CN115645614A - Preparation method of children skull repairing material - Google Patents

Preparation method of children skull repairing material Download PDF

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Publication number
CN115645614A
CN115645614A CN202211404533.7A CN202211404533A CN115645614A CN 115645614 A CN115645614 A CN 115645614A CN 202211404533 A CN202211404533 A CN 202211404533A CN 115645614 A CN115645614 A CN 115645614A
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collagen
skull
mixed solution
titanium
repairing
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CN202211404533.7A
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CN115645614B (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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    • 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 children skull repairing material. The embodiment of the invention provides a preparation method of a children skull repairing material, which comprises the following steps: obtaining skull model data of a child patient, and obtaining a skull damage shape mould 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 intracranial faces upwards, and a layered titanium metal net is placed into the mould, 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 performing freeze-drying treatment to obtain the children skull repairing material. The embodiment of the invention provides a preparation method of a children skull repairing material, and the skull repairing material with strong mechanical property and deformation capability can be provided.

Description

Preparation method of children skull repairing material
Technical Field
The invention relates to the technical field of skull repairing materials, in particular to a preparation method of a children skull repairing material.
Background
When the skull defect range of the child patient is large, the skull needs to be repaired by the aid of skull repair materials.
In the related art, the skull repairing material is mineralized collagen. However, the skull of a child patient can grow and deform continuously, the gradual degradation of mineralized collagen and the regeneration of bone tissues are performed synchronously, but due to the deformation, the poor mechanical strength of new bone tissues and the like, the mechanical property and the deformation capability of the mineralized collagen cannot meet the requirements of the growth and the deformation of the skull of the child.
Therefore, in order to overcome the above disadvantages, a method for preparing a children skull repairing material is urgently needed.
Disclosure of Invention
The embodiment of the invention provides a preparation method of a children skull repairing material, and the skull repairing material with strong mechanical property and deformation capability can be provided.
The embodiment of the invention provides a preparation method of a children skull repairing material, which comprises the following steps:
obtaining skull model data of a child patient, and obtaining a skull damage shape mould 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 intracranial faces upwards, and a layered titanium metal net is placed into the mould, 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 performing freeze-drying treatment to obtain the children skull repairing material.
In one possible design, the titanium metal net comprises titanium strips and connecting parts, the titanium strips are connected end to end in a rotating mode through rivets to form zigzag titanium chains, the titanium chains can stretch or contract, and the connecting parts of a plurality of rivets for connecting adjacent titanium chains connect the adjacent titanium chains to form the titanium metal net.
In one possible design, the connecting portion comprises a connecting rod that is rotationally connected end to end.
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 the mixed solution and before the injecting the mixed solution into the mold, the method includes:
glycerol was added to the mixed solution.
In one possible design, the mass ratio of collagen and glycerol in the mixed solution is 100: (10 to 15).
In one possible design, the second aqueous collagen gel 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, the method further comprises:
and the crosslinking treatment comprises the steps of soaking the freeze-dried material by using a glutaraldehyde solution, and washing and vacuum drying.
Compared with the prior art, the invention at least has the following beneficial effects:
in the embodiment, the titanium metal net is added into the skull repairing material and is wrapped in the skull repairing material as a framework, so that the titanium metal net can provide excellent mechanical properties, and meanwhile, the titanium is low in density and non-toxic, and cannot increase burden on patients. The flexibility of the titanium metal mesh enables the skull repairing material to deform adaptively along with the growth of the children skull, and the requirement of the growth deformation of the children skull can be met.
In this embodiment, the first repairing layer includes collagen and mineralized collagen, both of which have biocompatibility and degradability, the collagen has excellent porosity and is beneficial to the crawling growth of new bone cells, the mineralized collagen includes elements such as Ca and P, 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 repairing rate of the skull. The second collagen layer includes collagen, and collagen has the characteristics that absorb water and swell, and the second collagen layer is towards intracranial one side, uses combined material to restore the skull back, if the cerebrospinal fluid reveals, the second collagen layer swells after absorbing water a small amount of cerebrospinal fluid fast to provide hydrostatic pressure oppression dura mater, prevent that the cerebrospinal fluid from further revealing.
Drawings
In order to more clearly illustrate the embodiments or technical solutions of the present invention, the drawings used in the embodiments or technical solutions in the prior art are briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to these drawings without creative efforts.
