CN108421088A - A kind of artificial bone renovating material of mineralized collagen base moderate strength and preparation method thereof - Google Patents
A kind of artificial bone renovating material of mineralized collagen base moderate strength and preparation method thereof Download PDFInfo
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- CN108421088A CN108421088A CN201810353944.5A CN201810353944A CN108421088A CN 108421088 A CN108421088 A CN 108421088A CN 201810353944 A CN201810353944 A CN 201810353944A CN 108421088 A CN108421088 A CN 108421088A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/48—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with macromolecular fillers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Abstract
The present invention relates to a kind of artificial bone renovating materials of mineralized collagen base moderate strength and preparation method thereof.This method includes preparing polymer/mineralized collagen composite material, prepare rigid polymer/mineralized collagen composite material granular and preparing the artificial bone renovating material of mineralized collagen base moderate strength.Using this method can obtain it is a kind of not only there is certain support strength, but also have the bone renovating material of certain porosity, the material can use at the position for needing certain load-bearing, such as tibial plateau, and Evans is with bone-culting operation, in Cotton wedge-like opening bone-culting operations.
Description
Technical field
The present invention relates to bone material technical field more particularly to a kind of artificial bone renovating materials of mineralized collagen base moderate strength
And preparation method thereof.
Background technology
Bone tissue is maximum as human body while being also to be easiest to cause the histoorgan of defect, has every year millions of
Bone tissue defect patient need be treated surgically.It is lost by the bone object official caused by osteoporosis, wound, tumour, infection
Or tissue defect, become one of the problem of puzzlement human health life.The operation of bone collection reconstruction is clinically generally gone through to come
Restore defect shape and function, bone collection have become be only second to blood transfusion the graft having the call, and have by
Year increased trend.
Currently, the implantation material for the treatment of bone defect is broadly divided into autologous bone, allograph bone, bone- xenograft, artificial bone etc..Self
Bone collection is the most method of current Clinical practice, but it is cost " being cured the wound with wound " that it, which is a kind of sacrifice health position bone tissue,
Treatment means, the areas Hui Duigonggu cause new damage, and autologous bone limited source.Homogeneous allogenic bone or bone xenograft are most
Pipe overcomes the defect of autologous bone transplanting " limited source and secondary insult ", but deposits immunological rejection after the transfer, also deposits
In pathophorous potential danger.Various existing for autologous bone, allograph bone and bone xenograft to overcome the problems, such as, people exert always
Power wishes to prepare ideal bone renovating material by manual method.
Artificial bone renovating material is divided into for non-degradable material and the good material of degradable biological compatibility, but at present
Degradable bone renovating material common intensity is relatively low, or without suitable aperture and porosity, is replaced to meet creeping for osteocyte
Generation, to achieve the purpose that bone uptake.
Mineralized collagen bone renovating material is a kind of good bone renovating material of biocompatibility, and mineralized collagen is bionical natural
The bionic bone repair material with hierarchical structure of osteocyte epimatrix design.Its micro-structure and the aspect of ingredient two all with naturally
Bone photo seemingly, there is good biocompatibility and self-bone grafting repair ability, is a kind of excellent bone renovating material, is disadvantageous in that
The intensity of mineralising ossein repair materials is relatively low (generally in 1~2Mpa), limits use scope.
Applicant develops a kind of artificial bone renovating material of mineralized collagen base previously, can be by mineralized collagen bone renovating material
Intensity be increased to 65~150MPa, can be used as load receiving part with the artificial bone renovating material of mineralized collagen base of this high intensity
The bone renovating material of position.But due to its hardness height, elasticity modulus is high, can not be suitable for tibial plateau, Evans with bone-culting operation,
In Cotton wedge-like opening bone-culting operations.Moreover, it is also relatively low using the porosity of bone renovating material made from this method, no
Growth suitable for osteocyte and creeping substitution.
Hereafter, applicant develops a kind of artificial bone renovating material of high porosity again, by the optimization to preparation process,
The porosity of bone renovating material can reach 95%.But it has been found that this method only simply by high molecular material and
Mineralized collagen is combined into bone renovating material, although bone renovating material also has certain intensity, intensity is generally relatively low, together
Sample can not be suitable for tibial plateau, Evans with bone-culting operation, Cotton wedge-like opening bone-culting operations.
Being badly in need of one kind in Clinical practice has certain support strength, there is certain porosity, the good bone of biocompatibility
Repair materials.
