CN115645614B - Preparation method of skull repairing material for children - Google Patents

Preparation method of skull repairing material for children Download PDF

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Publication number
CN115645614B
CN115645614B CN202211404533.7A CN202211404533A CN115645614B CN 115645614 B CN115645614 B CN 115645614B CN 202211404533 A CN202211404533 A CN 202211404533A CN 115645614 B CN115645614 B CN 115645614B
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collagen
skull
mixed solution
solution
titanium
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CN115645614A (en
Inventor
崔云
宋天喜
胡艳丽
朱金亮
何志敏
仇志烨
崔孟龙
吴晶晶
胡刚
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Weifang Aojing Medical Research Co ltd
Aojing Medical Technology Co ltd
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Weifang Aojing Medical Research Co ltd
Aojing Medical Technology Co ltd
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    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P10/00Technologies related to metal processing
    • Y02P10/25Process efficiency

Abstract

The invention relates to the technical field of skull repairing materials, in particular to a preparation method of a child skull repairing material. The embodiment of the invention provides a preparation method of a child skull repair material, which comprises the following steps: obtaining skull model data of a child patient, and obtaining a die of a skull broken shape through 3D printing according to the skull model data; adding mineralized collagen into the first collagen gel solution to obtain a mixed solution; the side, facing the cranium, of the mold faces upwards, and a layered titanium metal net is placed in the mold, wherein the titanium metal net has elasticity; injecting the mixed solution into a mold to obtain a first repairing layer; and injecting a second collagen gel solution onto the first repairing layer to obtain a second repairing layer, and freeze-drying to obtain the skull repairing material for children. The embodiment of the invention provides a preparation method of a skull repairing material for children, which can provide a skull repairing material with strong mechanical property and deformation capability.

Description

Preparation method of skull repairing material for children
Technical Field
The invention relates to the technical field of skull repairing materials, in particular to a preparation method of a child skull repairing material.
Background
When the skull defect range of the child patient is large, the skull needs to be repaired by the skull repairing material.
In the related art, the skull repairing material is mineralized collagen. However, the skull of the child patient is continuously grown and deformed, mineralized collagen is gradually degraded and synchronously regenerated with bone tissue, but the mechanical properties and deformability of mineralized collagen cannot meet the demands of growth and deformation of the child skull due to deformation, poor mechanical strength of the new bone tissue and the like.
Therefore, in order to overcome the above disadvantages, a method for preparing a skull repairing material for children is urgently needed.
Disclosure of Invention
The embodiment of the invention provides a preparation method of a skull repairing material for children, which can provide a skull repairing material with strong mechanical property and deformation capability.
The embodiment of the invention provides a preparation method of a child skull repair material, which comprises the following steps:
obtaining skull model data of a child patient, and obtaining a die of a skull broken shape through 3D printing according to the skull model data;
adding mineralized collagen into the first collagen gel solution to obtain a mixed solution;
the side, facing the cranium, of the mold faces upwards, and a layered titanium metal net is placed in the mold, wherein the titanium metal net has elasticity;
injecting the mixed solution into a mold to obtain a first repairing layer;
and injecting a second collagen gel solution onto the first repairing layer to obtain a second repairing layer, and freeze-drying to obtain the skull repairing material for children.
In one possible design, the titanium metal net comprises titanium strips and connecting parts, the titanium strips are connected in a head-to-tail mode through rivets in a rotating mode to form serrated titanium chains, the titanium chains can stretch or shrink, and the connecting parts of a plurality of rivets connected with adjacent titanium chains connect a plurality of adjacent titanium chains to form the titanium metal net.
In one possible design, the connection comprises a connecting rod connected in a head-to-tail rotational manner.
In one possible design, the first collagen gel solution has a solids content of 2.8 to 3.25%.
In one possible design, the mass ratio of collagen to mineralized collagen in the mixed solution is 100: (55-60).
In one possible design, after the obtaining of the mixed solution and before the injecting of the mixed solution into the mold, comprises:
glycerol was added to the mixed solution.
