CN109333883B - Bionic ileum and preparation method thereof - Google Patents

Bionic ileum and preparation method thereof Download PDF

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CN109333883B
CN109333883B CN201811143747.7A CN201811143747A CN109333883B CN 109333883 B CN109333883 B CN 109333883B CN 201811143747 A CN201811143747 A CN 201811143747A CN 109333883 B CN109333883 B CN 109333883B
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ileum
biomimetic
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preparing
human
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CN109333883A (en
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詹晓北
李志涛
高敏杰
张文龙
徐静静
蒋芸
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Jiangnan University
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Priority to PCT/CN2018/117135 priority patent/WO2020062521A1/en
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Priority to US16/875,106 priority patent/US11721241B2/en
Priority to US18/325,338 priority patent/US12131665B2/en
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/38—Moulds or cores; Details thereof or accessories therefor characterised by the material or the manufacturing process
    • B29C33/3842—Manufacturing moulds, e.g. shaping the mould surface by machining
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C41/00—Shaping by coating a mould, core or other substrate, i.e. by depositing material and stripping-off the shaped article; Apparatus therefor
    • B29C41/02—Shaping by coating a mould, core or other substrate, i.e. by depositing material and stripping-off the shaped article; Apparatus therefor for making articles of definite length, i.e. discrete articles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C41/00—Shaping by coating a mould, core or other substrate, i.e. by depositing material and stripping-off the shaped article; Apparatus therefor
    • B29C41/34—Component parts, details or accessories; Auxiliary operations
    • B29C41/38—Moulds, cores or other substrates
    • G—PHYSICS
    • G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
    • G09B—EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
    • G09B23/00—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes
    • G09B23/28—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for medicine
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2083/00—Use of polymers having silicon, with or without sulfur, nitrogen, oxygen, or carbon only, in the main chain, as moulding material

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Abstract

The invention discloses a bionic ileum and a preparation method thereof, belonging to the technical field of bionics and the technical field of biology. The bionic ileum is prepared by mixing a base material (one or more of silica gel, latex or hydrogel) and an auxiliary material (silicone oil and/or a curing agent) according to a certain mass ratio and then smearing the mixture in the ileum of a precise human intestinal anatomical model in a medical digestive department; the bionic ileum has excellent simulation performance (the Shore A hardness is 32 +/-5, the expansion rate is 28 +/-5% and the elasticity is 220 +/-50%), has the shape and the physiological structure of the human real ileum, and can truly simulate the digestion environment in the ileum, for example, the bionic ileum has annular wrinkles inside, so that the intestinal surface area can be increased, the intestinal microflora in the ileum can better digest and absorb food, meanwhile, the bionic ileum has small intestinal villi inside and the small intestinal villi is of a hollow structure, so that intestinal fluid can be secreted, and the digestion and absorption functions in the ileum can be greatly reproduced.

Description

Bionic ileum and preparation method thereof
Technical Field
The invention relates to a bionic ileum and a preparation method thereof, belonging to the technical field of bionics and the technical field of biology.
Background
In the research process of food and medicine, the objective and accurate assessment of the digestion process of food and medicine in human body is important for determining the food components, medicine components and their effects on the digestive tract of human body.
The human digestive tract in-vitro simulation device (such as SHIME, IViDiS, TIM, DGM, HGS and the like) is a device for performing bionic simulation on the human digestive system, the digestive environment of the human digestive system and the dynamic behavior of fluid in the digestive tract, and can simulate the digestive processes of different samples in an in-vitro model and the influence of the samples on intestinal microorganisms, so that a large amount of valuable data is provided for the research and development of novel functional food, and if the device is used as a 'pretest' to predict a living test, the device can completely or partially replace the living test, and the purposes of reducing cost and time and improving repeatability and accuracy can be achieved without theoretical limitation.
Therefore, the human digestive tract in-vitro simulation device is more and more critical in the research of food, medicines, even microorganisms and the like, provides great convenience for the research of food science and human nutrition, and is incomparable to mouse experiments or human volunteer experiments.
The simulated digestive tract (mainly comprising stomach, small intestine and large intestine) is used as the main body of the human digestive tract in-vitro simulation device, and the simulation degree of the simulated digestive tract (mainly comprising stomach, small intestine and large intestine) on the human real digestive tract is of great importance in the simulation performance of the whole human digestive tract in-vitro simulation device.
At present, people usually use silica gel, latex and other materials to manufacture a simulated digestive tract model, and can well reproduce the digestive environment in the digestive tract, such as inviscid property, insolubility in water, no reaction with acid and alkali, high and low temperature resistance and the like.
However, the internal physiological structures of the existing digestive tract models made of silica gel and latex are smooth and unitary, for example, the small intestine models have the following structural defects: firstly, the small intestine has no villi, so that the food contact area in the intestine is too small, and the function of realizing digestion and absorption in the small intestine is limited; and secondly, the intestinal juice is embodied in a direct adding mode, and the intestinal juice is not secreted uniformly, so that the measurement result of the experiment is inaccurate.
Moreover, these digestive tract models are often simply fabricated as a monolithic structure, e.g., a whole stomach made of silicone or latex in one go, which cannot simulate the "reflux flow" function between the antrum and the body of the stomach, resulting in inaccurate experimental measurements.
Meanwhile, the digestive tract models made of silica gel and latex are actually unsatisfactory in simulation performance, such as hardness, expansion rate and elasticity, and still have a certain difference from the real digestive tract of a human.
Therefore, innovative upgrading of the bionic digestive tract is urgently needed to improve the simulation performance of the bionic digestive tract, improve the digestive environment (inviscid, insoluble in water, non-reactive with acid and alkali, and resistant to high and low temperatures) of the simulated real human digestive tract, and improve the authenticity of the functions of all parts of the digestive tract.