Invention content
(1) technical problems to be solved
In view of the above-mentioned problems, the present invention provides a kind of artificial bone renovating material of mineralized collagen base moderate strength and its preparations
Method.
(2) technical solution
In order to solve the above technical problem, the present invention provides following technical solutions：
A kind of preparation method of the artificial bone renovating material of mineralized collagen base moderate strength, the preparation method include：
(1) polymer/mineralized collagen composite material is prepared：High molecular polymer is dissolved in organic solvent, is configured to
The first high polymeric solution of a concentration of 0.05~0.15g/mL and the second high polymeric solution of a concentration of 0.08~0.20g/mL；
Mineralized collagen dry powder and the first high polymeric solution are mixed, the height in mineralized collagen dry powder and the first high polymeric solution
The mass ratio of Molecularly Imprinted Polymer is 1:3~3:1, it is configured to first polymer/mineralized collagen mixed solution；
First polymer/mineralized collagen mixed solution is subjected to frozen dried, obtains lyophilized products；
Remaining organic solvent in lyophilized products is removed by way of supersonic extraction, then lyophilized products are dried,
Obtain polymer/mineralized collagen composite material；
(2) rigid polymer/mineralized collagen composite material granular is prepared：Polymer/mineralized collagen composite material is crushed,
Material after crushing is sieved with 80 mesh sieve, component is prepared by being used as by the fine powder of sieve；
Fine powder is carried out to first pressing, high pressure, double pressures and pressurize successively, obtains molded product；
Molded product is cleaned by ultrasonic and is dried, is then comminuted into fine grained, then by screening choose grain size be 0.1~
The fine grained of 0.8mm, as rigid polymer/mineralized collagen composite material granular；
(3) the artificial bone renovating material of mineralized collagen base moderate strength is prepared：By the second high polymeric solution and rigid polymer/
Mineralized collagen composite material granular is according to 2:1~4:3 mass ratio mixing, fills mould by obtained mixture, obtains under normal pressure
Precast body；
Precast body is subjected to frozen dried, remaining organic solvent in lyophilized products is removed by way of supersonic extraction,
Then vacuum drying again sterilizes to product by the way of irradiation, the artificial Bone Defect Repari of mineralized collagen base moderate strength is made
Material.
Preferably, in step (1), the high molecular polymer is selected from poly- ε-that viscosity is 1.0~3.0dl/g in oneself
Appointing in polylactic acid that ester, molecular weight are 100,000~300,000, the Poly(D,L-lactide-co-glycolide that molecular weight is 100,000~300,000
It is a kind of.
Preferably, in step (1), the organic solvent is selected from Isosorbide-5-Nitrae-dioxane, chloroform, chloroform, acetone, two
Any one of methyl sulfoxide or two kinds of mixed solvent.
Preferably, in step (1), the frozen dried is carried out as follows：By first polymer/mineralized collagen
Mixed solution first carries out pre-freeze under conditions of normal pressure, -30~-20 DEG C, then is risen under conditions of vacuum, -10~0 DEG C
China is finally dried in vacuo at 0~50 DEG C.
Preferably, in step (2), the first pressing, high pressure, double pressures and pressurize are carried out successively as follows：
First pressing：Fine powder is fitted into mold and is compacted, mold is placed on forcing press, manual pressure, until can not add
Power；
High pressure：Motor is started or with Manual pressure bar, until pressure reaches 15~25MPa；
Double pressures：Turnover mould lays down pedestal, carries out Bidirectional-pressure；
Pressurize：After the completion of double pressures, 90~120s of pressure is kept.
Preferably, in step (3), frozen dried is carried out to the precast body as follows：By the precast body
Pre-freeze is first carried out under conditions of normal pressure, -30~-20 DEG C, then is distilled under conditions of vacuum, -10~0 DEG C, finally 0
It is dried in vacuo at~50 DEG C.
Preferably, in step (3), the reagent used in the irradiation is Co 60 bactericidal agent, and dosage is 15~38kGy.
Preferably, in step (3), the shape of the precast body is graininess, square, cuboid, cylindric, trapezoidal
Any one of block, wedge block.
