CN106361463B - A kind of manufacturing process of liver organization model configuration - Google Patents
A kind of manufacturing process of liver organization model configuration Download PDFInfo
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- CN106361463B CN106361463B CN201510438007.6A CN201510438007A CN106361463B CN 106361463 B CN106361463 B CN 106361463B CN 201510438007 A CN201510438007 A CN 201510438007A CN 106361463 B CN106361463 B CN 106361463B
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Abstract
A kind of liver organization model configuration and its manufacturing process belong to organ manufacture, biomaterial and the field of medical instrument technology.The structure includes agent structure, arterial vascular system, venous vasculature, nervous system and biliary system.Vascular system, nervous system and part biliary system are distributed in dendroid inside agent structure.The liver organization model configuration that the present invention is prepared using the interior mold of mold under the upper mold of different-diameter, multi-step and simulation artery/vein, nerve and biliary system, it ensure that the organic arrangement of artery, vein, nerve and the biliary system of different trends in same structure body, closer to the real topography of human organ, and the various physiological functions of liver can be completed.This method is simple for production, at low cost.
Description
Technical field
The invention belongs to the artificial manufacturing technology fields of organism complicated tissue organ, relate to the use of cell, synthesis high score
Sub- material, cell matrix materials prepare the process of complex organization's artificial liver, organizational project technique different from the past.
Background technology
The it is proposed of organizational engineering is that the manufacture of artificial organ and organ specifies a way forward with culture.Especially
Be today organ transplantation technique it is more and more ripe and in the case that corresponding organ origin is more and more in short supply, development is artificial
Histoorgan manufactures just at the task of top priority to promote the well-being of mankind.
Although artificial organ organ transplant or a relatively jejune field, need long-term accumulation and exploration, and
It is related to other ethics morals problems, but has had been developed that the structures such as bone, cartilage, skin are relatively simple artificial at present
Tissue, and have been obtained for certain clinical application.The present invention, by constantly putting into practice, gropes on the basis of previous work
The manufacturing method for going out a set of new artificial liver makes complicated device pipe, such as liver, heart, kidney, breast, manufacture significantly forward
It steps and goes a step further.
Invention content
The object of the present invention is to provide a kind of liver organization model configuration and its manufacturing process, make it in function and structure
Natural animal body liver is simulated, new possibility is provided for fields such as organ manufacture, transplanting.
Technical scheme is as follows：
A kind of liver organization model configuration, it is characterised in that：The liver organization model configuration includes agent structure, artery
Vascular system, venous vasculature, nervous system and biliary system；
Arterial vascular system, venous vasculature and the nervous system is arranged inside agent structure, part bile duct
System is distributed in agent structure, and another part is distributed in outside agent structure；The agent structure is followed successively by from the inside to the outside containing blood
Hydrogel layer, the hydrogel layer of seed cell containing liver, the hydrogel layer and protective layer containing stem cell of pipe seed cell；
Branch's tubulose that the arterial vascular system and the hydrogel that venous vasculature is the seed cell containing blood vessel are constituted
Structure；The nervous system (103) is the branched fiber binding structure that the hydrogel containing neural seed cell is constituted, the Within Human Biliary Tract
System is the conduit containing bile duct epithelial cell；Biliary system is arranged at vascular system in agent structure.
The outer profile of agent structure of the present invention is in shape, spindle shape, spheroid form or the ellipsoid of animal body liver
Shape.The protective layer is synthesis high molecular material.