FIG. 1 is a flow chart of a method for preparing a children skull repairing material according to an embodiment of the present invention;
FIG. 2 is a flow chart of another method for preparing a children skull repairing material according to an embodiment of the present invention;
FIG. 3 is a schematic structural diagram of a children skull repairing material provided by an embodiment of the invention;
fig. 4 is a schematic structural diagram of a titanium metal mesh provided in an embodiment of the present invention.
In the figure:
1-a first repair layer;
2-a second repair layer;
3-titanium metal mesh;
a 31-titanium chain;
311-titanium strip;
32-a connecting portion;
321-connecting rod.
Detailed Description
To make the objects, technical solutions and advantages of the embodiments of the present invention clearer and more complete, the technical solutions in the embodiments of the present invention will be described below with reference to the drawings in the embodiments of the present invention, it is obvious that the described embodiments are some, but not all embodiments of the present invention, and based on the embodiments of the present invention, all other embodiments obtained by a person of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.
In the description of the embodiments of the present invention, unless explicitly specified or limited otherwise, the terms "first", "second", and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance; the term "plurality" means two or more unless otherwise specified or indicated; the terms "connected", "fixed", and the like are to be construed broadly and may, for example, be fixed or removable or integral or electrical; may be directly connected or indirectly connected through an intermediate. The specific meanings of the above terms in the present invention can be understood according to specific situations by those of ordinary skill in the art.
In the description of the present invention, it should be understood that the directional terms such as "upper" and "lower" used in the embodiments of the present invention are described with reference to the angles shown in the drawings, and should not be construed as limiting the embodiments of the present invention. In addition, in this context, it will also be understood that when an element is referred to as being "on" or "under" another element, it can be directly on "or" under "the other element or be indirectly on" or "under" the other element via an intermediate element.
As shown in fig. 1 and 3, an embodiment of the present invention provides a method for preparing a children skull repairing material, including:
step 100, obtaining skull model data of a child patient, and obtaining a skull damage shape mould 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, putting the layered titanium metal net 3 into the mold with the side of the mold facing the intracranial upwards, wherein the titanium metal net 3 has elasticity;
step 106, injecting the mixed solution into a mold to obtain a first repairing layer 1;
and 108, injecting a second collagen gel solution onto the first repairing layer 1 to obtain a second repairing layer 2, and performing freeze-drying treatment to obtain the children skull repairing material.
In the embodiment, the titanium metal mesh 3 is added into the skull repairing material, the titanium metal mesh 3 is wrapped in the skull repairing material as a framework, the titanium metal mesh 3 can provide excellent mechanical properties, and meanwhile, the titanium is low in density and non-toxic, and does not increase burden on patients. The flexibility of the titanium metal mesh 3 enables the skull repairing material to deform adaptively along with the growth of the children skull, and the requirement of the growth deformation of the children skull can be met.
In this embodiment, the first repairing layer 1 includes collagen and mineralized collagen, both of which have biocompatibility and degradability, the collagen has excellent porosity and is beneficial to the crawling growth of new bone cells, the mineralized collagen includes elements such as Ca and P, 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 repairing rate of the skull. The second collagen layer includes collagen, and collagen has the characteristics that absorb water and swell, and the second collagen layer is towards intracranial one side, uses combined material to restore the skull back, if the cerebrospinal fluid reveals, the second collagen layer swells after absorbing water a small amount of cerebrospinal fluid fast to provide hydrostatic pressure oppression dura mater, prevent that the cerebrospinal fluid from further revealing.
In this embodiment, the process of making the mold includes:
and (4) completing routine examination before operation and acquiring CT (computed tomography) imaging data. Analyzing by three-dimensional software to obtain a skull defect model, and completing the step of extracting the implanted bone blocks by virtual surgery design. And sending the data of the bone block to be implanted to a material 3D printer, and completing model preparation of the personalized implant by using a PC or PMMA material. And (5) performing rollover according to the 3D printed skull model, and customizing a personalized mold.
In this embodiment, the collagen is preferably type I collagen, and the method for producing type I collagen comprises:
(1) Removing redundant fascia, fat, muscle and the like on the bovine achilles tendon, washing with tap water, neatly arranging in a freezing box, freezing at-20 ℃ for at least 12h;
(2) Cutting frozen bovine achilles tendon into slices of about 1mm, placing in a filter screen, and washing until the liquid is clear;
(3) Enzymolysis: carrying out enzymolysis on the cleaned bovine achilles tendon slices, and fully stirring for not less than 72h; 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: and centrifuging the solution after enzymolysis, taking supernatant, adding the supernatant into a sodium chloride solution to separate out white flocculent collagen, filtering and washing, 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 a dialysate of 0.057mol/L acetic acid solution for 6 days, surreptitiously heating to 10-20 deg.C, and replacing the dialysate every 3 days; 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 replaced every 1 day; dialyzing in 0.0000057mol/L acetic acid solution at pH of 5.5-5.5 from day 12, wherein the dialysis temperature is 10-20 deg.C, and changing the dialysate once a day as required.
