CN108392676A - A kind of biology 3D printing full custom skin and preparation method thereof - Google Patents
A kind of biology 3D printing full custom skin and preparation method thereof Download PDFInfo
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- CN108392676A CN108392676A CN201810463765.7A CN201810463765A CN108392676A CN 108392676 A CN108392676 A CN 108392676A CN 201810463765 A CN201810463765 A CN 201810463765A CN 108392676 A CN108392676 A CN 108392676A
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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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
- A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
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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
- A61L27/14—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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
- A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
- A61L27/3813—Epithelial cells, e.g. keratinocytes, urothelial cells
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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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
- A61L27/3895—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
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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
- A61L27/60—Materials for use in artificial skin
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y10/00—Processes of additive manufacturing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y50/00—Data acquisition or data processing for additive manufacturing
- B33Y50/02—Data acquisition or data processing for additive manufacturing for controlling or regulating additive manufacturing processes
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- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y70/00—Materials specially adapted for additive manufacturing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y80/00—Products made by additive manufacturing
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Abstract
The present invention relates to organization engineering skin technical field, specially a kind of biological 3D printing full custom skin and preparation method thereof, including two parts, a part are the extractive techniques of skin progenitor cell, a part is the biological 3D remodelings technology of skin.Skin progenitor cell extracts：Tissue acquisition and processing, tissue enzymolysis, primitive cell culture, secondary culture etc..Utilize biological 3D printer, using 3-D scanning modeling technique, it prints raw material and print specifications calculates, substrate printing, is layered printing, the method successively stacked, print the privileged site that can comply fully with human body, the full custom skin of specific three dimensional feature, it ensure that artificial skin is bonded with the complete of wound, improve transplanting success rate and curative effect.Meanwhile full custom skin can also be used for the research of vitro skin model, play a great role in tumor research, drug and cosmetics test etc..
Description
Technical field
A kind of biological 3D printing full custom skin of the present invention and preparation method thereof, belongs to organization engineering skin technical field.
Background technology
Skin plays irreplaceable as human body vitals in the normal operation that external environment, protection human body is isolated
Effect.The a variety of causes such as inflammation, burn, wound can all be damaged to our skin tape, to our healths and life band
Carry out grave danger.According to actual needs, there is the method for auto-skin grafting, but success rate is relatively low and skin-derived is limited
The always defect of this method is extremely restricted in large-area burns and the healing of especial patient.
With the development and progress of medical technology, there is artificial skin technology.The defect of auto-skin grafting is compensated for,
Only need obtained from autologous skin a small amount of Skin Cell can in vitro culture go out required skin histology, this is in skin patient
Great function has been played in treatment and the research of skin histology.With the further maturation of technology, it is already possible to which turning out has
There is the full thickness skin of same alike result with human skin, still, current artificial skin is mostly craft or plane printing, in life
It is all limited in production efficiency and therapeutic effect.
Invention content
The present invention has overcome the deficiencies of the prior art and provide a kind of biological 3D printing full custom skin and preparation method thereof,
The technology uses 3-D scanning modeling technique, layering printing, the method successively stacked to print human body specific position, specific thickness
The skin histology of degree, specific shape has accomplished the full custom type skin printed according to actual needs.
A kind of biological 3D printing full custom skin of the present invention and preparation method thereof, includes the steps that carrying out successively as follows：
3D is scanned and skin modeling, is scanned to human skin damaged part using spatial digitizer, obtains skin damage portion
The three-dimensional structure of position, then calculate wound with software and need each attribute of full custom skin transplanted, including：PDMS substrates are three-dimensional
Model and dermal composition model；Establish the skin model for meeting skin damage position three-dimensional structure so that full custom skin is complete
It is bonded wound, estimates out the quantity for needing stem cell；
Cell extraction extracts a small amount of human skin tissue, through over cleaning, sterilizes, weighs, shreds and obtain the good skin of preliminary treatment
Tissue, is added corresponding protease and clostridiopetidase A carries out tissue enzymolysis, obtain free skin cell tissue's liquid；It is obtained by filtration thin
Cytosol, centrifugation aggregation cell, then culture dish is seeded cells into, obtain primary Skin Cell；
Original cuiture takes a part of primary cell, addition ROCK inhibitor to be cultivated, through secondary culture after a period of time, obtained
To the epidermal stem cells of requirement；A part of primary cell is taken, ROCK inhibitor is not added and is cultivated, through after a period of time
Secondary culture turns out the corium stem cell of requirement；
3D layering printings, first pass through 3D printer and print PDMS basals；Collagen gel layer, glue are printed in PDMS substrates
Dermal cell layer is printed on former gel layer, prints collagen gel layer on dermal cell layer, epidermis is printed in collagen gel layer
Cellular layer prints collagen gel layer again on cuticular cellulose；
The number of plies and thickness of the dermal cell layer, collagen gel layer and cuticular cellulose carry out Modeling Calculation according to actual needs
It determines.