Hydrogel of the present invention is all made of the sodium alginate, active peptide, glue that mass percentage concentration is 0.1~20%
Original, heparin, chondroitin sulfate, hyaluronic acid, mucopolysaccharide, glycoprotein, matrigel, dextrose, chitosan, gelatin and fibrin
At least one of original solution.The liver seed cell be liver cell or stem cell and liver cell mixture or stem cell with
Growth factor mixture；Stem cell is at least one of fat stem cell, embryonic stem cell and induced multi-potent stem cell；It is described
Blood vessel seed cell be fat stem cell, mesenchymal stem cell, vascular endothelial cell, smooth muscle cell, fibroblast,
At least one of embryonic stem cell and induced multi-potent stem cell；It is described nerve seed cell be neuron or Schwann cell,
Or stem cell and growth factor mixture.The synthesis high molecular material is using polyethylene, polycaprolactone, polyurethane, poly- four
The compound of vinyl fluoride, polylactic acid, polyester and one or more of lactic acid and ethanol copolymer material.
A kind of preparation method of liver organization model configuration provided by the invention, it is characterised in that：This method includes as follows
Step：
1) particular manufacturing craft is prepared：The particular manufacturing craft is prepared using the method for machining or 3 D-printing, which includes
Lower mold, interior mold, simulation biliary system mold and upper mold；The interior mold includes simulation arterial vascular system internal model
The interior mold of mold and simulated nervous system in tool, simulation venous vasculature；
2) three interior molds for simulating artery, vein and nervous system are inserted by three holes at the top of first order upper mold
And fix, it is then positioned over together on the first order step of lower mold fixed；Simulation biliary system mold is passed through into lower mold
On hole fix；The hydrogel of the seed cell containing blood vessel is filled into the gap between interior mold and first order upper mold later
In, and so that the hydrogel of the seed cell containing blood vessel be crosslinked using crosslinking agent, remove first order upper mold, is formed stable containing blood vessel
The hydrogel layer of seed cell；
3) it is placed on the second level step of lower mold and is fixed using the diameter second level upper mold bigger than the first order, will contained
The hydrogel of liver seed cell is filled into the gap between the hydrogel layer of the seed cell containing blood vessel and second level upper mold,
And so that the hydrogel of the seed cell containing liver is crosslinked using crosslinking agent, second level upper mold is removed, stable kind containing liver is formed
Daughter cell hydrogel layer；
4) according to the method for step 3), lower mold is placed on using the diameter third level upper mold bigger than second level upper mold
Third level step on it is fixed, the hydrogel containing stem cell is filled into liver seed cell hydrogel layer and third level upper mold
Between gap in, and so that the hydrogel containing stem cell is crosslinked using crosslinking agent, obtain the hydrogel layer containing stem cell；
5) mold and lower mold in removal divide in simulating artery and simulating the gap that mold leaves in venous vasculature
Other Perfused vessel endothelial cell forms arterial vascular system and simulation venous vasculature, and mold stays in simulated nervous system
Under gap in Schwann cell suspension is perfused, form branch nervous system；
6) the part biliary system by exposed outside agent structure is wrapped up with one layer of hydrogel containing liver cell, and using friendship
Connection agent makes celliferous hydrogel be crosslinked；
7) synthesis high molecular material is dissolved in and the synthesis high score that mass percentage concentration is 5%~30% is made in organic solvent
Sub- solution, is placed in spray bottle, laminated at high molecular material in the agent structure surface even application one of forming, is then placed in
It is extracted in PBS solution, finally obtains stable liver organization model configuration.
In the method for the present invention, the upper mold, lower mold simulate mold in arterial vascular system, simulation vein blood vessel
Mold in system, in simulated nervous system in mold and simulation biliary system mold using metal or synthesis high molecular material；Institute
It states metal and uses aluminium alloy, brass or stainless steel material；High molecular material is synthesized using polytetrafluoroethylene (PTFE), PBS plastics, photosensitive tree
Fat, rubber, acrylonitrile-butadiene-styrene copolymer plastics, polystyrene plastics, poly methyl methacrylate plastic, poly- first
Aldehyde plastics, vinyon, polyvinyl chloride, Maranyl, polycarbonate plastic, epoxy resin, gather in oneself polypropylene plastics
Ester, polyurethane or silicone plasties.