In one possible design, the mass ratio of collagen to glycerol in the mixed solution is 100: (10-15).
In one possible design, the second collagen gel aqueous solution has a solids content of 1.5 to 2%.
In one possible design, the thickness of the second repair layer is 1 to 3mm.
In one possible design, after the lyophilization process, further comprising:
the method comprises the steps of crosslinking treatment, water washing treatment and vacuum drying, wherein the crosslinking treatment comprises soaking the freeze-dried material by glutaraldehyde solution.
Compared with the prior art, the invention has at least the following beneficial effects:
in the embodiment, the titanium metal mesh is added into the skull repairing material, and is wrapped in the skull repairing material as a framework, so that the titanium metal mesh can provide excellent mechanical properties, and meanwhile, the titanium has low density and no toxicity, and does not increase the burden on patients. The expansion and contraction of the titanium metal net enables the skull repairing material to be capable of adaptively deforming along with the growth of the skull of the child, and the requirement of the growth and deformation of the skull of the child can be met.
In this embodiment, the first repair layer includes collagen and mineralized collagen, both of which have biocompatibility and degradability, and have excellent porosity, so that the bone repair layer is beneficial to the crawling growth of new bone cells, the mineralized collagen includes elements such as Ca and P, and the elements such as Ca and P are released in the degradation process of the mineralized collagen, and the elements are beneficial to the formation of new bone cells and the acceleration of the repair rate of the skull. The second collagen layer comprises collagen, the collagen has the characteristic of swelling by absorbing water, the second collagen layer faces one side in the cranium, after the cranium is repaired by using the composite material, if cerebrospinal fluid leaks, the second collagen layer swells after absorbing a small amount of cerebrospinal fluid rapidly, and hydrostatic pressure is provided to press dura mater, so that the cerebrospinal fluid is prevented from further leaking.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a flow chart of a method for preparing a child skull repair material provided by an embodiment of the invention;
FIG. 2 is a flow chart of another method for preparing a child skull repair material provided by an embodiment of the present invention;
FIG. 3 is a schematic structural view of a child skull repair material provided by an embodiment of the present invention;
fig. 4 is a schematic structural view of a titanium metal mesh according to an embodiment of the present invention.
In the figure:
1-a first repair layer;
2-a second repair layer;
3-titanium metal mesh;
31-titanium chain;
311-titanium bars;
32-a connection;
321-connecting rods.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments, and all other embodiments obtained by those skilled in the art without making any inventive effort based on the embodiments of the present invention are within the scope of protection of the present invention.
In the description of embodiments of the present invention, the terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying any relative importance unless explicitly specified or limited otherwise; the term "plurality" means two or more, unless specified or indicated otherwise; the terms "connected," "secured," and the like are to be construed broadly, and may be, for example, fixedly connected, detachably connected, integrally connected, or electrically connected; can be directly connected or indirectly connected through an intermediate medium. The specific meaning of the above terms in the present invention can be understood by those of ordinary skill in the art according to the specific circumstances.
In the description of the present specification, it should be understood that the terms "upper", "lower", and the like used in the embodiments of the present invention are described in terms of the angles shown in the drawings, and should not be construed as limiting the embodiments of the present invention. In the context of this document, it will also be understood that when an element is referred to as being "on" or "under" another element, it can be directly on the other element or be indirectly on the other element through intervening elements.
As shown in fig. 1 and 3, the embodiment of the invention provides a preparation method of a skull repairing material for children, which comprises the following steps:
step 100, obtaining skull model data of a child patient, and obtaining a die of a broken skull shape through 3D printing according to the skull model data;
step 102, adding mineralized collagen into a first collagen gel solution to obtain a mixed solution;
104, placing a layered titanium metal net 3 into the mould, wherein one side of the mould facing the cranium faces upwards, and the titanium metal net 3 has elasticity;
step 106, injecting the mixed solution into a mold to obtain a first repair layer 1;
and step 108, injecting a second collagen gel solution onto the first repairing layer 1 to obtain a second repairing layer 2, and freeze-drying to obtain the skull repairing material for children.
