CN110038164A - Biologically active inorganic bone holder material of one kind and preparation method thereof - Google Patents
Biologically active inorganic bone holder material of one kind and preparation method thereof Download PDFInfo
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- CN110038164A CN110038164A CN201910393012.8A CN201910393012A CN110038164A CN 110038164 A CN110038164 A CN 110038164A CN 201910393012 A CN201910393012 A CN 201910393012A CN 110038164 A CN110038164 A CN 110038164A
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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
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
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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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
- A61L27/3645—Connective tissue
- A61L27/365—Bones
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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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
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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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3691—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/112—Phosphorus-containing compounds, e.g. phosphates, phosphonates
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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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 technical field of biological materials, and in particular to biologically active inorganic bone holder material of one kind and preparation method thereof.It is calcined by the natural biological bone material at a certain temperature to inorganic material and with active inorganic material, while so that the biocompatibility of natural bone material is retained, guarantee the safety of finished product, the risk of immunological rejection and transmission after excluding implantation host.And it is more advantageous to the combination of inorganic material and natural biological bone material, it can preferably retain the property of inorganic active material, be further ensured that the mechanical strength of bone holder material.Preferable effect is presented in various aspects such as biocompatibility, mechanical strength, osteoinductive and safeties in the inorganic bone holder material being prepared by the method for the invention, is conducive to it in the popularization and application in bone defect healing field.
Description
Technical field
The present invention relates to technical field of biological materials, and in particular to a kind of biologically active inorganic bone holder material and
Preparation method.
Background technique
The defect as caused by wound or disease is clinically very common, not only seriously affects the quality of the life of patient, and
And heavy financial burden is brought to them.However, repairing always surgery to it since bone itself repair ability is limited and facing
A problem on bed, there is no the treatment method of special efficacy so far.Currently, self/allogenic bone transplantation, periosteum is clinically mostly used to move
The restorative procedures such as plant, osteocyte transplanting, micro fractures.But that there are donor sources is limited for they, repaired area is small, immunological rejection, shifting
The deficiencies of cell is lost or is resistant to stress difference place is planted, repairing effect is bad.And organizational engineering developed in recent years, it is
The reparative regeneration of bone defect provides new thought.
Ideal tissue scaffold design material aperture is close with normal bone size, and good microenvironment can be provided for cell,
It can be used safely in human body；With good osteoconductive, and there is inducing bone mesenchymal stem cell to osteoblast to break up and promote
Into the potential of its proliferation；It can be processed to required shape, and there is good mechanical strength, make its one after implanting
Its shape can be still kept in fixing time.
In order to guarantee that above-mentioned obtained tissue scaffold design material has above-mentioned desired characteristics, this field has attempted largely to grind
Study carefully.As disclosed a kind of preparation process of biological support with structural features of natural bones in CN1759816A, pass through preparation
Template bone, casting/grouting, removal template bone are prepared, and prepared biologic bracket material has the structure feature of nature bone.
There is higher mechanical strength, porosity and more intercommunicating pores than the biologic bracket material obtained by conventional method.But
It has a disadvantage in that and is only added to macromolecule component in the three-dimensional structure of natural biological bone, on the one hand lack and effectively promote bone again
Raw active constituent, while the problems such as do not effectively remove the ingredients such as the collagen in bone holder material, be also easy to produce immunological rejection.
A kind of degradable more empty compound support frame materials of bone collection are disclosed in CN105597158A, by calcining with ox
Grafting Cancellous Bone Bolt mine porous support carries out hydro-thermal reaction as entirely or essentially calcium source, with sulphur source-phosphorus source composite solution, forms sulfuric acid
Calcium-hydroxyapatite or calcium sulfate-two series composite materials of calcium monohydrogen phosphate-hydroxyapatite.It is porous that the technology remains bone mine
Three-dimensional structure, and the method by impregnating introduces the inorganic mineral constituents such as calcium sulfate, calcium monohydrogen phosphate and hydroxyapatite thereto,
But disadvantage is since using the prolonged method for calcinating of high temperature (900-1200 DEG C, calcine 8-12h), its mechanical strength is poor, and
The ingredient of introducing is clinically conventional use of inorganic mineral filling material of bone, and osteogenic activity is poor, do not have preferably at
Bone inductive effect.