Compared with prior art, the present invention having the advantage that and the technique effect of high-lighting：1. the liver organization of the present invention
Model configuration has artery, vein, nerve and bile duct tissue's network, all more complicated than previous any artificial organs, closer to human body
The real topography of organ, and the various physiological functions of liver can be completed.2. the manufacturing process of the present invention ensure that different trends
The organic arrangement of artery, vein, nerve and biliary system in same structure body.3. this method is simple for production, at low cost.
Description of the drawings
Fig. 1 is liver organization model configuration schematic diagram.
Fig. 2 is the mold structure diagram for preparing liver organization model configuration.
In figure：101- arterial vascular systems；102- venous vasculatures；103- nervous systems；104- protective layers；105- contains
The hydrogel layer of stem cell；The 106- hydrogel layers of seed cell containing liver；The hydrogel layer of 107- seed cells containing blood vessel；108-
Biliary system.
Mold under 201-；202a- simulates mold in arterial vascular system；202b- simulates mold in venous vasculature；
Mold in 202c- simulated nervous systems；203 first order upper molds；The second level 204- upper mold；205- is simulated in biliary system
Mold.
Specific implementation mode
Following further describes the present invention with reference to the drawings.
As shown in Figure 1, a kind of liver organization model configuration provided by the invention includes agent structure, arterial vascular system
101, venous vasculature 102, nervous system 103 and biliary system 108；The arterial vascular system 101, venous blood piping
System 102 and nervous system 103 are arranged inside agent structure, and part biliary system 108 is distributed in agent structure, another portion
It is distributed in outside agent structure；The agent structure outer profile is in the shape of animal body liver, spindle shape, spheroid form or ellipse
Spheroid form.
The agent structure is followed successively by hydrogel layer 107, the seed cell containing liver of the seed cell containing blood vessel from the inside to the outside
Hydrogel layer 106, the hydrogel layer 105 containing stem cell and protective layer 104；The arterial vascular system and venous vasculature
The branch's tubular structure constituted for the hydrogel of the seed cell containing blood vessel；The nervous system 103 is containing neural seed cell
The branched fiber binding structure that hydrogel is constituted, the biliary system are the conduit containing bile duct epithelial cell；Biliary system and blood vessel
System interval is arranged in agent structure.
The hydrogel be all made of mass percentage concentration be 0.1~20% sodium alginate, active peptide, collagen, heparin,
In chondroitin sulfate, hyaluronic acid, mucopolysaccharide, glycoprotein, matrigel, dextrose, chitosan, gelatin and fibrinogen solution
At least one.
The liver seed cell is that liver cell or stem cell and liver cell mixture or stem cell and growth factor are mixed
Close object；Stem cell is at least one of fat stem cell, embryonic stem cell and induced multi-potent stem cell；The blood vessel kind is careful
Born of the same parents are fat stem cell, mesenchymal stem cell, vascular endothelial cell, smooth muscle cell, fibroblast, embryonic stem cell
At least one of with induced multi-potent stem cell；The nerve seed cell be neuron or Schwann cell or stem cell with
Growth factor mixture.
The protective layer 104 is synthesis high molecular material, and synthesis high molecular material uses polyethylene, polycaprolactone, gathers
The compound of urethane, polytetrafluoroethylene (PTFE), polylactic acid, polyester and one or more of lactic acid and ethanol copolymer material.
A kind of preparation method of liver organization model configuration provided by the invention, this method comprises the following steps：
1) particular manufacturing craft is prepared：The particular manufacturing craft is prepared using the method for machining or 3 D-printing, which includes
Lower mold 201, interior mold, simulation biliary system mold and upper mold；The interior mold includes in simulation arterial vascular system
The interior mold of mold and simulated nervous system in mold, simulation venous vasculature；Upper mold, lower mold, interior mold and external mold
Metal or synthesis high molecular material can be used in the material of tool, such as aluminium alloy, brass, stainless steel, polytetrafluoroethylene (PTFE), acrylic nitrile-butadiene
Diene-styrene copolymer (ABS) plastics, photosensitive resin, rubber, polystyrene (PS) plastics, polymethyl methacrylate
(PMMA) plastics (organic glass), polyformaldehyde (POM) plastics, polypropylene (PP) plastics, polyethylene (PE) plastics, polyvinyl chloride
(PVC), polyamide (PA) plastics (nylon), polycaprolactone (PCL), polyurethane (PU), makrolon (PC) plastics, epoxy resin
(EP) or silicone plasties (IS).