In the embodiment, the titanium metal mesh 3 is added into the skull repairing material, the titanium metal mesh 3 is used as a framework to be wrapped in the skull repairing material, the titanium metal mesh 3 can provide excellent mechanical properties, and meanwhile, the titanium has low density and no toxicity, and does not add burden to a patient. The expansion and contraction of the titanium metal net 3 enables the skull repairing material to adaptively deform along with the growth of the skull of the child, and can meet the requirement of the growth and deformation of the skull of the child.
In this embodiment, the first repair layer 1 includes collagen and mineralized collagen, both of which have biocompatibility and degradability, and have excellent porosity, so that the bone repair layer is beneficial to the crawling growth of new bone cells, the mineralized collagen includes elements such as Ca and P, and the elements such as Ca and P are released in the degradation process of the mineralized collagen, and the elements are beneficial to the formation of new bone cells and the acceleration of the repair rate of the skull. The second collagen layer comprises collagen, the collagen has the characteristic of swelling by absorbing water, the second collagen layer faces one side in the cranium, after the cranium is repaired by using the composite material, if cerebrospinal fluid leaks, the second collagen layer swells after absorbing a small amount of cerebrospinal fluid rapidly, and hydrostatic pressure is provided to press dura mater, so that the cerebrospinal fluid is prevented from further leaking.
In this embodiment, the process of making the mold includes:
and perfecting routine examination before operation and obtaining CT imaging data. And obtaining a skull defect model through three-dimensional software analysis, and completing the extraction of the implanted bone fragments through virtual operation design. The data of the bone block to be implanted is sent to a material 3D printer, and the PC or PMMA material is used for completing the model preparation of the personalized implant. And turning the model according to the 3D printed skull model, and customizing a personalized mold.
In this embodiment, the collagen is preferably type I collagen, and the preparation method of type I collagen includes:
(1) Removing superfluous fascia, fat, muscle and the like on the beef achilles tendon, washing with tap water, and orderly arranging in a freezing box for freezing at-20 ℃ for at least 12 hours;
(2) Cutting frozen Achilles tendon into slices of about 1mm, and placing into a filter screen for turning and washing until the liquid is clear;
(3) Enzymolysis: carrying out enzymolysis on the cleaned beef achilles tendon slices, and fully stirring, wherein the enzymolysis time is not less than 72 hours; wherein the mass ratio of the enzymolysis liquid to the bovine Achilles tendon is 130:1, the volume ratio of purified water to acetic acid in the enzymolysis liquid is 25:1, the mass ratio of the purified water to the pepsin is 15:1.
(4) Salting out: centrifuging the solution after enzymolysis, taking supernatant, adding the supernatant into sodium chloride solution, separating out white flocculent collagen, filtering and cleaning, and draining water.
(5) And (3) dialysis: filling the salted-out material into a dialysis bag, wherein the filling volume is about 1/3 of that of the dialysis bag; placing the dialysis bag in 0.057mol/L acetic acid solution for 6 days, and changing the dialysis solution every 3 days at 10-20deg.C; then placing the dialysis bag in 0.00057mol/L acetic acid solution for dialysis for 5 days, wherein the dialysis temperature is 10-20 ℃, and the dialysate is changed every 1 day; dialyzing in 0.0000057mol/L acetic acid solution from day 12 to pH 5.5-5.5, and dialyzing at 10-20deg.C, and changing dialysate once daily as required.