Skin histology culture and transplanting, by printed full custom cutaneous metastatic to culture dish, insulating box gas-liquid interface
Culture 2-10 days, waits for that skin histology tentatively merges, then is transplanted to skin damage position or carries out vitro skin model test.
The cell extraction, it is only necessary to it extracts a small amount of tissue, carries out cell separation, medicine irritation, secondary culture, i.e.,
Corium stem cell and the epidermal stem cells of sufficient amount can be obtained.
The epidermal stem cells and corium stem cell are saved in liquid nitrogen, in case printing uses；It will when needing to print
Cell is transferred in the raw material box of printer.
The dermal composition model includes cell and the gel original of the three-dimensional construction of skin, the composition of printable layer and needs
Material.
The print procedure of every layer of collagen gel is：One layer of crosslinking agent is first printed, prints one layer of collagen gel on it,
Crosslinking agent is printed again fixes this layer；The print procedure of cellular layer is：One layer of crosslinking agent is first printed, it is solidifying to print one layer of collagen on it
Glue prints one layer of cells layer on gel, then prints crosslinking agent and fix this layer.
The collagen gel material can also be other biological degradation material or with other biological degradation material
Mixture.
Full custom skin made of a kind of biology 3D printing full custom skin and preparation method thereof.
The purposes of full custom skin made of a kind of biology 3D printing full custom skin and preparation method thereof.
Compared with prior art, the beneficial effects of the present invention are：
Skin is divided into dermal cell layer, epidermal cell by a kind of preparation of full custom skin provided by the invention according to modeling
Layer, hydrogel cellular layer, are printed, the mode successively stacked prints the full custom constructed close to human skin by multilayer
Skin is the global function skin that can generate cuticula and hair.Full custom skin provided by the invention, can be used for various skins
Disease, such as psoriasis, acne, the skin repair of albinism patient.It can also be used for the skin repair of the patients such as burn, diabetes.
And full custom skin and wound the characteristics of fitting like a glove, it ensure that high success rate and better curative effect.
The present invention utilizes emerging 3D printing technique, and process modification is carried out on the basis of traditional 3D printing skin, passes through
Skin scanning modeling, printing raw material and print specifications calculate, substrate printing, layering printing, cultivate for use skin preparation process,
The privileged site that can comply fully with human body, the full custom skin of specific three dimensional feature are printed, ensure that artificial skin and wound
Complete fitting, improve transplanting success rate and curative effect.Meanwhile full custom skin can also be used for grinding for vitro skin model
Study carefully, plays a great role in skin disease, tumor research, drug screening and cosmetics test etc..
The printing of full custom skin of the present invention, skin histology are transplanted after culture, the skin group after culture
It knits the survival that ensure that cell health and so that there is certain bonding between cell, wound could be preferably cured after transplanting in this way
It closes, ensure that dermatoplastic success rate and better Wound healing effect, pushed the progress of medical technology.
Description of the drawings
Fig. 1 is that skin progenitor cell of the present invention extracts flow chart；
Fig. 2 is that skin 3D of the present invention remolds flow chart；
Fig. 3 is present invention printing skin multilayer composition figure
In figure, 1 is collagen gel layer；2 be PDMS substrates；3 be corium layer；4 be epidermal stem cells layer.
Specific implementation mode
With reference to specific embodiment, the present invention is described in further detail, but protection scope of the present invention is not
Be limited to these embodiments, it is every without departing substantially from the change of present inventive concept or equivalent substitute be included in protection scope of the present invention it
It is interior.