Lower mould inside is ladder-like, the hypothallus that the series of step can make as needed that becomes larger successively from the inside to the outside
Depending on number.The material of lower mold is that hard synthesizes high molecular material, (by taking level Four step as an example) as shown in Figure 2.
The upper mold of different-diameter is corresponding with the step of same diameter in lower mold.The shell of the upper mold of different-diameter
Thickness is corresponding with step widths at different levels in lower mold.
2) three interior molds 202 of artery, vein and nervous system will be simulated by three at the top of first order upper mold 203
Hole is inserted and fixed, and is then positioned over together on the first order step of lower mold 201 fixed；Biliary system mold will be simulated
205 pass through the hole on lower mold 201 to fix；The hydrogel of the seed cell containing blood vessel is filled into interior mold 202 and later
In gap between level-one upper mold 203, and so that the hydrogel of the seed cell containing blood vessel is crosslinked using crosslinking agent, removes the first order
Upper mold 203 forms the hydrogel layer 107 of the stable seed cell containing blood vessel；
3) it is placed on the second level step of lower mold 201 using the diameter second level upper mold 204 bigger than the first order solid
It is fixed, the hydrogel of the seed cell containing liver is filled into the hydrogel layer 107 and second level upper mold 204 of the seed cell containing blood vessel
Between gap in, and so that the hydrogel of the seed cell containing liver be crosslinked using crosslinking agent, removal second level upper mold 204, shape
At the stable hydrogel layer of seed cell containing liver 106；
4) according to the method for step 3), lower mold is placed on using the diameter third level upper mold bigger than second level upper mold
It is fixed on 201 third level step, the hydrogel containing stem cell is filled on liver seed cell hydrogel layer and the third level
In gap between mold, and so that the hydrogel containing stem cell is crosslinked using crosslinking agent, obtains the hydrogel layer containing stem cell；
5) mold and lower mold in removal divide in simulating artery and simulating the gap that mold leaves in venous vasculature
Other Perfused vessel endothelial cell forms arterial vascular system and simulation venous vasculature, and mold stays in simulated nervous system
Under gap in Schwann cell suspension is perfused, form branch nervous system；
6) the part biliary system by exposed outside agent structure is wrapped up with one layer of hydrogel containing liver cell, and using friendship
Connection agent makes celliferous hydrogel be crosslinked；
7) synthesis high molecular material is dissolved in and the synthesis high score that mass percentage concentration is 5%~30% is made in organic solvent
Sub- solution, is placed in spray bottle, laminated at high molecular material in the agent structure surface even application one of forming, is then placed in
It is extracted in PBS solution, finally obtains stable liver organization model configuration.
Several specific embodiments are enumerated below, to further understand the present invention.