(6) Freeze-drying
The sample is subjected to freeze drying process, wherein the freeze drying process comprises a prefreezing stage, a first sublimation stage, a second sublimation stage and a temperature reduction stage, and the process conditions of each stage are as follows:
a pre-freezing stage: the target temperature is-12 to-8 ℃, the speed is 3 to 4.0 ℃/min, and the constant temperature duration is 280 to 320min;
a first sublimation stage: vacuumizing, wherein the air entrainment is 90-110 Pa, the target temperature is-4-2 ℃, the speed is 0.6-0.8 ℃/min, and the constant temperature duration is 1300-1340 min;
the second sublimation stage, vacuumization, 90-110 Pa aeration, including five temperature-rising steps, respectively:
the temperature is between-1 and 1 ℃, the speed is between 0.2 and 0.3 ℃/min, and the constant temperature duration is between 110 and 130min;
the temperature is 8-12 ℃, the speed is 1.0-1.2 ℃/min, and the constant temperature duration is 110-130 min;
at the temperature of 18-22 ℃, the speed is 1.0-1.2 ℃/min, and the constant temperature duration is 110-130 min;
the temperature is between 28 and 32 ℃, the speed is between 1.0 and 1.2 ℃/min, and the constant temperature duration is between 110 and 130min;
38-42 ℃, the speed is 1.0-1.2 ℃/min, the constant temperature duration is as follows: judging the end point every 10 minutes until the end point is judged to be qualified; the end point is judged to be less than or equal to 0.9Pa/10min;
and (3) cooling: cooling to room temperature at a rate of 1.4-1.6 deg.C/min;
obtaining the collagen sponge raw material.
It should be noted that all lyophilization processes of the present invention can be used with the above lyophilization process.
The preparation method of the 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 addition amount of calcium ions is 0.1-2 mol per gram of the collagen;
step 3, dropwise adding a phosphoric acid solution into the solution obtained in the step 2, wherein the molar ratio of the addition amount of phosphate ions to the addition amount of calcium ions in the step S1-2 is Ca/P = 1/1-2/1;
step 4, dripping NaOH solution into the solution obtained in the step 3 to form a mixed solution, and adjusting the pH value to 6-8;
step 5, standing the mixed solution obtained in the step 4 for 4-12 hours, centrifuging at the speed of 3000-6000 r/min to obtain precipitates, and performing air blast drying at the temperature of 50-70 ℃ for 24-72 hours to obtain mineralized collagen particles;
and 6, putting the mineralized collagen particles obtained in the step 5 into a crucible for grinding until no obvious particles exist, so as to obtain mineralized collagen powder.
In this example, the method of preparing the collagen gel solution includes:
(1) Weighing type I collagen: firstly, a weighing instrument is placed on an electronic balance, a zeroing key is pressed, the type I collagen is placed on the weighing instrument, and a certain amount of type I collagen is weighed. Putting the weighed I-type collagen on a balance again, weighing and rechecking;
(2) Recording the mass of the I-type collagen as m1;
(3) Swelling type I collagen: swelling the weighed I-type collagen in a homogenizer filled with a certain volume of purified water;
the mixture was allowed to swell for 24 hours, during which time it was stirred at a frequency of 25 Hz.
In this example, in order to uniformly disperse and mix the mineralized collagen in the first collagen gel solution, the mineralized collagen was added in multiple portions, each at 20min intervals, with stirring at a frequency of 25Hz, and the wall-hanging powder was scraped into the mixture every 30min, while the wall-hanging powder was simultaneously inserted from the bottom of the homogenizing shaft with a spatula, and the transparent unblended type I collagen was scraped out, mixed with other type I collagen, and further stirred. Adding the bone meal again, and repeating the above steps without opening homogenization.