(6) Freeze-drying
The sample is subjected to a freeze-drying process comprising a pre-freezing stage, a first sublimation stage, a second sublimation stage and a cooling stage, wherein the process conditions of each stage are as follows:
pre-freezing: the target temperature is-12 to-8 ℃, the speed is 3-4.0 ℃/min, and the constant temperature duration is 280-320 min;
a first sublimation stage: vacuumizing, aerating at 90-110 Pa, wherein the target temperature is-4 to-2 ℃, the speed is 0.6-0.8 ℃/min, and the constant temperature duration is 1300-1340 min;
in the second sublimation stage, vacuumizing, and aerating at 90-110 Pa, wherein the second sublimation stage comprises five temperature rising steps of respectively:
-1 ℃, the speed is 0.2-0.3 ℃/min, and the constant temperature duration is 110-130 min;
8-12 ℃, the speed is 1.0-1.2 ℃/min, and the constant temperature duration is 110-130 min;
the temperature is 18-22 ℃, the speed is 1.0-1.2 ℃/min, and the constant temperature duration is 110-130 min;
28-32 ℃, the speed is 1.0-1.2 ℃/min, and the constant temperature duration is 110-130 min;
38-42 ℃, the speed is 1.0-1.2 ℃/min, and the constant temperature duration is as follows: performing end point judgment every 10 minutes until the end point judgment is qualified; judging the end point to be less than or equal to 0.9Pa/10min;
and (3) a cooling stage: cooling to room temperature at a speed of 1.4-1.6 ℃/min;
and obtaining the collagen sponge raw material.
It should be noted that all lyophilization processes of the present invention can use the lyophilization process described above.
The preparation method of mineralized collagen comprises the following steps:
step 1, dissolving collagen in any one of hydrochloric acid, nitric acid or acetic acid to prepare an acid solution of the collagen, wherein the concentration of the collagen is 0.01-0.2 g/ml;
step 2, dropwise adding a calcium salt solution into the acid solution of the collagen, wherein the adding amount of calcium ions is 0.1-2 mol of calcium ions added into each gram of collagen;
step 3, dropwise adding a phosphoric acid solution into the solution obtained in the step 2, wherein the molar ratio of the adding amount of phosphate ions to the adding amount of calcium ions in the step S1-2 is Ca/P=1/1-2/1;
step 4, dropwise adding a NaOH solution into the solution obtained in the step 3 to form a mixed solution, and regulating the pH value to be 6-8;
step 5, standing the mixed solution obtained in the step 4 for 4-12 hours, centrifuging at a speed of 3000-6000 r/min to obtain precipitate, and drying at 50-70 ℃ for 24-72 hours by air blast to obtain mineralized collagen particles;
and step 6, placing the mineralized collagen particles obtained in the step 5 into a crucible for grinding until no obvious particles exist, and obtaining mineralized collagen powder.
In this embodiment, the preparation method of the collagen gel solution includes:
(1) Weighing type I collagen: firstly, placing a weighing device on an electronic balance, pressing a return-to-zero key, placing type I collagen on the weighing device, and weighing a certain amount of type I collagen. Weighing and rechecking the weighed type I collagen on a balance again;
(2) Recording the mass of the type I collagen as m1;
(3) Swelling collagen type I: swelling the weighed type I collagen in a homogenizer with a volume of purified water;
swelling was carried out for 24 hours, during which stirring was continued at a frequency of 25 Hz.
In this example, in order to uniformly disperse and mix mineralized collagen in the first collagen gel solution, mineralized collagen was added in several portions, each at intervals of 20min, during which stirring was continued at a frequency of 25Hz, wall-mounted powder was scraped into the mixture every 30min, while a spatula was used to extend from the bottom of the homogenizing shaft, transparent unblended type I collagen was scraped out, and mixed with other type I collagen, and stirring was continued. Adding bone powder again, repeating the above steps, and homogenizing.
As shown in fig. 4, in some embodiments of the present invention, the titanium metal mesh 3 includes titanium strips 311 and connecting portions 32, the titanium strips 311 are connected end to end by rivets to form serrated titanium chains 31, the titanium chains 31 can be expanded or contracted, and the connecting portions 32 of the rivets connecting adjacent titanium chains 31 connect the plurality of adjacent titanium chains 31 to form the titanium metal mesh 3.