Embodiment 1
1) polytetrafluoroethylene (PTFE) system standby upper mold containing two-stage step in a manner of mach is used, is prepared with polyurethane and contains one
The simulation arterial vascular system of grade branch, the interior mold for simulating venous vasculature and simulated nervous system, are prepared with polyethylene
Mold in the simulation biliary system of the branch containing level-one with micropore；Prepare 1% fibrinogen solution, will simulation artery, vein,
Nerve and four interior molds of biliary system are inserted by the hole in three holes and lower mold at the top of first order upper mold solid respectively
It is fixed, it is then fixed on the first order step of lower mold together.On interior mold and the first order have between injection fibrinogen with
The mixture of vascular endothelial cell, cell density are 1 × 107Then a/mL is added thrombin solution (20IU/mL) and is soaked into
Shape object polymerize for 2 minutes, removes first order upper mold, forms the stable hydrogel layer containing vascular endothelial cell；
2) it is sleeved on the second level step of base mould using the diameter second level upper mold bigger than the first order.By fiber egg
(cell density is 1 × 10 to white original/liver cell mixture5A/mL), it is filled into the hydrogel layer containing vascular endothelial cell and
In gap between two level upper mold, thrombin solution (20IU/mL), which is then added, makes fiber egg in the hydrogel containing liver cell
White former polymerization, removes upper mold, forms the stable hydrogel layer containing liver cell；
3) it is sleeved on the third level step of base mould using the diameter third level upper mold bigger than the second level.By fiber egg
(cell density is 1 × 10 to white original/fat stem cell mixture4A/mL), it is filled into hydrogel layer and third containing liver cell
In gap between grade upper mold, thrombin solution (20IU/mL), which is then added, makes fibrinogen in hydrogel containing liver cell
Polymerization removes upper mold, forms the hydrogel layer of stable fatty stem cell；
4) the interior mold and lower die of removal simulation arterial vascular system, simulation venous vasculature and simulated nervous system
Tool distinguishes Perfused vessel endothelial cell in simulating artery and simulating the gap that mold leaves in venous vasculature, is formed and moved
Arteries and veins vascular system is with simulation venous vasculature, and perfusion Schwann cell is outstanding in the gap that mold leaves in simulated nervous system
Supernatant liquid forms branch's nervous system；
5) the part biliary system by exposed outside agent structure is wrapped up with one layer of hydrogel containing liver cell, and using friendship
Connection agent makes celliferous hydrogel be crosslinked；
6) by synthesize macromolecule polyurethane be dissolved in be made in organic solvent mass percentage concentration be 5% synthesis macromolecule it is molten
Liquid is placed in spray bottle, in the one strata urethane of agent structure surface even application of forming, is then placed in PBS solution and is extracted
It takes, finally obtains stable liver organization model configuration.
Embodiment 2：
1) it is lower mold that raw material prepares the step containing three-level in a manner of 3D printing, upper mold and interior mold with ABS, with poly-
Ethylene prepares the interior mold of the branch containing two level；
2) 1% sodium alginate soln is prepared, by the three interior molds and an external mold of simulated blood vessel, nerve and biliary system
Tool is inserted and fixed by three holes of die top in the first order, is then positioned over together on the first order step of lower mold solid
It is fixed, and the branch of interior mold is inserted among the array hole of lower mold and is fixed.It injects and contains between interior mold and first order upper mold
The sodium alginate endothelial growth factor (EGF10ng/mL) of 1% taxol/fat stem cell mixture (cell density 1
×103A/mL), the calcium chloride that w/v is 1%, which is then added, makes sodium alginate cross-linking for 2 minutes, removes first order upper mold
Tool, forms the stable hydrogel layer containing endothelial growth factor/fat stem cell；
3) it is sleeved on the second level step of lower mold using the diameter second level upper mold bigger than the first order.By alginic acid
(cell density is 1 × 10 to sodium/hepatocyte growth factor (HGF0.5ng/mL)/fat stem cell mixture4A/mL) it is filled into
In gap between the hydrogel layer and second level upper mold of fatty stem cell, the chlorine that w/v is 1% is then added
Changing calcium makes sodium alginate cross-linking for 2 minutes, removes upper mold, forms the stable water containing hepatocyte growth factor/fat stem cell
Gel layer；
4) it is sleeved on the third level step of lower mold using the diameter third level upper mold bigger than the second level.By alginic acid
Sodium/fat stem cell mixture is filled into hydrogel layer and third level upper mold containing hepatocyte growth factor/fat stem cell
Between gap in, the calcium chloride that w/v is 1%, which is then added, makes sodium alginate cross-linking for 2 minutes, removes upper mold, shape
At the hydrogel layer of stable fatty stem cell；
6) upper and lower, middle mold is removed, perfusion Schwann cell suspends in the gap that mold leaves in simulated nervous system
Liquid forms branch's nervous system；
7) it is equipped with PLGA/ tetraethylene glycols (Tetraglycol) solution of a concentration of 10% (W/V), is added 1% (W/W's)
Taxol in spray injection bottle, in one layer of PLGA of artificial liver surface even application of forming, is then placed in PBS solution and extracts
It takes, obtains the liver organization model configuration of final stabilization.