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 zigzag-shaped titanium chains 31, the titanium chains 31 can be expanded or contracted, and the connecting portions 32 of the plurality of 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 expanded metal 3 is formed by the plurality of stretchable titanium chains 31 through the connecting portions 32, so that the titanium chains 31 composed of the plurality of titanium strips 311 have stretchability, and further, the titanium expanded metal 3 composed of the titanium chains 31 also has stretchability.
In some embodiments of the invention, the coupling portion 32 comprises a coupling portion 321 that is rotationally coupled end-to-end.
In this embodiment, the titanium chain 31 enables the titanium metal net 3 to expand and contract along the first direction, and the connecting portions 32 formed by the plurality of connecting portions 321 through rotation connection enable the titanium metal net 3 to expand and contract along the second direction, so that the titanium metal net 3 can expand and contract 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 repairing layer 1, the first repairing layer 1 is an outer layer, and a certain strength is required, so that the solid content is 2.8 to 3.25%, if the solid content is lower than 2.8%, the strength of the first repairing layer 1 is low, if the solid content is higher than 3.25%, the fluidity of the first collagen gel solution is poor, a gap exists at a contact interface with the titanium metal mesh 3, and the porosity of the obtained first repairing layer 1 is low, which is not favorable for rapid repairing 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, the mineralized collagen was uniformly dispersed in the 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 amount of mineralized collagen is too small, and the effect of promoting the growth of new bone cells is not significant, and if the mass ratio of collagen to mineralized collagen is lower than the above range, the amount of collagen is small, and the mineralized collagen is difficult to be uniformly dispersed, so that the properties of the prepared material are not uniform, and the material is easy to crack.
In some embodiments of the present invention, after obtaining the mixed solution and before injecting the mixed solution into the mold, the method comprises:
glycerol was added to the mixed solution.
In this example, the addition of glycerol allowed more uniform mixing of collagen and mineralized collagen, more efficient mixing, and prevented cracking of the material during subsequent freeze-drying.
In some embodiments of the invention, the mass ratio of collagen to glycerol in the mixed solution is 100: (10-15).
In the present example, if the mass ratio of collagen to glycerin is higher than the above range, the effect of glycerin is not significant, and if the mass ratio of collagen to glycerin is lower than the above range, the mechanical properties of the skull repairing material are degraded.
In some embodiments of the invention, the second aqueous collagen gel solution has a solids content of 1.5 to 2%.
In this example, if the solid content of the second aqueous collagen gel solution is less than 1.5%, the prepared second prosthetic layer 2 has poor support, and if the solid content of the second aqueous collagen gel solution is higher than 2%, the prepared second prosthetic layer 2 has low porosity.
In some embodiments of the invention, the thickness of the second repair layer 2 is 1 to 3mm.
In the embodiment, if the thickness of the second repairing layer 2 is less than 1mm, it is difficult to provide sufficient hydrostatic pressure to prevent further leakage of cerebrospinal fluid, and if the thickness of the second repairing layer 2 is greater than 1-3 mm, the overall strength of the repairing material is too low.
In some embodiments of the present invention, after the lyophilization process, further comprising:
cross-linking treatment, water washing treatment and vacuum drying, wherein the cross-linking treatment comprises the step of soaking the freeze-dried material by using glutaraldehyde solution.
In this embodiment, the crosslinking treatment includes:
(1) Preparing a cross-linking agent solution: measuring absolute ethyl alcohol with a certain volume by using a measuring cylinder, transferring the absolute ethyl alcohol into a reaction kettle, transferring glutaraldehyde with a certain volume (the mass fraction of the glutaraldehyde is 50%) by using a liquid transfer gun, and preparing an absolute ethyl alcohol solution of glutaraldehyde with a certain concentration;
absolute ethyl alcohol (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) Soaking the freeze-dried material in the absolute ethanol solution of glutaraldehyde (the specific dosage is calculated according to an electronic plate feeding table), wherein the stirring speed of the reaction kettle is 20-30r/min, the material can rotate along with stirring, and the material is crosslinked for 48 hours.
In this embodiment, the water washing treatment includes:
(1) Taking out the cross-linked material from the cross-linking agent solution;
(2) The centrifuge was loaded with filter bags and centrifuged once (5 seconds); the rotating speed of the centrifugal machine is 3000r/min by default;
(3) Completely soaking the materials in a 3% hydrogen peroxide solution for 42 +/-1 h, wherein the soaking ratio is 1;
(4) Carrying out ultrasonic treatment on purified water for 30min, and centrifuging once (5 s) after ultrasonic treatment; repeating for 2 times;
(5) Carrying out ultrasonic treatment on the absolute ethyl alcohol for 5min, wherein the volume of the absolute ethyl alcohol is based on the principle of immersing the product, and carrying out centrifugal operation once (5 seconds) after the ultrasonic treatment is finished.