Preferably, the mineralized collagen dry powder is prepared with the following method：
S1, collagen is dissolved in any one of hydrochloric acid, citric acid or acetic acid, is configured to a concentration of 0.5~2mg/mL's
Collagen acid solution；
S2, the collagen acid solution is persistently stirred, the solution of calcium ions is slowly added dropwise, the addition of calcium ion is every gram of glue
Original is corresponding to be added 0.01~0.16mol of calcium ion；
S3, S2 acquired solutions are persistently stirred, are slowly added dropwise the solution of phosphorus-containing acid ion, the addition of phosphate anion with
The molar ratio of calcium ion addition is Ca/P=1.3~2.0；
S4, S3 acquired solutions are persistently stirred, NaOH solution is slowly added dropwise to mixed system pH to 6~8, as pH to 5~6
When, mixed system starts to precipitate, and as pH to 7, white suspension occurs in mixed system；
S5, mixed system obtained by S4 is stood 24~120 hours, isolates and precipitate and wash away foreign ion, then carries out
Freeze-drying, obtains the mineralized collagen dry powder after grinding.
A kind of artificial bone renovating material of mineralized collagen base moderate strength is made, it is preferable that described using above-mentioned preparation method
Repair materials have following feature：
Shape is any one of graininess, square, cuboid, cylindric, trapezoid block, wedge block；
Compression strength is between 8~50MPa；
Porosity is between 40~80%；
Degradation time is between 6~24 months.
(3) advantageous effect
The above-mentioned technical proposal of the present invention has the following advantages that：
There is the good high molecular material of a certain proportion of biocompatibility in bone renovating material, branch is provided for bone implantation
Frame, while having certain porosity again so that material disclosure satisfy that growing into for cell, by thin while having some strength
The creeping substitution of born of the same parents so that material is gradually degraded, while new bone being induced to gradually form.
The intensity of material can reach 8 to 50MPa, and porosity is 40% to 80%, and degradation time was at six months to 2 years.
Therefore, not only there is certain support strength the present invention provides a kind of, but also has the bone renovating material of certain porosity, the material can
So that used in the position for needing certain load-bearing, such as tibial plateau, Evans is with bone-culting operation, Cotton wedge-like opening bone-culting operations
In.
The bone renovating material of respective shapes can be designed according to indication using preparation method provided by the invention, such as can
To design wedge block, trapezoid block, bulky grain, little particle, the dentation either above-mentioned shape etc. with mounting hole.
The present invention is by first preparing mineralized collagen dry powder, then prepares mineralized collagen high polymer composite material, prepares hard mineralising
Collagen high polymer particle, it is quickly that hard mineralized collagen high polymer particle bonding is compound by high polymeric solution, it is prepared for one
The bone renovating material of kind moderate strength.
Description of the drawings
Fig. 1 is the flow diagram for the preparation method that embodiment 1 provides；
Fig. 2 is the structure chart that the bone renovating material that shape is trapezoid block is made in embodiment 1, and wherein a is stereogram, and b is to bow
View；
Fig. 3 is the structure chart that the bone renovating material that shape is wedge block is made in embodiment 2, and wherein a is left view, and b is just
View, c are vertical view, and d is stereogram；
Fig. 4 is the structure chart that the bone renovating material that shape is wedge block is made in embodiment 3, and wherein a is left view, and b is just
View, c are vertical view, and d is stereogram；
Fig. 5 is the three-dimensional structure diagram that the bone renovating material that shape is cylinder is made in embodiment 4；
Fig. 6 is the three-dimensional structure diagram that embodiment 5 is made that shape is cubical bone renovating material.
Specific implementation mode
To make the object, technical solutions and advantages of the present invention clearer, below in conjunction with the embodiment of the present invention, to this hair
Bright technical solution is clearly and completely described.Obviously, described embodiment is a part of the embodiment of the present invention, and
The embodiment being not all of.Based on the embodiments of the present invention, those of ordinary skill in the art are not making creative work
Under the premise of the every other embodiment that is obtained, shall fall within the protection scope of the present invention.
The present invention provides a kind of preparation method of the artificial bone renovating material of mineralized collagen base moderate strength, the preparation sides
Method includes：
(1) polymer/mineralized collagen composite material is prepared
High molecular polymer is dissolved in organic solvent, is configured to a concentration of 0.05~0.15g/mL (for example, can have
Body is 0.05g/mL, 0.08g/mL, 0.10g/mL, 0.12g/mL or 0.15g/mL) the first high polymeric solution and a concentration of
The second of 0.08~0.20g/mL (for example, can be specially 0.08g/mL, 0.10g/mL, 0.15g/mL or 0.20g/mL) is high poly-
Object solution.It is 100,000 that high molecular polymer used, which can be selected from the poly-epsilon-caprolactone, molecular weight that viscosity is 1.0~3.0dl/g,
~30 ten thousand polylactic acid, any one of the Poly(D,L-lactide-co-glycolide that molecular weight is 100,000~300,000.First high polymer
Solution and the second high polymeric solution can select identical high polymer or polymeric compositions to be prepared, and can also select difference
High polymer or polymeric compositions prepared.Organic solvent can be selected from 1,4- dioxane, chloroform, chloroform, third
Any one of ketone, dimethyl sulfoxide (DMSO) or two kinds of mixed solvent.