Embodiment 3：
1) it is the raw material standby upper mold containing two-stage step, bed die in a manner of three-dimensional (3D) printing to use degradable metal magnesium
Tool, interior mold and outer mold；0.1% collagen solution is prepared, four internal models of artery, vein, nerve and biliary system will be simulated
Tool is fixed by the hole on lower mold.Collagen solution, stem cell and endothelium are injected between interior mold and first order upper mold
Porcine HGF (EGF0.5ng/mL) mixture, wherein stem cell density are 1 × 103A/mL, is then added 0.01M
Sodium hydroxide solution make within 2 minutes collagen polymerization forming, remove first order upper mold, formed it is stable containing stem cell with it is interior
The hydrogel layer of chrotoplast；
2) it is sleeved on the second level step of base mould using the diameter second level upper mold bigger than the first order.By fiber egg
(cell density is 1 × 10 to white original/stem cell mixture3A/mL), hepatocyte growth factor (HGF0.5ng/ is added
ML), human blood platelets derived growth factor (BB or PDGF-BB 50ng/mL), transforminggrowthfactor-β1 (1 10ng/mL of TGF β) and
Basic fibroblast growth factor (b-FGF 205ng/mL), is filled into the hydrogel layer containing stem cell and endothelial cell
In gap between the upper mold of the second level, thrombin solution (20IU/mL), which is then added, makes the fiber in cellular matrix solution
Fibrinogen polymerization removes upper mold and interior mold, is formed and stablizes the hydrogel layer containing stem cell and growth factor；
3) upper and lower, middle mold is removed, perfusion Schwann cell suspends in the gap that mold leaves in simulated nervous system
Liquid forms branch's nervous system；
4) it is equipped with PCL/ tetraethylene glycols (Tetraglycol) solution of a concentration of 20% (W/V), the liver of 1% (W/W) is added
Element in spray injection bottle, in one layer of PCL of artificial liver surface even application of forming, is then placed in PBS solution and extracts, obtain
To the liver organization model configuration of final stabilization.
Claims (6)
1. a kind of manufacturing process of liver organization model configuration, it is characterised in that：The liver organization model configuration includes main body
Structure, arterial vascular system (101), venous vasculature (102), nervous system (103) and biliary system (108)；
Arterial vascular system (101), venous vasculature (102) and the nervous system (103) is arranged in agent structure
Portion, part biliary system (108) are distributed in agent structure, and another part is distributed in outside agent structure；The agent structure from
In to be followed successively by the hydrogel layer (107) of the seed cell containing blood vessel, the hydrogel layer of seed cell containing liver (106) outside, containing dry thin
The hydrogel layer (105) and protective layer (104) of born of the same parents；
Branch's tubular structure that the arterial vascular system and the hydrogel that venous vasculature is the seed cell containing blood vessel are constituted；
The nervous system (103) is the branched fiber binding structure that the hydrogel containing neural seed cell is constituted, and the biliary system is
Conduit containing bile duct epithelial cell；Biliary system is arranged at vascular system in agent structure, inside agent structure, point
The arterial vascular system (101) of branch tubular structure, the venous vasculature (102) of branch's tubular structure and branched fiber binding
The nervous system (103) of structure is staggeredly arranged with biliary system inversion；
Described method includes following steps：
1) particular manufacturing craft is prepared：The particular manufacturing craft is prepared using the method for machining or 3 D-printing, which includes lower die
Have (201), interior mold, simulation biliary system mold and upper mold；The interior mold includes simulation arterial vascular system internal model
The interior mold of mold and simulated nervous system in tool, simulation venous vasculature；
2) three interior molds (202) of artery, vein and nervous system will be simulated by three at the top of first order upper mold (203)