Disclosure of Invention
In order to solve the problems, the invention provides a bionic ileum and a preparation method thereof. The bionic ileum is prepared by mixing a base material (one or more of silica gel, latex or hydrogel) and an auxiliary material (silicone oil and/or a curing agent) according to a certain mass ratio (the mass ratio of the base material to the silicone oil to the curing agent is 100: 2.5-3.5: 0.5-1.5) and then smearing the mixture in an ileum of an accurate human intestinal anatomical model of a medical digestive department; the bionic ileum has excellent simulation performance (the Shore A hardness is 32 +/-5, the expansion rate is 28 +/-5% and the elasticity is 220 +/-50%), has the shape and the physiological structure of a human real ileum, and can truly simulate the digestion environment in the ileum of a human, for example, the inside of the bionic ileum is provided with annular folds which can increase the intestinal surface area so as to be used for better digesting and absorbing food by the microbial flora in the ileum, meanwhile, the inside of the bionic ileum is provided with small intestinal villi which are of a hollow structure and can secrete intestinal fluid so as to greatly reproduce the digestion and absorption functions in the ileum of the ileum, so that the bionic ileum can simulate the actual functions of food, medicine, microorganism and the like in the ileum of a digestion system, and has great application prospects in the research process of the food and the medicine.
The technical scheme of the invention is as follows:
the invention provides a preparation method of a bionic ileum, which comprises the steps of putting a plastic material into an accurate human ileum anatomical model of a medical gastroenterology department for modeling, taking down the human ileum anatomical model, poking a small hole at each dent of the plastic material, which corresponds to small intestinal villi on the human ileum anatomical model, continuously retaining the needle on the plastic material, and curing and molding the plastic material to obtain an ileum mold with a real ileum internal physiological structure; mixing the base material and the auxiliary material for preparing the bionic ileum according to a certain mass ratio to obtain a raw material of the bionic ileum; smearing the bionic ileum raw material on one surface of an ileum mould which is contacted with the human ileum anatomical model according to a certain thickness, standing to solidify and form the bionic ileum raw material smeared on the surface of the ileum mould, pulling out the needle-shaped object and removing the ileum mould to obtain a hollow bionic ileum with small intestinal villus;
or the method comprises the steps of placing the plastic material into an accurate human ileum anatomical model of the medical gastroenterology department for modeling, taking down the human ileum anatomical model, poking a small hole at each depression of the plastic material corresponding to the villi of the small intestine on the human ileum anatomical model by using a needle, continuously retaining the needle on the plastic material, and curing and molding the plastic material to obtain the ileum mold with the real ileum internal physiological structure; mixing the base material and the auxiliary material for preparing the bionic ileum according to a certain mass ratio to obtain a raw material of the bionic ileum; smearing the bionic ileum raw material on one surface of an ileum mould which is contacted with the human ileum anatomical model according to a certain thickness, standing to solidify and form the bionic ileum raw material smeared on the surface of the ileum mould, and only pulling out the needle-shaped object to obtain a hollow bionic ileum with small intestinal villus; covering a layer of isolator on the side of the bionic ileum not contacted with the ileum mould, coating the bionic ileum raw material on the side of the isolator not contacted with the bionic ileum according to a certain thickness, standing to solidify and form the bionic ileum raw material coated on the surface of the isolator, removing the isolator and removing the ileum mould to obtain the bionic ileum which has the ileum physiological structure villus and can secrete intestinal juice;
the substrate comprises one or more of a silica gel, a latex, or a hydrogel; the auxiliary material comprises silicone oil and/or a curing agent.
In one embodiment of the invention, the medical gastroenterology precision human intestinal anatomical model is a real intestinal 1:1 hollow model.
In one embodiment of the invention, the moldable material comprises china clay, paraffin, glass or steel.
In one embodiment of the invention, the moldable material comprises china clay, paraffin, glass or steel.
In one embodiment of the invention, the clay is soft clay.
In one embodiment of the invention, the method comprises the steps of putting the soft ceramic mud into a precise human ileum anatomical model of a medical gastroenterology department for modeling, taking down the human ileum anatomical model, poking a small hole in each depression of the soft ceramic mud corresponding to small intestine villi on the human ileum anatomical model by using a needle, continuously retaining the needle on the soft ceramic mud, baking the soft ceramic mud to enable the soft ceramic mud to be solidified and molded, and naturally cooling to prevent the mold from being rapidly cooled to generate cracks, so that an ileum mold with a real ileum internal physiological structure is obtained; mixing the base material and the auxiliary material for preparing the bionic ileum according to a certain mass ratio, and then putting the mixture into a vacuum machine for vacuumizing and bubble removal to obtain the raw material of the bionic ileum; smearing the bionic ileum raw material on the inner side of an ileum mould according to a certain thickness, standing to enable the bionic ileum raw material smeared on the surface of the ileum mould to be solidified and formed, pulling out a needle and removing the ileum mould to obtain a hollow bionic ileum with small intestinal villus;
or the method comprises the steps of firstly putting the soft ceramic mud into a precise human ileum anatomical model of a medical gastroenterology department for modeling, taking down the human ileum anatomical model, poking a small hole at each depression of the soft ceramic mud corresponding to intestinal villi on the human ileum anatomical model by using a needle-shaped object, continuously retaining the needle-shaped object on the soft ceramic mud, baking the soft ceramic mud to solidify and form the soft ceramic mud, and naturally cooling the soft ceramic mud to prevent the mould from being rapidly cooled to generate cracks, thereby obtaining the ileum mould with the internal physiological structure of the real ileum; mixing the base material and the auxiliary material for preparing the bionic ileum according to a certain mass ratio, and then putting the mixture into a vacuum machine for vacuumizing and bubble removal to obtain the raw material of the bionic ileum; smearing the bionic ileum raw material on the inner side of an ileum mould according to a certain thickness, standing to enable the bionic ileum raw material smeared on the surface of the ileum mould to be solidified and formed, and only pulling out a needle to obtain a hollow bionic ileum with small intestinal villus; covering a layer of isolator on the side of the bionic ileum not contacted with the ileum mould, coating bubble-free mixed raw materials on the side of the isolator not contacted with the bionic ileum according to a certain thickness, standing to solidify and form the bionic ileum raw materials coated on the surface of the isolator, removing the isolator and removing the ileum mould to obtain the bionic ileum with ileum physiological structure villus and capable of secreting intestinal juice.