Mineralized collagen dry powder and the first high polymeric solution are mixed, the height in mineralized collagen dry powder and the first high polymeric solution
The mass ratio of Molecularly Imprinted Polymer is 1:3~3:1 (for example, can be specially 1:3、1:2、1:1、2:1 or 3:1), it is configured to first
Polymer/mineralized collagen mixed solution.
Mineralized collagen dry powder used in the step can be prepared as follows：
S1, collagen is dissolved in any one of hydrochloric acid, citric acid or acetic acid, is configured to a concentration of 0.5~2mg/mL (examples
Such as, can be specially 0.5mg/mL, 1.0mg/mL, 1.5mg/mL, 2mg/mL) collagen acid solution；
S2, the collagen acid solution is persistently stirred, the solution of calcium ions is slowly added dropwise, the addition of calcium ion is every gram of glue
Original is corresponding be added 0.01~0.16mol of calcium ion (for example, can be specially 0.01mol, 0.05mol, 0.08mol, 0.1mol,
0.12mol, 0.15mol or 0.16mol)；
S3, S2 acquired solutions are persistently stirred, are slowly added dropwise the solution of phosphorus-containing acid ion, the addition of phosphate anion with
The molar ratio of calcium ion addition is Ca/P=1.3~2.0 (for example, can be specially 1.3,1.5,1.6,1.7,1.9,2.0)；
S4, S3 acquired solutions are persistently stirred, NaOH solution is slowly added dropwise to mixed system pH to 6~8, as pH to 5~6
When, mixed system starts to precipitate, and as pH to 7, white suspension occurs in mixed system；
S5, mixed system obtained by S4 is stood 24~120 hours, isolates and precipitate and wash away foreign ion, then carries out
Freeze-drying, obtains the mineralized collagen dry powder after grinding.
First polymer/mineralized collagen mixed solution is subjected to frozen dried, obtains lyophilized products.
Freeze-drying can carry out as follows：By first polymer/mineralized collagen mixed solution first normal pressure, -30~-
Pre-freeze is carried out under conditions of 20 DEG C (for example, can be specially -30 DEG C, -25 DEG C, -20 DEG C), then in vacuum, -10~0 DEG C of (example
Such as, can be specially -10 DEG C, -5 DEG C, 0 DEG C) under conditions of distil, finally at 0~50 DEG C (for example, can be specially 0
DEG C, 5 DEG C, 10 DEG C 15 DEG C, 20 DEG C, 30 DEG C, 40 DEG C, 50 DEG C) under be dried in vacuo.
Remaining organic solvent in lyophilized products is removed by way of supersonic extraction, then lyophilized products are dried,
Obtain polymer/mineralized collagen composite material；
(2) rigid polymer/mineralized collagen composite material granular is prepared
Polymer/mineralized collagen composite material is crushed, the material after crushing is sieved with 80 mesh sieve, will be passed through
The fine powder of sieve is as preparation component.
Fine powder is carried out to first pressing, high pressure, double pressures and pressurize successively, obtains molded product.
Carry out the first pressing, high pressure, double pressures and pressurize successively as follows：
First pressing：Fine powder is fitted into mold and is compacted, mold is placed on forcing press, manual pressure, until can not add
Power；
High pressure：Start motor or with Manual pressure bar, until pressure reach 15~25MPa (for example, can be specially 15MPa,
20MPa、25MPa)；
Double pressures：Turnover mould lays down pedestal, carries out Bidirectional-pressure；
Pressurize：After the completion of double pressures, 90~120s of pressure (can be specially 90s, 100s, 110s, 120s) is kept.
Molded product is cleaned by ultrasonic and is dried, is then comminuted into fine grained, then by screening choose grain size be 0.1~
The fine grained of 0.8mm, as rigid polymer/mineralized collagen composite material granular；
(3) the artificial bone renovating material of mineralized collagen base moderate strength is prepared
By the second high polymeric solution and rigid polymer/mineralized collagen composite material granular according to 2:1~4:3 (for example, can
To be specially 2:1、3:2、4:3) mass ratio mixing, fills mould by obtained mixture, can be set according to indication under normal pressure
The mold of respective shapes is counted, satisfactory precast body is made.The shape of the precast body can be designed to graininess, pros
Any one of body, cuboid, cylindric, trapezoid block, wedge block.