The vacuum drying comprises the following steps:
and (3) putting 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, an embodiment of the present invention further provides another method for preparing a children skull repairing material, including:
200, acquiring skull model data of a child patient, and obtaining a skull damage-shaped mould through 3D printing according to the skull model data;
step 202, 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 2.8-3.25%, 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, putting the layered titanium metal net 3 into the mold with the side of the mold facing the intracranial upwards, wherein the titanium metal net 3 has elasticity;
step 208, injecting the mixed solution into a mold to obtain a first repairing layer 1;
step 210, injecting a second collagen gel solution onto the first repairing layer 1, wherein the solid content of the second collagen gel solution is 1.5-2%, so as to obtain a second repairing layer 2;
and step 212, performing freeze-drying treatment, crosslinking treatment, washing treatment and vacuum drying to obtain the children skull repairing material.
In order to more clearly illustrate the technical scheme and advantages of the present invention, the following detailed description is provided for a method for preparing a skull repairing material through several embodiments.
Example 1
Obtaining skull model data of a child patient, and obtaining a skull damage shape mould 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 a mixed solution, wherein the mass ratio of collagen to the glycerol in the mixed solution is 100:10;
the side of the mould facing the intracranial part is upward, and a layered titanium metal net is placed into the mould and 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;
and (3) performing freeze-drying treatment, crosslinking treatment, washing treatment and vacuum drying to obtain the children skull repairing material.
Example 2
Obtaining skull model data of a child patient, and obtaining a skull damage shape mould 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 a mixed solution, wherein the mass ratio of collagen to the glycerol in the mixed solution is 100:12.5;
the side of the mould facing the intracranial part is upward, and a layered titanium metal net is placed into the mould and 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;
and (3) performing freeze-drying treatment, crosslinking treatment, washing treatment and vacuum drying to obtain the children skull repairing material.
Example 3
Obtaining skull model data of a child patient, and obtaining a skull damage shape mould 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 a solvent to the mixture;
adding glycerol into a mixed solution, wherein the mass ratio of collagen to the glycerol in the mixed solution is 100:15;
the side of the mould facing the intracranial part is upward, and a layered titanium metal net is placed into the mould and 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;
and (3) performing freeze-drying treatment, crosslinking treatment, washing treatment and vacuum drying to obtain the children skull repairing material.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present 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 solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.

Claims (10)

1. The preparation method of the children skull repairing material is characterized by comprising the following steps:
obtaining skull model data of a child patient, and obtaining a skull damage shape mould 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 intracranial, of the mold is upward, and the layered titanium metal net (3) is placed into the mold, wherein the titanium metal net (3) has elasticity;
injecting the mixed solution into a mold to obtain a first repairing layer (1);
and injecting a second collagen gel solution onto the first repairing layer (1) to obtain a second repairing layer (2), and performing freeze-drying treatment to obtain the children skull repairing material.
2. The method for producing according to claim 1, wherein the titanium metal mesh (3) comprises titanium strips (311) and connecting portions (32), the titanium strips (311) are connected end to end by rivets in a rotating manner to form zigzag-shaped titanium chains (31), the titanium chains (31) are expandable or contractible, and the connecting portions (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. A method as claimed in claim 2, wherein said connecting portion (32) comprises a connecting rod (321) coupled end-to-end in rotation.
4. The method of claim 1, wherein the first collagen gel solution has a solid content of 2.8 to 3.25%.
5. The method according to claim 1, wherein the mass ratio of the collagen to the mineralized collagen in the mixed solution is 100: (55-60).
6. The method according to claim 1, characterized by comprising, after said obtaining the mixed solution and before said injecting the mixed solution into a mold:
glycerol was added to the mixed solution.
7. The method according to claim 6, wherein the mass ratio of the collagen to the glycerin in the mixed solution is 100: (10-15).
8. The method according to claim 1, wherein the solid content of the second aqueous collagen gel solution is 1.5 to 2%.
9. The method according to claim 1, wherein the thickness of the second repair layer (2) is 1 to 3mm.
10. The method for preparing according to claim 1, further comprising, after the lyophilizing process:
and the crosslinking treatment comprises the steps of soaking the freeze-dried material by using a glutaraldehyde solution, and washing and vacuum drying.
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