In one embodiment of the present invention, the baking time is 15 to 30 min.
In one embodiment of the present invention, the diameter of the small hole is 0.2-1 mm
In one embodiment of the invention, the small hole is punched in each depression of the clayey clay corresponding to the villi of the small intestine of the anatomic model of the human ileum by penetrating the clayey clay with one end of the needle at least 2mm beyond the side of the clayey clay in contact with the anatomic model of the human ileum.
In one embodiment of the invention, the diameter of the ileal mold is 1.5-2.5 cm, and the length is 20-30 cm.
In one embodiment of the invention, the mass ratio of the base material, the silicone oil and the curing agent is 100 (2.5-3.5) to (0.5-1.5).
In one embodiment of the invention, the mass ratio between the base material and the auxiliary material is 100:3:1.
In one embodiment of the invention, the substrate is silica gel.
In one embodiment of the present invention, the silica gel is a transparent silica gel or a translucent silica gel.
In one embodiment of the invention, the curing agent comprises one or more of ethyl orthosilicate, vinyl triamine, DETA aminoethyl piperazine AE, m-phenylenediamine m-PDAMPD, diaminodiphenylmethane DDM, or HT-972 DEH-50.
In one embodiment of the invention, the conditions for vacuumizing and bubble removing are negative pressure of a vacuum machine of-0.1-0.09 MPa for 5-10 min.
In one embodiment of the invention, the conditions for vacuumizing and bubble discharging are vacuum of 0.09MPa for 7 min.
In one embodiment of the invention, the thickness of the bionic ileum raw material coated on the surface of the ileum mould is 2-3 mm.
In one embodiment of the invention, the thickness of the bionic ileum raw material applied on the surface of the ileal mould is 2.5 mm.
In one embodiment of the invention, the standing time is 2-4 h.
In one embodiment of the invention, the time of standing is 3 hours.
In one embodiment of the invention, the separator comprises an oily paper or a wrap film.
In one embodiment of the invention, the thickness of the bionic ileum raw material coated on the surface of the spacer is 2-3 mm.
In one embodiment of the invention, the thickness of the raw material of the bionic ileum coated on the surface of the spacer is 2.5 mm.
The invention provides a bionic ileum prepared by the preparation method of the bionic ileum.
The invention provides a preparation method of the bionic ileum or application of the bionic ileum prepared by the preparation method in simulating an actual digestive system of a human body.
Has the advantages that:
(1) the bionic ileum has excellent simulation performance (the Shore A hardness is 32 +/-5, the expansion rate is 28 +/-5%, and the elasticity is 220 +/-50%), has the shape and physiological structure of a real ileum of a human, and can truly simulate the digestion environment in the ileum of the human;
(2) the bionic ileum has annular wrinkles inside, so that the intestinal surface area can be increased, and the intestinal surface area can be better digested and absorbed by the microbial flora in the ileum;
(3) the bionic ileum has the advantages that small intestinal villi inside the bionic ileum can be of a double-layer hollow structure, and if intestinal fluid is filled into the hollow part, the small intestinal villi can automatically secrete the intestinal fluid in the peristalsis process, so that the digestion and absorption functions in the ileum can be greatly reproduced;
(4) the bionic ileum can be dynamic transparent or semitransparent, and can realize real and real-time in-vitro observation of the internal digestion state of the ileum;
(5) the bionic ileum takes silica gel as a base material, has the advantages of no viscosity, insolubility in water, no reaction with acid and alkali, high and low temperature resistance and the like, and can well reproduce the digestion and absorption environment in the intestine;
(6) the bionic ileum can simulate the real functions of food, medicine, microorganism and the like in the ileum of a digestive system, and has great application prospect in the research process of the food and the medicine.
Drawings
FIG. 1: the invention simulates the positive photograph of the ileum;
FIG. 2: the invention simulates the reverse photo of ileum;
FIG. 3: the invention simulates the small intestine villus photo of the ileum;
FIG. 4: the invention discloses a small intestine villus photo of a bionic ileum.
Detailed Description
The invention is further illustrated with reference to specific examples.
The detection methods referred to in the following examples are as follows:
the intestinal area detection method comprises the following steps:
S＝2πr1h1+n(π-1)r2h2；
wherein S is the intestinal area, r1Is the radius of the intestine, h1Is the height of the intestine, n is the number of intestinal walls, r2Is the radius of the intestinal wall, h2The intestinal wall is high.
The transparency detection method comprises the following steps:
by visual inspection, whether the silica gel is transparent and bright and has bubbles is observed, the silica gel is stretched to see whether the silica gel is whitish or not, the silica gel is opaque or whitish, and foods such as rice, corn and the like are placed in the silica gel to see whether the appearances of the foods can be clearly seen or not.
If the surface of the food can be clearly seen, the transparency is good; if the outline of the food can be seen, the transparency is moderate; if the object image of the food is not visible, the transparency is poor.