In the present embodiment, the titanium mesh 3 is formed by the plurality of telescopic titanium chains 31 through the connecting portion 32, so that the titanium chain 31 composed of the plurality of titanium strips 311 has stretchability, and further the titanium mesh 3 composed of the titanium chains 31 also has stretchability.
In some embodiments of the present invention, the connection 32 includes a connection 321 that is rotationally coupled end-to-end.
In this embodiment, the titanium chain 31 enables the titanium mesh 3 to stretch in the first direction, and the plurality of connecting portions 321 are rotatably connected to form the connecting portion 32, so that the titanium mesh 3 can stretch in the second direction, and further the titanium mesh 3 can stretch in the plane thereof.
In some embodiments of the invention, the first collagen gel solution has a solids content of 2.8 to 3.25%.
In this embodiment, the first collagen gel solution forms the first repair layer 1, and the first repair layer 1 is an outer layer, and needs to have a certain strength, so the solid content is 2.8-3.25%, if the solid content is less than 2.8%, the strength of the first repair layer 1 is low, and if the solid content is more than 3.25%, the fluidity of the first collagen gel solution is poor, gaps exist at the contact interface with the titanium metal mesh 3, and the obtained first repair layer 1 has low porosity, which is unfavorable for rapid repair of the skull.
In some embodiments of the invention, the mass ratio of collagen to mineralized collagen in the mixed solution is 100: (55-60).
In this example, mineralized collagen was uniformly dispersed in collagen, and thus the mass ratio of collagen to mineralized collagen was 100: (55-60) if the mass ratio of collagen to mineralized collagen is higher than the above range, the mineralized collagen is too small, the effect of promoting the growth of new bone cells is not obvious, and if the mass ratio of collagen to mineralized collagen is lower than the above range, the collagen is small, it is difficult to disperse mineralized collagen uniformly, and the properties of the obtained material are not uniform, and cracking is easy.
In some embodiments of the invention, after obtaining the mixed solution and before injecting the mixed solution into the mold, comprising:
glycerol was added to the mixed solution.
In this example, glycerol was added to more uniformly mix collagen and mineralized collagen, the mixing efficiency was higher, and cracking of the material could be prevented in the subsequent lyophilization process.
In some embodiments of the invention, the mass ratio of collagen to glycerol in the mixed solution is 100: (10-15).
In this example, if the mass ratio of collagen to glycerol is higher than the above range, the effect of glycerol is not obvious, and if the mass ratio of collagen to glycerol is lower than the above range, the mechanical properties of the skull repairing material are lowered.
In some embodiments of the invention, the solids content of the second aqueous collagen gel solution is 1.5-2%.
In this embodiment, if the solid content of the second collagen gel aqueous solution is less than 1.5%, the supporting property of the prepared second repairing layer 2 is poor, and if the solid content of the second collagen gel aqueous solution is more than 2%, the porosity of the prepared second repairing layer 2 is low.
In some embodiments of the invention, the thickness of the second repair layer 2 is 1-3 mm.
In this embodiment, if the thickness of the second repair layer 2 is less than 1mm, it is difficult to provide enough hydrostatic pressure to prevent the cerebrospinal fluid from further leakage, and if the thickness of the second repair layer 2 is more than 1 to 3mm, the overall strength of the repair material may be too low.
In some embodiments of the invention, after the lyophilization process, further comprising:
the method comprises the steps of crosslinking treatment, water washing treatment and vacuum drying, wherein the crosslinking treatment comprises soaking the freeze-dried material by glutaraldehyde solution.