Embodiment 1
A kind of biological 3D printing full custom skin of the present invention and preparation method thereof, includes the steps that carrying out successively as follows：
3D is scanned and skin modeling, is scanned to human skin damaged part using spatial digitizer, obtains skin damage portion
The three-dimensional structure of position, then calculate wound with software and need each attribute of full custom skin transplanted, including：PDMS substrates are three-dimensional
Model and dermal composition model；Establish the skin model for meeting skin damage position three-dimensional structure so that full custom skin is complete
It is bonded wound, estimates out the quantity for needing stem cell；
Cell extraction extracts 0.1g human skin tissues, through over cleaning, sterilizes, weighs, shreds and obtain the good skin of preliminary treatment
Tissue, is added corresponding protease and clostridiopetidase A carries out tissue enzymolysis, obtain free skin cell tissue's liquid；It is obtained by filtration thin
Cytosol, centrifugation aggregation cell, then culture dish is seeded cells into, obtain primary Skin Cell；
Original cuiture takes a part of primary cell, and addition ROCK kinases inhibitors Y-27632 is cultivated, by one section
Time secondary culture obtains the epidermal stem cells of requirement；A part of primary cell is taken, ROCK inhibitor is not added and is trained
It supports, through secondary culture after a period of time, turns out the corium stem cell of requirement；
The tectonic model of PDMS substrates model and skin, is separately converted to the execution number of biological 3D printer by 3D layering printings
According to, and it is sent to printer.It refers to that the data of tectonic model are converted into printer head operating path and work to execute data
The data of state.
First according to PDMS substrate model datas, the three-dimensional PDMS mould similar with human body wound is processed by 3D printer
Type, the substrate as skin printing；One layer of collagen gel is printed in PDMS substrates, one layer of corium of printing is thin in collagen gel layer
Born of the same parents' layer, prints three layers of collagen gel layer on dermal cell layer, one layer of cuticular cellulose is printed in collagen gel layer, in epidermis
One layer of collagen gel layer is printed on cellular layer again；
Skin histology culture and transplanting, by printed full custom cutaneous metastatic to culture dish, insulating box gas-liquid interface culture
It 10, waits for that skin histology tentatively merges, then is transplanted to skin damage position or carries out vitro skin model test.
Embodiment 2
A kind of biological 3D printing full custom skin of the present invention and preparation method thereof, includes the steps that carrying out successively as follows：
3D is scanned and skin modeling, is scanned to human skin damaged part using spatial digitizer, obtains skin damage portion
The three-dimensional structure of position, then calculate wound with software and need each attribute of full custom skin transplanted, including：PDMS substrates are three-dimensional
Model and dermal composition model；Establish the skin model for meeting skin damage position three-dimensional structure so that full custom skin is complete
It is bonded wound, estimates out the quantity for needing stem cell；
Cell extraction extracts 0.2g human skin tissues, through over cleaning, sterilizes, weighs, shreds and obtain the good skin of preliminary treatment
Tissue, is added corresponding protease and clostridiopetidase A carries out tissue enzymolysis, obtain free skin cell tissue's liquid；It is obtained by filtration thin
Cytosol, centrifugation aggregation cell, then culture dish is seeded cells into, obtain primary Skin Cell；
Original cuiture takes a part of primary cell, and addition ROCK kinases inhibitors Y-27632 is cultivated, by one section
Time secondary culture obtains the epidermal stem cells of requirement；A part of primary cell is taken, ROCK inhibitor is not added and is trained
It supports, through secondary culture after a period of time, turns out the corium stem cell of requirement；
The tectonic model of PDMS substrates model and skin, is separately converted to the execution number of biological 3D printer by 3D layering printings
According to, and it is sent to printer.It refers to that the data of tectonic model are converted into printer head operating path and work to execute data
The data of state.
First according to PDMS substrate model datas, the three-dimensional PDMS mould similar with human body wound is processed by 3D printer
Type, the substrate as skin printing；One layer of collagen gel is printed in PDMS substrates, one layer of corium of printing is thin in collagen gel layer
Born of the same parents' layer, prints three layers of collagen gel layer on dermal cell layer, one layer of cuticular cellulose is printed in collagen gel layer, in epidermis
One layer of collagen gel layer is printed on cellular layer again；
Skin histology culture and transplanting, by printed full custom cutaneous metastatic to culture dish, insulating box gas-liquid interface culture 6
Day, wait for that skin histology tentatively merges, then be transplanted to skin damage position or carry out vitro skin model test.