Hardness (shore hardness) detection method:
the measurement was performed using a Shore durometer with the indenter pin pressed against the surface of the stomach and the depth of penetration of the indenter pin into the stomach surface was measured.
The expansion rate detection method comprises the following steps:
Pe＝(W*m/A)×100％；
wherein Pe is the expansion ratio, W is the total equilibrium load, A is the silica gel area, and m is the lever ratio of the pressurizing equipment.
The elasticity detection method comprises the following steps:
and (3) performing a tensile test on the silica gel on a tensile testing machine, and measuring the axial elongation and the transverse elongation of the silica gel until the silica gel is broken.
C＝(D-d)×100％/d；
Wherein C is the elastic modulus, D is the elongation, and D is the initial length of the silica gel.
And (3) testing the function of villus secretion intestinal juice:
the obtained bionic duodenum is fixed in an intestinal visual bionic reactor (the intestinal visual bionic reactor is disclosed in the invention patent with the publication number of CN 108318625A) through a flange interface of a pipeline, 100ml of pancreatic juice is added into the silica gel bionic duodenum, the reactor is operated for 10min, and the volume of the secreted pancreatic juice is observed.
Example 1: preparation of biomimetic ileum
(1) Preparing clay: repeatedly kneading the soft clay to obtain soft clay with good ductility;
(2) ileum mould pressing: placing the kneaded soft ceramic mud into an accurate human ileum anatomical model of a medical gastroenterology department, forcibly extruding, and taking down the human ileum anatomical model to obtain a soft ceramic mud ileum mold with a real ileum internal physiological structure, wherein the diameter of the mold is 1.5cm, and the length of the mold is 25 cm;
(3) manufacturing hollow fluff: pricking a plurality of needles with diameter of 0.5mm into each mark of the mold, pricking small holes with diameter of 1mm and depth of 5mm, and keeping the needles in the mold
(4) Baking and forming an ileum mold: placing the ileum mould into an oven for baking for 15 minutes at the temperature of 140 ℃ to solidify and form the ileum mould, and naturally cooling to obtain a bionic ileum mould;
(8) preparing silica gel: putting transparent silica gel, silicone oil and curing agent tetraethoxysilane in a beaker according to the ratio of 100:3:1, fully stirring and uniformly mixing;
(9) putting the uniformly mixed silica gel into a vacuum machine, vacuumizing and discharging bubbles for 5 minutes under the negative pressure of 0.09MPa to obtain bubble-free silica gel;
(10) uniformly coating bubble-free silica gel with the thickness of about 2mm on the surface of the bionic ileum mould;
(11) standing the uniformly coated ileum mold for 2 hours to completely solidify and mold the ileum mold, and pulling out a needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;
(12) covering an oily paper on the surface of the ileum mould which is only pulled out of the needle and does not fall off the silica gel, placing a hollow cylinder with the diameter of 2cm and the height of 4cm on the outer side, and fixing and sticking the cylinder;
(13) uniformly coating bubble-free silica gel in a gap between the oily paper of the ileum mould and the cylinder, standing for 2 hours, and completely solidifying and forming;
(14) placing the solidified silica gel mold in water for 10 minutes, and taking the oily paper out of the hollow cylinder after the oily paper is softened by the water;
(15) after the ileum mold is removed from the silica gel, the bionic ileum silica gel model which has ileum physiological structure intestinal wall wrinkles and villi and can secrete intestinal fluid can be obtained through certain pruning treatment.
Example 2: preparation of biomimetic ileum
(1) Preparing clay: repeatedly kneading the soft clay to obtain soft clay with good ductility;
(2) ileum mould pressing: placing the kneaded soft ceramic mud into an accurate human ileum anatomical model of a medical gastroenterology department, forcibly extruding, and taking down the human ileum anatomical model to obtain a soft ceramic mud ileum mold with a real ileum internal physiological structure, wherein the mold has the diameter of 2cm and the length of 25 cm;
(3) manufacturing hollow fluff: pricking a plurality of needles with diameter of 0.3mm into each mark of the mold, pricking small holes with diameter of 0.5mm and depth of 5mm, and keeping the needles in the mold
(4) Baking and forming an ileum mold: placing the ileum mould into an oven to bake for 20 minutes at 150 ℃ to solidify and form the ileum mould, and naturally cooling to obtain a bionic ileum mould;
(8) preparing silica gel: putting transparent silica gel, silicone oil and curing agent vinyl triamine in a ratio of 100:3:1.5 into a beaker, fully stirring and uniformly mixing;
(9) putting the uniformly mixed silica gel into a vacuum machine, vacuumizing and discharging bubbles for 5 minutes under the negative pressure of 0.09MPa to obtain bubble-free silica gel;
(10) uniformly coating bubble-free silica gel with the thickness of about 2.5mm on the surface of the bionic ileum mould;
(11) standing the uniformly coated ileum mold for 4 hours to completely solidify and mold the ileum mold, and pulling out a needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;
(12) covering an oily paper on the surface of the ileum mould which is only pulled out of the needle and does not fall off the silica gel, placing a hollow cylinder with the diameter of 2cm and the height of 4cm on the outer side, and fixing and sticking the cylinder;
(13) uniformly coating bubble-free silica gel in a gap between the oily paper of the ileum mould and the cylinder, standing for 1 hour, and completely solidifying and forming;
(14) placing the solidified silica gel mold in water for 10 minutes, and taking the oily paper out of the hollow cylinder after the oily paper is softened by the water;
(15) after the ileum mold is removed from the silica gel, the bionic ileum silica gel model which has ileum physiological structure intestinal wall wrinkles and villi and can secrete intestinal fluid can be obtained through certain pruning treatment.