In this embodiment, the crosslinking treatment includes:
(1) Preparing a cross-linking agent solution: measuring a certain volume of absolute ethyl alcohol by using a measuring cylinder, transferring the absolute ethyl alcohol into a reaction kettle, and transferring a certain volume of glutaraldehyde (the mass fraction of glutaraldehyde is 50%) by using a pipette to prepare an absolute ethyl alcohol solution of glutaraldehyde with a certain concentration;
absolute ethanol (M1) =m (mass of collagen and mineralized collagen in mixed solution) ×200mL
Glutaraldehyde (M1) =m (mass of collagen and mineralized collagen in mixed solution)/10 (mL)
(2) The freeze-dried material is soaked in the absolute ethanol solution of glutaraldehyde (the specific dosage is calculated according to an electronic version feeding table), the stirring speed of a reaction kettle is 20-30r/min, and the material can rotate along with stirring and is crosslinked for 48 hours.
In this embodiment, the water washing treatment includes:
(1) Taking the crosslinked material out of the crosslinking agent solution;
(2) The centrifuge loads the filter bag and centrifuges once (5 seconds); the rotational speed of the centrifugal machine defaults to 3000r/min;
(3) Completely soaking the material with 3% hydrogen peroxide solution for 42+ -1 h, wherein the soaking ratio is 1:80, namely 3% hydrogen peroxide solution volume (ml) =product quality (g) ×80;
(4) Purified water is subjected to ultrasonic treatment for 30min, and is centrifuged once (5 s) after ultrasonic treatment; repeating for 2 times;
(5) And (3) carrying out ultrasonic treatment on absolute ethyl alcohol for 5 minutes, wherein the volume of absolute ethyl alcohol is based on the principle of immersing the product, and carrying out centrifugal operation once (5 seconds) after ultrasonic treatment is finished.
The vacuum drying comprises the following steps:
and (3) loading the centrifuged material into a vacuum drying oven for vacuum drying, wherein the vacuum degree is not higher than-0.08 Mpa, the temperature is set to be 50 ℃, and the drying is carried out for at least 24 hours.
As shown in fig. 2, the embodiment of the invention further provides a preparation method of another skull repairing material for children, which comprises the following steps:
step 200, obtaining skull model data of a child patient, and obtaining a die of a broken skull shape through 3D printing according to the skull model data;
step 202, adding mineralized collagen into a first collagen gel solution to obtain a mixed solution; wherein the solid content of the first collagen gel solution is 2.8-3.25%, and the mass ratio of collagen to mineralized collagen in the mixed solution is 100: (55-60);
step 204, adding glycerol into the mixed solution, wherein the mass ratio of the collagen in the mixed solution to the glycerol is 100: (10-15);
step 206, placing a layered titanium metal net 3 into the mould, wherein one side of the mould facing the cranium is upward, and the titanium metal net 3 has elasticity;
step 208, injecting the mixed solution into a mold to obtain a first repair layer 1;
step 210, injecting a second collagen gel solution onto the first repair layer 1, wherein the solid content of the second collagen gel solution is 1.5-2%, so as to obtain a second repair layer 2;
step 212, obtaining the skull repairing material for children after freeze-drying, crosslinking, water washing and vacuum drying.
In order to more clearly illustrate the technical scheme and advantages of the invention, a method for preparing a skull repairing material is described in detail through several embodiments.
Example 1
Obtaining skull model data of a child patient, and obtaining a die of a skull broken shape through 3D printing according to the skull model data;
adding mineralized collagen into the first collagen gel solution to obtain a mixed solution; wherein the solid content of the first collagen gel solution is 2.8%, and the mass ratio of collagen to mineralized collagen in the mixed solution is 100:55;
adding glycerol into the mixed solution, wherein the mass ratio of the collagen in the mixed solution to the glycerol is 100:10;
the side, facing the cranium, of the mold faces upwards, and a layered titanium metal net is placed in the mold, wherein the titanium metal net has elasticity;
injecting the mixed solution into a mold to obtain a first repairing layer;
injecting a second collagen gel solution onto the first repairing layer, wherein the solid content of the second collagen gel solution is 1.5%, so as to obtain a second repairing layer;
freeze-drying, cross-linking, water washing and vacuum drying to obtain the skull repairing material for children.