Precast body is subjected to frozen dried, remaining organic solvent in lyophilized products is removed by way of supersonic extraction,
Then vacuum drying again sterilizes to product by the way of irradiation, the artificial Bone Defect Repari of mineralized collagen base moderate strength is made
Material.In this step, can frozen dried be carried out to the precast body as follows：By the precast body first normal
Pre-freeze is carried out under conditions of pressure, -30~-20 DEG C (for example, can be specially -30 DEG C, -25 DEG C, -20 DEG C), then in vacuum, -10
~0 DEG C for example, can be specially -10 DEG C, -5 DEG C, 0 DEG C) under conditions of distil, finally at 0~50 DEG C for example, can have
Body be 0 DEG C, 5 DEG C, 10 DEG C, 15 DEG C, 20 DEG C, 30 DEG C, 40 DEG C, 50 DEG C) under be dried in vacuo.Co 60 may be used in the irradiation
Bactericidal agent, dosage are 15~38kGy.
The present invention provides a kind of artificial bone renovating materials of mineralized collagen base moderate strength, using above-mentioned preparation method system
.Preferably, the repair materials have following feature：
Shape is any one of graininess, square, cuboid, cylindric, trapezoid block, wedge block；
Compression strength is between 8~50MPa；
Porosity is between 40~80%；
Degradation time is between 6~24 months.
It is the embodiment that the present invention enumerates below.
Embodiment 1
As shown in Figure 1, preparation method includes the following steps：
The preparation of step 1, mineralized collagen dry powder, specifically includes：
S1, collagen is dissolved in hydrochloric acid, is configured to the acid solution of collagen, wherein collagen concentration is 0.5mg/mL；
S2, continue whipping step S1 acquired solutions, the solution of calcium ions is slowly added dropwise, the addition of calcium ion is every gram
Collagen, which corresponds to, is added calcium ion 0.01mol；
S3, S2 acquired solutions are persistently stirred, are slowly added dropwise the solution of phosphorus-containing acid ion, the addition of phosphate anion with
The molar ratio of calcium ion addition is Ca/P=1.5 in step S2；
S4, continue whipping step S3 acquired solutions, NaOH solution is slowly added dropwise to mixed system pH=6~8, works as pH=5
When~6, mixed system starts to precipitate, and as pH=7, white suspension occurs in mixed system；
S5, mixed system obtained by step S4 is stood 24 hours, isolates and precipitate and wash away foreign ion, then carries out cold
Be lyophilized it is dry, after grinding obtain mineralized collagen material dry powder it is spare.
The preparation of step 2, polymer/mineralized collagen composite material, specifically includes：
It is swollen process：It is molten by high molecular polymer (the present embodiment selection is poly-epsilon-caprolactone, viscosity 1.8dl/g)
Solution forms No. 1 high polymeric solution, a concentration of 0.05g/mL in Isosorbide-5-Nitrae-dioxane；
Mineralized collagen dry powder is added into No. 1 high polymeric solution, polymer/mineralized collagen mixed solution, the mine is made
The mass ratio for changing collagen dry powder and the high molecular polymer is 1:2；
Polymer/mineralized collagen mixed solution is subjected to pre-freeze in -20 DEG C under normal pressure, then under vacuum in 0 DEG C
It distils, then is dried in vacuo at 50 DEG C；
Remaining organic solvent and drying after being lyophilized are removed by way of supersonic extraction, thus the obtained polymer/
Mineralized collagen composite material.
The preparation of step 3, rigid polymer/mineralized collagen composite material granular, specifically includes：
It is placed in polymer obtained above/mineralized collagen composite material in micromill, crushes 5-10 seconds, obtain
Tiny powder；With the stainless steel screening polymer through crushing/mineralized collagen composite material material, the mesh number of stainless steel sieve is
(respective material grain diameter is 80 mesh<200 μm), it is the required powder for carrying out next step by the powder that stainless steel sieves.