Example 3: preparation of biomimetic ileum
(1) Preparing clay: repeatedly kneading the soft clay to obtain soft clay with good ductility;
(2) ileum mould pressing: placing the kneaded soft ceramic mud into an accurate human ileum anatomical model of a medical gastroenterology department, forcibly extruding, and taking down the human ileum anatomical model to obtain a soft ceramic mud ileum mold with a real ileum internal physiological structure, wherein the diameter of the mold is 2.5cm, and the length of the mold is 30 cm;
(3) manufacturing hollow fluff: pricking a plurality of needles with diameter of 0.1mm into each mark of the mold, pricking small holes with diameter of 0.2mm and depth of 5mm, and keeping the needles in the mold
(4) Baking and forming an ileum mold: placing the ileum mould into an oven to bake for 30 minutes at 130 ℃ to solidify and form the ileum mould, and naturally cooling to obtain a bionic ileum mould;
(8) preparing silica gel: putting transparent silica gel, silicone oil and a curing agent diaminodiphenylmethane DDM in a beaker according to a ratio of 100:2.5:1, fully stirring and uniformly mixing;
(9) putting the uniformly mixed silica gel into a vacuum machine, vacuumizing and discharging bubbles for 5 minutes under the negative pressure of 0.09MPa to obtain bubble-free silica gel;
(10) uniformly coating bubble-free silica gel with the thickness of about 3mm on the surface of the bionic ileum mould;
(11) standing the uniformly coated ileum mold for 1 hour to completely solidify and mold the ileum mold, and pulling out a needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;
(12) covering an oily paper on the surface of the ileum mould which is only pulled out of the needle and does not fall off the silica gel, placing a hollow cylinder with the diameter of 2cm and the height of 4cm on the outer side, and fixing and sticking the cylinder;
(13) uniformly coating bubble-free silica gel in a gap between the oily paper of the ileum mould and the cylinder, standing for 1 hour, and completely solidifying and forming;
(14) placing the solidified silica gel mold in water for 10 minutes, and taking the oily paper out of the hollow cylinder after the oily paper is softened by the water;
(15) after the ileum mold is removed from the silica gel, the bionic ileum silica gel model which has ileum physiological structure intestinal wall wrinkles and villi and can secrete intestinal fluid can be obtained through certain pruning treatment.
Comparative example 1: preparation of bionic ileum (without villus)
(1) Preparing clay: repeatedly kneading the soft clay to obtain soft clay with good ductility;
(2) ileum mould pressing: placing the kneaded soft ceramic mud into an accurate human ileum anatomical model of a medical gastroenterology department, forcibly extruding, and taking down the human ileum anatomical model to obtain a soft ceramic mud ileum mold with a real ileum internal physiological structure, wherein the diameter of the mold is 2.5cm, and the length of the mold is 30 cm;
(4) baking and forming an ileum mold: placing the ileum mould into an oven to bake for 30 minutes at 130 ℃ to solidify and form the ileum mould, and naturally cooling to obtain a bionic ileum mould;
(8) preparing silica gel: putting transparent silica gel, silicone oil and curing agent tetraethoxysilane in a beaker according to the proportion of 100:3.5:0.5, fully stirring and uniformly mixing;
(9) putting the uniformly mixed silica gel into a vacuum machine, vacuumizing and discharging bubbles for 5 minutes under the negative pressure of 0.09MPa to obtain bubble-free silica gel;
(10) uniformly coating bubble-free silica gel with the thickness of about 2.5mm on the surface of the bionic ileum mould;
(11) standing the uniformly coated ileum mold for 1 hour to completely solidify and mold;
(15) after the ileum mold is removed from the silica gel, the bionic ileum silica gel model with the ileum physiological structure intestinal wall wrinkles can be obtained through certain pruning treatment.
Comparative example 2: preparation of bionic ileum (silica gel after mixing without vacuum)
(1) Preparing clay: repeatedly kneading the soft clay to obtain soft clay with good ductility;
(2) ileum mould pressing: placing the kneaded soft ceramic mud into an accurate human ileum anatomical model of a medical gastroenterology department, forcibly extruding, and taking down the human ileum anatomical model to obtain a soft ceramic mud ileum mold with a real ileum internal physiological structure, wherein the mold has the diameter of 2cm and the length of 30 cm;
(3) manufacturing hollow fluff: pricking a plurality of needles with diameter of 0.2mm into each mark of the mold, pricking small holes with diameter of 0.5mm and depth of 5mm, and keeping the needles in the mold
(4) Baking and forming an ileum mold: placing the ileum mould into an oven to bake for 20 minutes at the temperature of 140 ℃, solidifying and forming the ileum mould, and naturally cooling to obtain a bionic ileum mould;
(8) preparing silica gel: putting transparent silica gel, silicone oil and curing agent tetraethoxysilane in a beaker according to the ratio of 100:3:0.5, fully stirring and uniformly mixing;
(9) uniformly coating silica gel on the surface of the bionic ileum mould with the thickness of about 2.5 mm;
(10) standing the uniformly coated ileum mold for 2 hours to completely solidify and mold the ileum mold, and pulling out a needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;
(11) covering an oily paper on the surface of the ileum mould which is only pulled out of the needle and does not fall off the silica gel, placing a hollow cylinder with the diameter of 2cm and the height of 4cm on the outer side, and fixing and sticking the cylinder;
(12) uniformly coating bubble-free silica gel in a gap between the oily paper of the ileum mould and the cylinder, standing for 2 hours, and completely solidifying and forming;
(13) placing the solidified silica gel mold in water for 10 minutes, and taking the oily paper out of the hollow cylinder after the oily paper is softened by the water;
(14) after the ileum mold is removed from the silica gel, the bionic ileum silica gel model which has ileum physiological structure intestinal wall wrinkles and villi and can secrete intestinal fluid can be obtained through certain pruning treatment.