Hole is inserted and fixed, and is then positioned over together on the first order step of lower mold (201) fixed；Biliary system mold will be simulated
(205) hole on lower mold (201) is passed through to fix；The hydrogel of the seed cell containing blood vessel is filled into interior mold later
(202) in the gap between first order upper mold (203), and the hydrogel of the seed cell containing blood vessel is made to hand over using crosslinking agent
Connection, removal first order upper mold (203), forms the hydrogel layer (107) of the stable seed cell containing blood vessel；
3) second level upper mold (204) for using diameter bigger than the first order is placed on the second level step of lower mold (201) solid
It is fixed, the hydrogel of the seed cell containing liver is filled into the hydrogel layer (107) and second level upper mold of the seed cell containing blood vessel
(204) in the gap between, and so that the hydrogel of the seed cell containing liver is crosslinked using crosslinking agent, remove second level upper mold
(204), the stable hydrogel layer of seed cell containing liver (106) is formed；
4) according to the method for step 3), lower mold is placed on using the diameter third level upper mold bigger than second level upper mold
(201) fixed on third level step, the hydrogel containing stem cell is filled into liver seed cell hydrogel layer and the third level
In gap between upper mold, and so that the hydrogel containing stem cell is crosslinked using crosslinking agent, obtains the hydrogel layer containing stem cell；
5) mold and lower mold in removing fill respectively in simulating artery and simulating the gap that mold leaves in venous vasculature
Blood vessel seed cell is noted, arterial vascular system and venous vasculature, the gap that mold leaves in simulated nervous system are formed
The neural seed cell suspension of middle perfusion, forms branch's nervous system；
6) the part biliary system by exposed outside agent structure is wrapped up with one layer of hydrogel containing liver cell, and uses crosslinking agent
Celliferous hydrogel is set to be crosslinked；
7) by synthesize high molecular material be dissolved in be made in organic solvent mass percentage concentration be 5%~30% synthesis macromolecule it is molten
Liquid is placed in spray bottle, laminated at high molecular material in the agent structure surface even application one of forming, is then placed in PBS
It is extracted in solution, finally obtains stable liver organization model configuration.
2. a kind of manufacturing process of liver organization model configuration as described in claim 1, it is characterised in that：The agent structure
Outer profile is in shape, spindle shape, spheroid form or the ellipsoid shape of animal body liver.
3. a kind of manufacturing process of liver organization model configuration as described in claim 1, it is characterised in that：The protective layer
(104) it is synthesis high molecular material, the synthesis high molecular material is using polyethylene, polycaprolactone, polyurethane, polytetrafluoroethyl-ne
The compound of alkene, polylactic acid, polyester and one or more of lactic acid and ethanol copolymer material.
4. a kind of manufacturing process of liver organization model configuration as described in claim 1, it is characterised in that：The hydrogel
Be all made of mass percentage concentration be 0.1~20% sodium alginate, active peptide, collagen, heparin, chondroitin sulfate, hyaluronic acid,
At least one of mucopolysaccharide, glycoprotein, matrigel, dextrose, chitosan, gelatin and fibrinogen solution.
5. a kind of manufacturing process of liver organization model configuration as described in claim 1, it is characterised in that：The liver seed
Cell is liver cell or stem cell and liver cell mixture or stem cell and growth factor mixture；Stem cell is that fat is dry thin
At least one of born of the same parents, embryonic stem cell and induced multi-potent stem cell；The blood vessel seed cell is between fat stem cell, marrow
In mesenchymal stem cells, vascular endothelial cell, smooth muscle cell, fibroblast, embryonic stem cell and induced multi-potent stem cell
It is at least one；The nerve seed cell is neuron or Schwann cell or stem cell and growth factor mixture.