Embodiment 3
A kind of biological 3D printing full custom skin of the present invention and preparation method thereof, includes the steps that carrying out successively as follows：
3D is scanned and skin modeling, is scanned to human skin damaged part using spatial digitizer, obtains skin damage portion
The three-dimensional structure of position, then calculate wound with software and need each attribute of full custom skin transplanted, including：PDMS substrates are three-dimensional
Model and dermal composition model；Establish the skin model for meeting skin damage position three-dimensional structure so that full custom skin is complete
It is bonded wound, estimates out the quantity for needing stem cell；
Cell extraction extracts 0.3g human skin tissues, through over cleaning, sterilizes, weighs, shreds and obtain the good skin of preliminary treatment
Tissue, is added corresponding protease and clostridiopetidase A carries out tissue enzymolysis, obtain free skin cell tissue's liquid；It is obtained by filtration thin
Cytosol, centrifugation aggregation cell, then culture dish is seeded cells into, obtain primary Skin Cell；
Original cuiture takes a part of primary cell, and addition ROCK kinases inhibitors Y-27632 is cultivated, by one section
Time secondary culture obtains the epidermal stem cells of requirement；A part of primary cell is taken, ROCK inhibitor is not added and is trained
It supports, through secondary culture after a period of time, turns out the corium stem cell of requirement；
The tectonic model of PDMS substrates model and skin, is separately converted to the execution number of biological 3D printer by 3D layering printings
According to, and it is sent to printer.It refers to that the data of tectonic model are converted into printer head operating path and work to execute data
The data of state.
First according to PDMS substrate model datas, the three-dimensional PDMS mould similar with human body wound is processed by 3D printer
Type, the substrate as skin printing；Two layers of collagen gel is printed in PDMS substrates, one layer of corium of printing is thin in collagen gel layer
Born of the same parents' layer, prints two layers of collagen gel layer on dermal cell layer, one layer of cuticular cellulose is printed in collagen gel layer, in epidermis
Two layers of collagen gel layer is printed on cellular layer again；
Skin histology culture and transplanting, by printed full custom cutaneous metastatic to culture dish, insulating box gas-liquid interface culture 2
Day, wait for that skin histology tentatively merges, then be transplanted to skin damage position or carry out vitro skin model test.
The cell extraction, it is only necessary to extract a small amount of tissue, the extracted amount can be 0.1g, 0.15g, 0.2g,
0.25g or 0.3g carries out cell separation, medicine irritation, secondary culture, you can obtain corium stem cell and the epidermal stem of sufficient amount
Cell.
The number of plies and thickness of the dermal cell layer, collagen gel layer and cuticular cellulose are modeled according to actual needs
It calculates and determines.
The epidermal stem cells and corium stem cell are saved in liquid nitrogen, in case printing uses；It will when needing to print
Cell is transferred in the raw material box of printer.
The dermal composition model includes cell and the gel original of the three-dimensional construction of skin, the composition of printable layer and needs
Material.
The print procedure of every layer of collagen gel is：One layer of crosslinking agent is first printed, prints one layer of collagen gel on it,
Crosslinking agent is printed again fixes this layer；The print procedure of cellular layer is：One layer of crosslinking agent is first printed, it is solidifying to print one layer of collagen on it
Glue prints one layer of cells layer on gel, then prints crosslinking agent and fix this layer.
The collagen gel material can also be other biological degradation material or with other biological degradation material
Mixture.
Full custom skin made of biology 3D printing full custom skin of the invention and preparation method thereof, by corium layer
It is formed with epidermal stem cells layer, using successively printing, the mode of multiple-level stack meets the structure composition of real human body skin, is
The global function skin of cuticula and hair can be generated.The number of plies of the dermal cell layer, collagen gel layer and cuticular cellulose
Modeling Calculation determination is carried out according to actual needs with thickness.
Full custom skin made of a kind of biology 3D printing full custom skin and preparation method thereof, can be used for various skins
Disease, such as psoriasis, acne, the skin repair of albinism patient.It can also be used for the skin repair of the patients such as burn, diabetes.
And full custom skin and wound the characteristics of fitting like a glove, it ensure that high success rate and better curative effect.It is described
Full custom skin, it can also be used to the external model for preparing human body privileged site skin, facilitate melanoma tumors and various skin diseases,
The researchs such as drug screening, cosmetics test.
It is thin to be divided into dermal cell layer, epidermis according to modeling by a kind of preparation of full custom skin provided by the invention for skin
Born of the same parents layer, hydrogel cellular layer, printed by multilayer, the mode successively stacked, print close to human skin construct it is complete calmly
Skin processed is the global function skin that can generate cuticula and hair.Full custom skin provided by the invention, can be used for various skins
Skin disease, such as psoriasis, acne, the skin repair of albinism patient.The skin that can also be used for the patients such as burn, diabetes is repaiied
It is multiple.And full custom skin and wound the characteristics of fitting like a glove, it ensure that high success rate and better curative effect.