Comparative example 3: preparation of bionic ileum (thickness increase of silica gel coating)
(1) Preparing clay: repeatedly kneading the soft clay to obtain soft clay with good ductility;
(2) ileum mould pressing: placing the kneaded soft ceramic mud into an accurate human ileum anatomical model of a medical gastroenterology department, forcibly extruding, and taking down the human ileum anatomical model to obtain a soft ceramic mud ileum mold with a real ileum internal physiological structure, wherein the mold has the diameter of 2cm and the length of 30 cm;
(3) manufacturing hollow fluff: pricking a plurality of needles with diameter of 0.4mm into each mark of the mold, pricking small holes with diameter of 0.6mm and depth of 5mm, and keeping the needles in the mold
(4) Baking and forming an ileum mold: placing the ileum mould into an oven to bake for 30 minutes at 130 ℃ to solidify and form the ileum mould, and naturally cooling to obtain a bionic ileum mould;
(8) preparing silica gel: putting transparent silica gel, silicone oil and curing agent tetraethoxysilane in a beaker according to the ratio of 100:2.5:1.5, fully stirring and uniformly mixing;
(9) putting the uniformly mixed silica gel into a vacuum machine, vacuumizing and discharging bubbles for 5 minutes under the negative pressure of 0.09MPa to obtain bubble-free silica gel;
(10) uniformly coating bubble-free silica gel with the thickness of about 6mm on the surface of the bionic ileum mould;
(11) standing the uniformly coated ileum mold for 2 hours to completely solidify and mold the ileum mold, and pulling out a needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;
(12) covering an oily paper on the surface of the ileum mould which is only pulled out of the needle and does not fall off the silica gel, placing a hollow cylinder with the diameter of 2cm and the height of 4cm on the outer side, and fixing and sticking the cylinder;
(13) uniformly coating bubble-free silica gel in a gap between the oily paper of the ileum mould and the cylinder, standing for 2 hours, and completely solidifying and forming;
(14) placing the solidified silica gel mold in water for 10 minutes, and taking the oily paper out of the hollow cylinder after the oily paper is softened by the water;
(15) after the ileum mold is removed from the silica gel, the bionic ileum silica gel model which has ileum physiological structure intestinal wall wrinkles and villi and can secrete intestinal fluid can be obtained through certain pruning treatment.
Comparative example 4: preparation of bionic ileum (without silicone oil)
(1) Preparing clay: repeatedly kneading the soft clay to obtain soft clay with good ductility;
(2) ileum mould pressing: placing the kneaded soft ceramic mud into an accurate human ileum anatomical model of a medical gastroenterology department, forcibly extruding, and taking down the human ileum anatomical model to obtain a soft ceramic mud ileum mold with a real ileum internal physiological structure, wherein the mold has the diameter of 2cm and the length of 30 cm;
(3) manufacturing hollow fluff: pricking a plurality of needles with diameter of 0.4mm into each mark of the mold, pricking small holes with diameter of 0.6mm and depth of 5mm, and keeping the needles in the mold
(4) Baking and forming an ileum mold: placing the ileum mould into an oven to bake for 30 minutes at 130 ℃ to solidify and form the ileum mould, and naturally cooling to obtain a bionic ileum mould;
(8) preparing silica gel: putting transparent silica gel and curing agent tetraethoxysilane in a beaker according to the ratio of 100:1, fully stirring and uniformly mixing;
(9) putting the uniformly mixed silica gel into a vacuum machine, vacuumizing and discharging bubbles for 5 minutes under the negative pressure of 0.09MPa to obtain bubble-free silica gel;
(10) uniformly coating bubble-free silica gel with the thickness of about 2mm on the surface of the bionic ileum mould;
(11) standing the uniformly coated ileum mold for 2 hours to completely solidify and mold the ileum mold, and pulling out a needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;
(12) covering an oily paper on the surface of the ileum mould which is only pulled out of the needle and does not fall off the silica gel, placing a hollow cylinder with the diameter of 2cm and the height of 4cm on the outer side, and fixing and sticking the cylinder;
(13) uniformly coating bubble-free silica gel in a gap between the oily paper of the ileum mould and the cylinder, standing for 2 hours, and completely solidifying and forming;
(14) placing the solidified silica gel mold in water for 10 minutes, and taking the oily paper out of the hollow cylinder after the oily paper is softened by the water;
(15) after the ileum mold is removed from the silica gel, the bionic ileum silica gel model which has ileum physiological structure intestinal wall wrinkles and villi and can secrete intestinal fluid can be obtained through certain pruning treatment.