6. the manufacturing process of the liver organization model configuration as described in claim 1-5 any claims, it is characterised in that：Institute
It states upper mold, lower mold (201), simulate mold (202a) in arterial vascular system, mold in simulation venous vasculature
In (202b), simulated nervous system mold (202c) and simulation biliary system in mold (205) using metal or synthesis macromolecule
Material；The metal uses aluminium alloy, brass or stainless steel material；The synthesis high molecular material of above-mentioned mold uses polytetrafluoroethyl-ne
Alkene, PBS plastics, photosensitive resin, rubber, acrylonitrile-butadiene-styrene copolymer plastics, polystyrene plastics, poly- methyl-prop
E pioic acid methyl ester plastics, acetal plastic, polypropylene plastics, vinyon, polyvinyl chloride, Maranyl, makrolon modeling
Material, epoxy resin, polycaprolactone, polyurethane or silicone plasties.
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| CN110403731B (en) * | 2019-07-30 | 2021-09-10 | 中国人民解放军陆军军医大学第一附属医院 | Tissue engineering bionic liver lobe structure based on living cell 3D printing and preparation method |
| CN113388569B (en) * | 2020-08-28 | 2022-05-17 | 广东乾晖生物科技有限公司 | Preparation method of liver organoid |
| CN113171490A (en) * | 2021-04-22 | 2021-07-27 | 中国医科大学 | Method for preparing hepatic precursor containing biliary tree structure by combining 3D printing and mold |
| CN113229993A (en) * | 2021-05-10 | 2021-08-10 | 中国医科大学 | Detachable combined die and method for preparing complex organ with multi-branch channel |
| CN113528337A (en) * | 2021-07-19 | 2021-10-22 | 中国医科大学 | Combined die for organ manufacturing and drug screening and use method thereof |
| CN113528338A (en) * | 2021-07-19 | 2021-10-22 | 中国医科大学 | Special combined die for drug screening and use method thereof |
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| CN1883420A (en) * | 2006-05-22 | 2006-12-27 | 西安交通大学 | A bionic liver tissue engineering scaffold and forming process thereof |
| CN102512261A (en) * | 2011-12-28 | 2012-06-27 | 清华大学 | Preparation method for complex organ precursors on basis of combination molds |
| CN102631709A (en) * | 2012-04-13 | 2012-08-15 | 清华大学 | Method for preparing complex organ precursor with branch vessel network |
| CN102908207A (en) * | 2012-10-30 | 2013-02-06 | 南通大学 | Tissue engineering nerve graft prepared by biological printing technology and preparation method thereof |
| CN104658395A (en) * | 2015-02-15 | 2015-05-27 | 清华大学 | Heart simulation structure as well as forming method and special mold thereof |
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| JP2016519609A (en) * | 2013-04-11 | 2016-07-07 | ユニヴァーシティ オブ フロリダ リサーチ ファウンデーション，インコーポレイテッドＵｎｉｖｅｒｓｉｔｙ Ｏｆ Ｆｌｏｒｉｄａ Ｒｅｓｅａｒｃｈ Ｆｏｕｎｄａｔｉｏｎ，Ｉｎｃ． | Organ component and method for producing the same |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1883420A (en) * | 2006-05-22 | 2006-12-27 | 西安交通大学 | A bionic liver tissue engineering scaffold and forming process thereof |
| CN102512261A (en) * | 2011-12-28 | 2012-06-27 | 清华大学 | Preparation method for complex organ precursors on basis of combination molds |
| CN102631709A (en) * | 2012-04-13 | 2012-08-15 | 清华大学 | Method for preparing complex organ precursor with branch vessel network |
| CN102908207A (en) * | 2012-10-30 | 2013-02-06 | 南通大学 | Tissue engineering nerve graft prepared by biological printing technology and preparation method thereof |
| CN104658395A (en) * | 2015-02-15 | 2015-05-27 | 清华大学 | Heart simulation structure as well as forming method and special mold thereof |
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