Mould pressing process：Powder is fitted by funnel in the cylindrical type mold of Φ 25mm, stainless steel column is used in combination to be compacted；Just
Process is pressed, charged mold is placed on forcing press, manual pressure, until hand cannot reinforce；High pressure procedure starts electricity
Machine (or with Manual pressure bar), until reaching the 25.0MPa pressure of setting；Double pressure processes, gauge hand reach predetermined high pressure value
Afterwards, it shuts down, turnover mould or lays down pedestal, carry out Bidirectional-pressure；Pressurize process after the completion of double pressures, carries out keeping pressure 90 seconds；
It is demoulded after pressurize, the simple cleaning appropriate for carrying out surface after being cleaned by ultrasonic and drying, material is placed in small
In type pulverizer, crushes 3~5 times, 1~3 second every time, obtain fine grained；Sieving and casing is sieved with stainless steel bushing screen through crushing
Material chooses the particle that grain size is 0.1~0.8mm.The rigid polymer of the as described preparation/mineralized collagen composite material
Grain.
The preparation of step 4, the artificial bone renovating material of moderate strength mineralized collagen base, specifically includes：
Prepare No. 2 high polymeric solutions：By polymer (the present embodiment select be poly-epsilon-caprolactone, viscosity 1.8dl/g),
It is dissolved in Isosorbide-5-Nitrae-dioxane, is configured to No. 2 high polymeric solutions of a concentration of 0.08g/mL.
Above-mentioned No. 2 high polymeric solutions are stirred rapidly with rigid polymer/mineralized collagen composite material granular, liquid powder
Mixed proportion is mass ratio 2:1,
It fills mould under normal pressure, is prepared into required shape (material manufactured in the present embodiment is trapezoid block, as shown in Figure 2).
The good product of mould will be filled and carry out pre-freeze at -20 DEG C, then distilled under vacuum in 0 DEG C, then 50 DEG C into
Row vacuum drying；Remaining organic solvent in lyophilized products is removed by way of supersonic extraction, is dried in vacuo；
Demoulding trimming, irradiation sterilization (Co 60 bactericidal agent, dosage 15-38kGy) are moderate strength mineralized collagen base afterwards
Artificial bone renovating material.
After testing, the intensity of the bone renovating material is 32MPa, porosity 55%.
Embodiment 2
It is substantially the same that the preparation method is the same as that of Example 1, the difference is that：
Molecular weight is used to prepare No. 1 high polymeric solution, mass-volume concentration 0.15g/mL for 100,000 polylactic acid；
Mineralized collagen dry powder and No. 1 high polymeric solution are according to 1:1 mass ratio mixing；
Molecular weight is used to be configured to No. 2 high polymeric solutions of a concentration of 0.20g/mL for 300,000 polylactic acid；
No. 2 high polymeric solutions are mass ratio 4 with rigid polymer/mineralized collagen composite material granular mixed proportion:3.
The shape of final bone renovating material obtained is wedge block, as shown in Figure 3.
Different models can be made as needed, the concrete condition of each model is as shown in the table.
After testing, the intensity of the bone renovating material is 38MPa, porosity 45%.
Embodiment 3
It is substantially the same that the preparation method is the same as that of Example 1, the difference is that：
Molecular weight is used to prepare No. 1 high polymeric solution, mass-volume concentration for 100,000 Poly(D,L-lactide-co-glycolide
For 0.1g/mL；
Mineralized collagen dry powder and No. 1 high polymeric solution are according to 3:1 mass ratio mixing；
No. 2 high polymeric solutions of a concentration of 0.15g/mL are configured to using the poly-epsilon-caprolactone of viscosity 2.0dl/g；
No. 2 high polymeric solutions are mass ratio 4 with rigid polymer/mineralized collagen composite material granular mixed proportion:2.5.
The shape of final bone renovating material obtained is wedge block, as shown in Figure 4.
Different models can be made as needed, the concrete condition of each model is as shown in the table.
After testing, the intensity of the bone renovating material is 22MPa, porosity 65%.
Embodiment 4
It is substantially the same that the preparation method is the same as that of Example 1, the difference is that：
Molecular weight is used to prepare No. 1 high polymeric solution, mass-volume concentration for 300,000 Poly(D,L-lactide-co-glycolide
For 0.15g/mL；
Mineralized collagen dry powder and No. 1 high polymeric solution are according to 2:1 mass ratio mixing；
Use No. 2 height that molecular weight is configured to a concentration of 0.20g/mL for 300,000 Poly(D,L-lactide-co-glycolide poly-
Object solution；
No. 2 high polymeric solutions are mass ratio 1.5 with rigid polymer/mineralized collagen composite material granular mixed proportion:1.
The shape of final bone renovating material obtained is cylinder, as shown in Figure 5.
After testing, the intensity of the bone renovating material is 25MPa, porosity 60%.