Full custom skin provided by the invention, it can also be used to which the external model for preparing human body privileged site skin facilitates black
The researchs such as pigmented tumors and various skin diseases, drug screening, cosmetics test.
The printing of full custom skin ensure that dermatoplastic success rate and better Wound healing effect, push doctor
The progress for the treatment of technology.
The present invention is not limited by embodiment illustrated herein, and is to fit to and principles disclosed herein and novelty
The consistent widest range of feature.
Claims (9)
1. a kind of biology 3D printing full custom skin and preparation method thereof, which is characterized in that include the steps that carrying out successively as follows：
3D is scanned and skin modeling, is scanned to human skin damaged part using spatial digitizer, obtains skin damage portion
The three-dimensional structure of position, then calculate wound with software and need each attribute of full custom skin transplanted, including：PDMS substrates are three-dimensional
Model and dermal composition model；Establish the skin model for meeting skin damage position three-dimensional structure so that full custom skin is complete
It is bonded wound, estimates out the quantity for needing stem cell；
Cell extraction extracts 0.1-0.3g human skin tissues, through over cleaning, sterilizes, weighs, shreds that obtain preliminary treatment good
Skin histology, is added corresponding protease and clostridiopetidase A carries out tissue enzymolysis, obtains free skin cell tissue's liquid；It filters
To cell liquid, centrifugation aggregation cell, then culture dish is seeded cells into, obtains primary Skin Cell；
Original cuiture takes a part of primary cell, and addition ROCK inhibitor is cultivated, by secondary culture, required for obtaining
The epidermal stem cells of amount；A part of primary cell is taken, ROCK inhibitor is not added and is cultivated, by secondary culture, is turned out
The corium stem cell of requirement；
3D layering printings, first pass through 3D printer and print PDMS basals；Collagen gel layer, glue are printed in PDMS substrates
Dermal cell layer is printed on former gel layer, prints collagen gel layer on dermal cell layer, epidermis is printed in collagen gel layer
Cellular layer prints collagen gel layer again on cuticular cellulose；
Skin histology culture and transplanting, by printed full custom cutaneous metastatic to culture dish, insulating box gas-liquid interface culture
It 2-10 days, waits for that skin histology tentatively merges, then is transplanted to skin damage position or carries out vitro skin model test.
2. a kind of biological 3D printing full custom skin as described in claim 1 and preparation method thereof, which is characterized in that described thin
Born of the same parents extract, it is only necessary to extract a small amount of tissue, carry out cell separation, medicine irritation, secondary culture, you can obtain sufficient amount
Corium stem cell and epidermal stem cells.
3. a kind of biological 3D printing full custom skin as described in claim 1 and preparation method thereof, which is characterized in that the table
Skin stem cell and corium stem cell are saved in liquid nitrogen, in case printing uses；It needs that cell is transferred to printing when printing
In the raw material box of machine.
4. a kind of biological 3D printing full custom skin as described in claim 1 and preparation method thereof, which is characterized in that the skin
Skin tectonic model includes the cell and gel material of the three-dimensional construction of skin, the composition of printable layer and needs.
5. a kind of biological 3D printing full custom skin as described in claim 1 and preparation method thereof, which is characterized in that described true
Skin cell layer, the number of plies of collagen gel layer and cuticular cellulose and thickness carry out Modeling Calculation determination according to actual needs.
6. a kind of biological 3D printing full custom skin as described in claim 1 and preparation method thereof, which is characterized in that described every
Layer collagen gel print procedure be：One layer of crosslinking agent is first printed, prints one layer of collagen gel on it, then prints crosslinking agent and consolidates
This fixed layer；The print procedure of cellular layer is：One layer of crosslinking agent is first printed, one layer of collagen gel is printed on it, is beaten on gel
One layer of cells layer is printed, then prints crosslinking agent and fixes this layer.
7. a kind of biological 3D printing full custom skin as described in claim 1 and preparation method thereof, which is characterized in that the glue
Former gel rubber material can also be other biological degradation material or the mixture with other biological degradation material.
8. full custom made of a kind of biological 3D printing full custom skin as described in claim 1-7 is any and preparation method thereof
Skin.