Example 2
Obtaining skull model data of a child patient, and obtaining a die of a skull broken shape through 3D printing according to the skull model data;
adding mineralized collagen into the first collagen gel solution to obtain a mixed solution; wherein the solid content of the first collagen gel solution is 3%, and the mass ratio of collagen to mineralized collagen in the mixed solution is 100:57;
adding glycerol into the mixed solution, wherein the mass ratio of the collagen in the mixed solution to the glycerol is 100:12.5;
the side, facing the cranium, of the mold faces upwards, and a layered titanium metal net is placed in the mold, wherein the titanium metal net has elasticity;
injecting the mixed solution into a mold to obtain a first repairing layer;
injecting a second collagen gel solution onto the first repairing layer, wherein the solid content of the second collagen gel solution is 1.7%, so as to obtain a second repairing layer;
freeze-drying, cross-linking, water washing and vacuum drying to obtain the skull repairing material for children.
Example 3
Obtaining skull model data of a child patient, and obtaining a die of a skull broken shape through 3D printing according to the skull model data;
adding mineralized collagen into the first collagen gel solution to obtain a mixed solution; wherein the solid content of the first collagen gel solution is 3.25%, and the mass ratio of collagen to mineralized collagen in the mixed solution is 100:60;
adding glycerol into the mixed solution, wherein the mass ratio of the collagen in the mixed solution to the glycerol is 100:15;
the side, facing the cranium, of the mold faces upwards, and a layered titanium metal net is placed in the mold, wherein the titanium metal net has elasticity;
injecting the mixed solution into a mold to obtain a first repairing layer;
injecting a second collagen gel solution onto the first repairing layer, wherein the solid content of the second collagen gel solution is 2%, so as to obtain a second repairing layer;
freeze-drying, cross-linking, water washing and vacuum drying to obtain the skull repairing material for children.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (9)

1. A method for preparing a skull repair material for children, which is characterized by comprising the following steps:
obtaining skull model data of a child patient, and obtaining a die of a skull broken shape through 3D printing according to the skull model data;
adding mineralized collagen into the first collagen gel solution to obtain a mixed solution;
the side of the mould facing the cranium is upward, a layered titanium metal net (3) is put into the mould, and the titanium metal net (3) has elasticity;
injecting the mixed solution into a mould to obtain a first repairing layer (1);
injecting a second collagen gel solution onto the first repairing layer (1) to obtain a second repairing layer (2), and freeze-drying to obtain a child skull repairing material;
the solid content of the first collagen gel solution is 2.8-3.25%.
2. The manufacturing method according to claim 1, wherein the titanium metal mesh (3) comprises titanium strips (311) and connecting parts (32), the titanium strips (311) are connected end to end through rivets in a rotating way to form serrated titanium chains (31), the titanium chains (31) can be expanded or contracted, and the connecting parts (32) of a plurality of rivets connecting adjacent titanium chains (31) connect a plurality of adjacent titanium chains (31) to form the titanium metal mesh (3).
3. The method of manufacturing according to claim 2, characterized in that the connection (32) comprises a connecting rod (321) connected end to end in a rotating manner.
4. The preparation method according to claim 1, wherein the mass ratio of collagen to mineralized collagen in the mixed solution is 100: (55-60).
5. The method according to claim 1, characterized by comprising, after said obtaining a mixed solution and before said injecting said mixed solution into a mold:
glycerol was added to the mixed solution.
6. The method according to claim 5, wherein the mass ratio of the collagen to the glycerol in the mixed solution is 100: (10-15).
7. The method according to claim 1, wherein the solid content of the second collagen gel solution is 1.5 to 2%, and the second collagen gel solution is a second collagen gel aqueous solution.
8. The preparation method according to claim 1, characterized in that the thickness of the second repair layer (2) is 1-3 mm.
9. The method according to claim 1, characterized by further comprising, after the lyophilization treatment:
the method comprises the steps of crosslinking treatment, water washing treatment and vacuum drying, wherein the crosslinking treatment comprises soaking the freeze-dried material by glutaraldehyde solution.
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