoagulant is
The mass ratio of sodium citrate and sodium citrate, the sodium citrate and sodium citrate is 1:2.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109330752A (en) * | 2018-10-22 | 2019-02-15 | 中国人民解放军陆军军医大学第附属医院 | 3D printing intravascular stent |
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