9. full custom made of a kind of biological 3D printing full custom skin as described in claim 1-7 is any and preparation method thereof
The use of skin.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109115377A (en) * | 2018-09-04 | 2019-01-01 | 成都新柯力化工科技有限公司 | A kind of flexible pressure-sensitive thin-film material and preparation method for electronic skin |
| CN110841113A (en) * | 2019-11-27 | 2020-02-28 | 黑龙江紫泰科技有限公司 | Preparation method of tissue engineering skin |
| CN110960730A (en) * | 2019-12-23 | 2020-04-07 | 吉林大学 | 3D printed bionic rejection-resistant artificial skin and preparation method thereof |
| CN112206357A (en) * | 2020-09-25 | 2021-01-12 | 清华大学 | Tissue engineering skin biological ink, preparation method, regeneration method and system |
| CN113950339A (en) * | 2019-06-13 | 2022-01-18 | 塞林克公司 | 3D biological printing skin tissue model |
| CN117398523A (en) * | 2023-06-29 | 2024-01-16 | 太原理工大学 | Preparation method of full-layer tissue engineering skin with epidermal ridges |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104548214A (en) * | 2015-02-10 | 2015-04-29 | 广州赛莱拉干细胞科技股份有限公司 | Artificial skin and preparation method thereof |
| CN105056307A (en) * | 2015-08-18 | 2015-11-18 | 苏州磐升生物技术有限公司 | Artificial skin and preparation method thereof |
| WO2016091336A1 (en) * | 2014-12-12 | 2016-06-16 | Ecole Polytechnique Federale De Lausanne (Epfl) | A method for building a structure containing living cells |
| CN106110401A (en) * | 2016-06-30 | 2016-11-16 | 上海大学 | Micro-nano composite double layer dermal scaffold and preparation method thereof |
| CN106421931A (en) * | 2016-11-10 | 2017-02-22 | 广东泰宝医疗科技股份有限公司 | Skin repair material with biological activity and method for preparing skin repair material |
| US20170072111A1 (en) * | 2013-11-20 | 2017-03-16 | Dermagenesis Llc | Skin printing and auto-grafting |
-
2018
- 2018-05-15 CN CN201810463765.7A patent/CN108392676A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170072111A1 (en) * | 2013-11-20 | 2017-03-16 | Dermagenesis Llc | Skin printing and auto-grafting |
| WO2016091336A1 (en) * | 2014-12-12 | 2016-06-16 | Ecole Polytechnique Federale De Lausanne (Epfl) | A method for building a structure containing living cells |
| CN104548214A (en) * | 2015-02-10 | 2015-04-29 | 广州赛莱拉干细胞科技股份有限公司 | Artificial skin and preparation method thereof |
| CN105056307A (en) * | 2015-08-18 | 2015-11-18 | 苏州磐升生物技术有限公司 | Artificial skin and preparation method thereof |
| CN106110401A (en) * | 2016-06-30 | 2016-11-16 | 上海大学 | Micro-nano composite double layer dermal scaffold and preparation method thereof |
| CN106421931A (en) * | 2016-11-10 | 2017-02-22 | 广东泰宝医疗科技股份有限公司 | Skin repair material with biological activity and method for preparing skin repair material |
Non-Patent Citations (1)
| Title |
|---|
| VIVIAN LEE ET AL.: "Design and Fabrication of Human Skin by Three-Dimensional Bioprinting", 《TISSUE ENGINEERING: PART C》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109115377A (en) * | 2018-09-04 | 2019-01-01 | 成都新柯力化工科技有限公司 | A kind of flexible pressure-sensitive thin-film material and preparation method for electronic skin |
| CN113950339A (en) * | 2019-06-13 | 2022-01-18 | 塞林克公司 | 3D biological printing skin tissue model |
| CN110841113A (en) * | 2019-11-27 | 2020-02-28 | 黑龙江紫泰科技有限公司 | Preparation method of tissue engineering skin |
| CN110960730A (en) * | 2019-12-23 | 2020-04-07 | 吉林大学 | 3D printed bionic rejection-resistant artificial skin and preparation method thereof |
| CN110960730B (en) * | 2019-12-23 | 2021-10-26 | 吉林大学 | 3D printed bionic rejection-resistant artificial skin and preparation method thereof |
| CN112206357A (en) * | 2020-09-25 | 2021-01-12 | 清华大学 | Tissue engineering skin biological ink, preparation method, regeneration method and system |
| CN112206357B (en) * | 2020-09-25 | 2021-12-28 | 清华大学 | Tissue engineering skin regeneration system |
| CN117398523A (en) * | 2023-06-29 | 2024-01-16 | 太原理工大学 | Preparation method of full-layer tissue engineering skin with epidermal ridges |
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Application publication date: 20180814 |