Embodiment 5
It is substantially the same that the preparation method is the same as that of Example 1, the difference is that：
Molecular weight is used to prepare No. 1 high polymeric solution, a concentration of 0.1g/mL for 300,000 polylactic acid；
Mineralized collagen dry powder and No. 1 high polymeric solution are according to 1:2 mass ratio mixing；
Molecular weight is used to prepare No. 2 high polymeric solutions, a concentration of 0.1g/mL for 200,000 polylactic acid；
No. 2 high polymeric solutions are mass ratio 4 with rigid polymer/mineralized collagen composite material granular mixed proportion:3.
The shape of final bone renovating material obtained is cube, as shown in Figure 6.
After testing, the intensity of the bone renovating material is 18MPa, porosity 75%.
Embodiment 6
It is substantially the same that the preparation method is the same as that of Example 1, the difference is that：
In step 4, the mass ratio of No. 2 high polymeric solutions and rigid polymer/mineralized collagen composite material granular is 3:2.
After testing, the intensity of repair materials obtained is 35MPa, porosity 52%, than the intensity of the product of embodiment 1
It is higher, but porosity decreases.
Comparative example 1
It is substantially the same that the preparation method is the same as that of Example 1, the difference is that：
In step 3, by crushing and sieving, the size controlling of rigid polymer/mineralized collagen composite material granular is existed
0.1mm or less (not including 0.1mm).It can not play the role of grit since grain size is too small, there is mixing in preparation process
It is unable to complete wetting, institute's prepared material dissipates defeated and dispersed situation.
Comparative example 2
It is substantially the same that the preparation method is the same as that of Example 1, the difference is that：
In step 4, the mass ratio of organic solvent and high molecular polymer in No. 2 high polymeric solutions is 1:1.Experiment is lost
It loses, high polymer cannot be completely dissolved.
Comparative example 3
It is substantially the same that the preparation method is the same as that of Example 1, the difference is that：
In step 4, the mass ratio of organic solvent and high molecular polymer in No. 2 high polymeric solutions is 15:1.
After testing, the intensity of contrast sample 5 obtained is 3MPa, porosity 82%.
Comparative example 4
It is substantially the same that the preparation method is the same as that of Example 1, the difference is that：
The preparation of step 1, mineralized collagen dry powder, specifically includes：
S1, collagen is dissolved in hydrochloric acid, is configured to the acid solution of collagen, wherein collagen concentration is 0.05mg/mL.Due to glue
Original content is too low so that and the yield of mineralized collagen dry powder is low, and energy consumption is big, deposited phenomenon unobvious, even if material can be prepared,
Efficiency is too low in actual production, time-consuming and laborious.
In conclusion not only there is certain support strength the present invention provides a kind of, but also there is the Bone Defect Repari material of certain porosity
Material and preparation method thereof, the material can use at the position for needing certain load-bearing, and such as tibial plateau, Evans is with osteotomy hand
Art, in Cotton wedge-like opening bone-culting operations.
Finally it should be noted that：The above embodiments are merely illustrative of the technical solutions of the present invention, rather than its limitations；Although
Present invention has been described in detail with reference to the aforementioned embodiments, it will be understood by those of ordinary skill in the art that：It still may be used
With technical scheme described in the above embodiments is modified or equivalent replacement of some of the technical features；
And these modifications or replacements, various embodiments of the present invention technical solution that it does not separate the essence of the corresponding technical solution spirit and
Range.
Claims (10)
1. a kind of preparation method of the artificial bone renovating material of mineralized collagen base moderate strength, which is characterized in that the preparation method
Including：
(1) polymer/mineralized collagen composite material is prepared：High molecular polymer is dissolved in organic solvent, concentration is configured to
For the first high polymeric solution of 0.05~0.15g/mL and the second high polymeric solution of a concentration of 0.08~0.20g/mL；
Mineralized collagen dry powder and the first high polymeric solution are mixed, the macromolecule in mineralized collagen dry powder and the first high polymeric solution
The mass ratio of polymer is 1:3~3:1, it is configured to first polymer/mineralized collagen mixed solution；
First polymer/mineralized collagen mixed solution is subjected to frozen dried, obtains lyophilized products；
Remaining organic solvent in lyophilized products is removed by way of supersonic extraction, then lyophilized products are dried, and is obtained
Polymer/mineralized collagen composite material；
(2) rigid polymer/mineralized collagen composite material granular is prepared：Polymer/mineralized collagen composite material is crushed, by powder
Material after broken is sieved with 80 mesh sieve, and component is prepared by being used as by the fine powder of sieve；
Fine powder is carried out to first pressing, high pressure, double pressures and pressurize successively, obtains molded product；
Molded product is cleaned by ultrasonic and is dried, is then comminuted into fine grained, then it is 0.1~0.8mm to choose grain size by screening
Fine grained, as rigid polymer/mineralized collagen composite material granular；
(3) the artificial bone renovating material of mineralized collagen base moderate strength is prepared：By the second high polymeric solution and rigid polymer/mineralising
Collagen composite materials particle is according to 2:1~4:3 mass ratio mixing, fills mould by obtained mixture, obtains prefabricated under normal pressure
Body；
Precast body is subjected to frozen dried, remaining organic solvent, vacuum in lyophilized products are removed by way of supersonic extraction
It is dry, it is then sterilized again to product by the way of irradiation, the artificial bone renovating material of mineralized collagen base moderate strength is made.