Comparative example 5: preparation of bionic ileum (with glycerol)
(1) Preparing clay: repeatedly kneading the soft clay to obtain soft clay with good ductility;
(2) ileum mould pressing: placing the kneaded soft ceramic mud into an accurate human ileum anatomical model of a medical gastroenterology department, forcibly extruding, and taking down the human ileum anatomical model to obtain a soft ceramic mud ileum mold with a real ileum internal physiological structure, wherein the mold has the diameter of 2cm and the length of 30 cm;
(3) manufacturing hollow fluff: pricking a plurality of needles with diameter of 0.4mm into each mark of the mold, pricking small holes with diameter of 0.6mm and depth of 5mm, and keeping the needles in the mold
(4) Baking and forming an ileum mold: placing the ileum mould into an oven to bake for 30 minutes at 130 ℃ to solidify and form the ileum mould, and naturally cooling to obtain a bionic ileum mould;
(8) preparing silica gel: putting transparent silica gel, glycerol and curing agent tetraethoxysilane in a beaker according to the ratio of 100:3:1, fully stirring and uniformly mixing;
(9) putting the uniformly mixed silica gel into a vacuum machine, vacuumizing and discharging bubbles for 5 minutes under the negative pressure of 0.09MPa to obtain bubble-free silica gel;
(10) uniformly coating bubble-free silica gel with the thickness of about 2mm on the surface of the bionic ileum mould;
(11) standing the uniformly coated ileum mold for 2 hours to completely solidify and mold the ileum mold, and pulling out a needle outside the mold to obtain a hollow ileum silica gel model with small intestinal villi;
(12) covering an oily paper on the surface of the ileum mould which is only pulled out of the needle and does not fall off the silica gel, placing a hollow cylinder with the diameter of 2cm and the height of 4cm on the outer side, and fixing and sticking the cylinder;
(13) uniformly coating bubble-free silica gel in a gap between the oily paper of the ileum mould and the cylinder, standing for 2 hours, and completely solidifying and forming;
(14) placing the solidified silica gel mold in water for 10 minutes, and taking the oily paper out of the hollow cylinder after the oily paper is softened by the water;
(15) after the ileum mold is removed from the silica gel, the bionic ileum silica gel model which has ileum physiological structure intestinal wall wrinkles and villi and can secrete intestinal fluid can be obtained through certain pruning treatment.
Example 4: detection of a biomimetic ileum
The anatomical model of human ileum with the same length, the bionic ileum prepared in examples 1-3, the bionic ileum prepared in comparative examples 1-5 and the similar products in foreign countries (the Fast 3 type silica gel bionic ileum purchased from Dragon Skin company in USA) are taken to carry out intestinal area, transparency, hardness, expansion rate, elasticity detection and villus function detection, and the detection results are shown in Table 1.
As can be seen from Table 1, the indexes of the bionic ileum are closer to those of the real ileum, and the indexes of the bionic ileum are better than those of similar products abroad, so that the bionic ileum can replace the real ileum to predict a living body test, completely replace or partially replace the living body test, and achieve the purposes of reducing cost and time and improving repeatability and accuracy without theoretical limitation.
TABLE 1 Performance test results
Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.

Claims (44)

1. A preparation method of a bionic ileum is characterized in that a plastic material is placed into an accurate human ileum anatomical model of a medical gastroenterology department for modeling, the human ileum anatomical model is taken down, small holes are poked at each dent of the plastic material corresponding to small intestine villi on the human ileum anatomical model by a needle, the needle is continuously kept on the plastic material, and the plastic material is solidified and molded, so that an ileum mold with a real ileum internal physiological structure is obtained; mixing the base material and the auxiliary material for preparing the bionic ileum according to a certain mass ratio to obtain a raw material of the bionic ileum; smearing the bionic ileum raw material on one surface of an ileum mould which is contacted with the human ileum anatomical model according to a certain thickness, standing to solidify and form the bionic ileum raw material smeared on the surface of the ileum mould, pulling out the needle-shaped object and removing the ileum mould to obtain a hollow bionic ileum with small intestinal villus;
or the method comprises the steps of placing the plastic material into an accurate human ileum anatomical model of the medical gastroenterology department for modeling, taking down the human ileum anatomical model, poking a small hole at each depression of the plastic material corresponding to the villi of the small intestine on the human ileum anatomical model by using a needle, continuously retaining the needle on the plastic material, and curing and molding the plastic material to obtain the ileum mold with the real ileum internal physiological structure; mixing the base material and the auxiliary material for preparing the bionic ileum according to a certain mass ratio to obtain a raw material of the bionic ileum; smearing the bionic ileum raw material on one surface of an ileum mould which is contacted with the human ileum anatomical model according to a certain thickness, standing to solidify and form the bionic ileum raw material smeared on the surface of the ileum mould, and only pulling out the needle-shaped object to obtain a hollow bionic ileum with small intestinal villus; covering a layer of isolator on the side of the bionic ileum not contacted with the ileum mould, coating the bionic ileum raw material on the side of the isolator not contacted with the bionic ileum according to a certain thickness, standing to solidify and form the bionic ileum raw material coated on the surface of the isolator, removing the isolator and removing the ileum mould to obtain the bionic ileum which has the ileum physiological structure villus and can secrete intestinal juice;
the substrate comprises one or more of a silica gel, a latex, or a hydrogel; the auxiliary material comprises silicone oil and/or a curing agent.
2. The method of claim 1, wherein the plastic material comprises china clay, paraffin, glass or steel.
3. The method for preparing a biomimetic ileum according to claim 1 or 2, wherein the diameter of the small hole is 0.2-1 mm.
4. The method of claim 1, wherein the holes are punched in the plastic material at each depression corresponding to the villi of the small intestine of the anatomic model of the human ileum by allowing the pins to penetrate the plastic material and extend at least 2mm from the side of the plastic material in contact with the anatomic model of the human ileum.
5. The method of claim 2, wherein the holes are punched in the plastic material at each depression corresponding to the villi of the small intestine of the anatomic model of the human ileum by allowing the pins to penetrate the plastic material and extend at least 2mm from the side of the plastic material in contact with the anatomic model of the human ileum.
6. A method of preparing a simulated ileum as claimed in claim 3 wherein the pin is caused to penetrate the plastics material and extend at least 2mm beyond the face of the plastics material which contacts the anatomical model of the human ileum when a small hole is made in each depression of the plastics material which corresponds to the villi in the small intestine of the anatomical model of the human ileum.
7. The method for preparing a biomimetic ileum according to claim 1, wherein the mass ratio of the base material, the silicone oil and the curing agent is 100 (2.5-3.5) to 0.5-1.5.
8. The method for preparing a bionic ileum as claimed in claim 2, wherein the mass ratio of the base material, the silicone oil and the curing agent is 100 (2.5-3.5) to (0.5-1.5).