2. preparation method according to claim 1, which is characterized in that in step (1), the high molecular polymer is selected from
Poly-epsilon-caprolactone that viscosity is 1.0~3.0dl/g, the polylactic acid that molecular weight is 100,000~300,000, molecular weight are 100,000~300,000
Any one of Poly(D,L-lactide-co-glycolide.
3. preparation method according to claim 1, which is characterized in that in step (1), the organic solvent is selected from Isosorbide-5-Nitrae-
Any one of dioxane, chloroform, chloroform, acetone, dimethyl sulfoxide (DMSO) or two kinds of mixed solvent.
4. preparation method according to claim 1, which is characterized in that in step (1), as follows described in progress
Frozen dried：First polymer/mineralized collagen mixed solution is first subjected to pre-freeze under conditions of normal pressure, -30~-20 DEG C, then
It distils under conditions of vacuum, -10~0 DEG C, is finally dried in vacuo at 0~50 DEG C.
5. preparation method according to claim 1, which is characterized in that in step (2), carry out successively as follows
The first pressing, high pressure, double pressures and pressurize：
First pressing：Fine powder is fitted into mold and is compacted, mold is placed on forcing press, manual pressure, until can not reinforce；
High pressure：Motor is started or with Manual pressure bar, until pressure reaches 15~25MPa；
Double pressures：Turnover mould lays down pedestal, carries out Bidirectional-pressure；
Pressurize：After the completion of double pressures, 90~120s of pressure is kept.
6. preparation method according to claim 1, which is characterized in that in step (3), as follows to described pre-
Body processed carries out frozen dried：The precast body is first subjected to pre-freeze under conditions of normal pressure, -30~-20 DEG C, then in vacuum, -10
It distils under conditions of~0 DEG C, is finally dried in vacuo at 0~50 DEG C.
7. preparation method according to claim 1, which is characterized in that in step (3), the reagent used in the irradiation is
Co 60 bactericidal agent, dosage are 15~38kGy.
8. preparation method according to claim 1, which is characterized in that in step (3), the shape of the precast body is
Any one of granular, square, cuboid, cylindric, trapezoid block, wedge block.
9. according to claim 1 to 8 any one of them preparation method, which is characterized in that the mineralized collagen dry powder is using such as
It is prepared by lower method：
S1, collagen is dissolved in any one of hydrochloric acid, citric acid or acetic acid, is configured to the collagen of a concentration of 0.5~2mg/mL
Acid solution；
S2, the collagen acid solution is persistently stirred, the solution of calcium ions is slowly added dropwise, the addition of calcium ion is every gram of collagen pair
0.01~0.16mol of calcium ion should be added；
S3, S2 acquired solutions are persistently stirred, are slowly added dropwise the solution of phosphorus-containing acid ion, the addition of phosphate anion and calcium from
The molar ratio of sub- addition is Ca/P=1.3~2.0；
S4, S3 acquired solutions are persistently stirred, NaOH solution is slowly added dropwise to mixed system pH to 6~8, as pH to 5~6, mixes
Zoarium system starts to precipitate, and as pH to 7, white suspension occurs in mixed system；
S5, mixed system obtained by S4 is stood 24~120 hours, isolates and precipitate and wash away foreign ion, is then freezed
It is dry, the mineralized collagen dry powder is obtained after grinding.
10. a kind of artificial bone renovating material of mineralized collagen base moderate strength, which is characterized in that using any one of claim 1 to 9
The preparation method is made, it is preferable that the repair materials have following feature：
Shape is any one of graininess, square, cuboid, cylindric, trapezoid block, wedge block；
Compression strength is between 8~50MPa；
Porosity is between 40~80%；
Degradation time is between 6~24 months.
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