9. The method for preparing a bionic ileum as claimed in claim 3, wherein the mass ratio of the base material, the silicone oil and the curing agent is 100 (2.5-3.5) to (0.5-1.5).
10. The method for preparing a biomimetic ileum according to claim 4, wherein the mass ratio of the base material, the silicone oil and the curing agent is 100 (2.5-3.5) to (0.5-1.5).
11. The method for preparing a biomimetic ileum according to claim 1, wherein the raw material of the biomimetic ileum is applied to the ileal mold after vacuuming and bubbling; the conditions of vacuumizing and bubble discharging are negative pressure of a vacuum machine of-0.1-0.09 MPa and 5-10 min.
12. The method for preparing a biomimetic ileum according to claim 2, wherein the raw material of the biomimetic ileum is applied to the ileal mold after vacuuming and bubbling; the conditions of vacuumizing and bubble discharging are negative pressure of a vacuum machine of-0.1-0.09 MPa and 5-10 min.
13. The method for preparing a biomimetic ileum according to claim 3, wherein the raw material of the biomimetic ileum is applied to the ileal mold after vacuuming and bubbling; the conditions of vacuumizing and bubble discharging are negative pressure of a vacuum machine of-0.1-0.09 MPa and 5-10 min.
14. The method for preparing a biomimetic ileum according to claim 4, wherein the raw material of the biomimetic ileum is applied to the ileal mold after vacuuming and bubbling; the conditions of vacuumizing and bubble discharging are negative pressure of a vacuum machine of-0.1-0.09 MPa and 5-10 min.
15. The method for preparing a biomimetic ileum according to claim 5, wherein the raw material of the biomimetic ileum is applied to the ileal mold after vacuuming and bubbling; the conditions of vacuumizing and bubble discharging are negative pressure of a vacuum machine of-0.1-0.09 MPa and 5-10 min.
16. The method for preparing a biomimetic ileum according to claim 1, wherein the thickness of the raw material of the biomimetic ileum coated on the surface of the ileum mold is 2-3 mm.
17. The method for preparing a biomimetic ileum according to claim 2, wherein the thickness of the raw material of the biomimetic ileum coated on the surface of the ileum mold is 2-3 mm.
18. The method for preparing a biomimetic ileum according to claim 3, wherein the thickness of the raw material of the biomimetic ileum coated on the surface of the ileum mold is 2-3 mm.
19. The method for preparing a biomimetic ileum according to claim 4, wherein the thickness of the raw material of the biomimetic ileum coated on the surface of the ileum mold is 2-3 mm.
20. The method for preparing a biomimetic ileum according to claim 5, wherein the thickness of the raw material of the biomimetic ileum coated on the surface of the ileum mold is 2-3 mm.
21. The method for preparing a biomimetic ileum according to claim 6, wherein the thickness of the raw material of the biomimetic ileum coated on the surface of the ileum mold is 2-3 mm.
22. The method for preparing a biomimetic ileum according to claim 1, wherein the standing time is 2-4 h.
23. The method for preparing a biomimetic ileum according to claim 2, wherein the standing time is 2-4 h.
24. The method for preparing a biomimetic ileum according to claim 3, wherein the standing time is 2-4 h.
25. The method for preparing a biomimetic ileum according to claim 4, wherein the standing time is 2-4 h.
26. The method for preparing a biomimetic ileum according to claim 5, wherein the standing time is 2-4 h.
27. The method for preparing a biomimetic ileum according to claim 6, wherein the standing time is 2-4 h.
28. The method for preparing a biomimetic ileum according to claim 7, wherein the standing time is 2-4 h.
29. The biomimetic ileum prepared by the preparation method of the biomimetic ileum in claim 1.
30. The biomimetic ileum prepared by the preparation method of the biomimetic ileum in claim 2.
31. The biomimetic ileum prepared by the preparation method of the biomimetic ileum in claim 3.
32. The biomimetic ileum prepared by the preparation method of the biomimetic ileum in claim 4.
33. The bionic ileum prepared by the preparation method of the bionic ileum of claim 5.
34. The biomimetic ileum prepared by the preparation method of the biomimetic ileum in claim 6.
35. The biomimetic ileum prepared by the preparation method of the biomimetic ileum in claim 7.
36. The biomimetic ileum prepared by the preparation method of the biomimetic ileum in claim 8.
37. Use of a method of making a biomimetic ileum according to claim 1 or a biomimetic ileum made according to any of claims 29-36 to simulate an actual digestive system in a human.
38. Use of a method of preparing a biomimetic ileum according to claim 2 or a biomimetic ileum prepared according to any of claims 29-36 to simulate an actual digestive system in a human.
39. Use of a method of preparing a biomimetic ileum according to claim 3 or a biomimetic ileum prepared according to any of claims 29-36 to simulate an actual digestive system in a human.
40. Use of a method of preparing a biomimetic ileum according to claim 4 or a biomimetic ileum prepared according to any of claims 29-36 to simulate an actual digestive system in a human.
41. Use of a method of preparing a biomimetic ileum according to claim 5 or a biomimetic ileum prepared according to any of claims 29-36 to simulate an actual digestive system in a human.
42. Use of a method of preparing a biomimetic ileum according to claim 6 or a biomimetic ileum prepared according to any of claims 29-36 to simulate an actual digestive system in a human.
43. Use of a method of preparing a biomimetic ileum according to claim 7 or a biomimetic ileum prepared according to any of claims 29-36 to simulate an actual digestive system in a human.
44. Use of a method of preparing a biomimetic ileum according to claim 8 or a biomimetic ileum prepared according to any of claims 29-36 to simulate an actual digestive system in a human.
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