Summary of the invention
In order to solve the above-mentioned technical problems, the present invention provides a kind of 3 D stereo knots with natural biological bone material
Structure can promote knitting, mechanical strength big and safe inorganic bone holder material and preparation method thereof.
An object of the present disclosure is to provide a kind of preparation method of biologically active inorganic bone holder material, including
Following steps:
(1) inorganic material is calcined at 1100-1300 DEG C, obtains active inorganic material；
(2) the active inorganic material is mixed with natural biological bone material, is obtained with the natural of active inorganic material
Biological bone material；
(3) the natural biological bone material with active inorganic material is calcined at 400-1000 DEG C.
Natural biological bone material in the present invention can be selected from ox bone, pig bone, people's bone etc..Structure include blocky, graininess or
Powdery etc..
It is a discovery of the invention that activity can be made it have by calcining inorganic material at 1100-1300 DEG C, with it is natural
There is better adhesive force when biological bone material combines.In step (3), if temperature is lower than 400 DEG C, it is easy to appear combination
Loosely the problem of, is easy to influence the activity of inorganic material, so that it is lost mechanical strength, and then make if temperature is higher than 1000 DEG C
It is powdered to obtain final material presentation；Only when calcination temperature is in 400-1000 DEG C, active inorganic material can be reinforced well
Combination between material and natural biological bone material, to be more advantageous to the shape for keeping inorganic bone holder material, and improves its machine
Tool intensity；And it can be effectively retained biocompatibility brought by natural biological bone material, may advantageously facilitate material obtained carefully
Intracellular growth and creeping substitution, and may advantageously facilitate osteogenic growth and knitting；It can remove in natural biological bone material simultaneously
The organic matters such as collagen, prion exclude the wind because of immunological rejection and transmission after implantation host caused by its use
Danger.
Preferably, the inorganic material is calcined at 1150-1250 DEG C.
Preferably, the natural biological bone material with active inorganic material is calcined at 750-950 DEG C.
Preferably, the calcination time of the active inorganic material is 8~12h；Preferably 10h.
Preferably, the calcination time of the natural biological bone material with active inorganic material is 10-120min；It is excellent
It is selected as 20-60min.
Preferably, the inorganic material includes following parts by weight of component: SiO215-50 parts, Na2CO315-50 parts,
CaCO310-40 parts, MgCO35-35 parts, P2O55-20 parts.
The more preferably described inorganic material includes following parts by weight of component: SiO220-40 parts, Na2CO320-40 parts,
CaCO315-30 parts, MgCO35-15 parts, P2O510-15 parts.
When inorganic material includes said components, active inorganic material obtained is more advantageous to after calcining and activating
Promote osteogenic growth, material is made to have effects that preferably to promote knitting.
Preferably, the weight ratio of the active inorganic material and the natural biological bone material is 1:1-30.
Preferably, the active inorganic material is mixed with the natural biological bone material by ultrasonic vibration；It is preferred that mixed
The conjunction time is 15-60min.
Preferably, the partial size of the active inorganic material is within 45 microns.
Preferably, the described method comprises the following steps:
S1, natural biological bone material is taken, after removing organic matter, is impregnated and be cleaned by ultrasonic with surfactant solution, it is then pure
Change water to rinse well；
S2, the inorganic material after calcining pretreatment, is obtained active inorganic material and be ground at 1100-1300 DEG C
Its partial size is within 45 microns；
S3, the natural biological bone material Jing Guo S1 step and the active inorganic material ultrasonic vibration Jing Guo S2 step are mixed
15-60min obtains the natural biological bone material with active inorganic material；
S4, the resulting natural biological bone material with active inorganic material of S3 step is calcined at 400-1000 DEG C,
And it is quenched and is cooled down with dry ice.
Preferably, when the surfactant is lauryl sodium sulfate, to the cleaning effect of natural biological bone material
More preferably, it is more advantageous to the combination of itself and active inorganic material.
It is preferred that when removing the organic matter of natural biological bone material, removing the ingredients such as blood fat and marrow in S1 step
And sufficiently rinse, 30-180min then, which is impregnated, with hydrogen peroxide ultrasound further removes fat constituent, it is further with surfactant
It is sufficiently being washed and dried after cleaning with water.
It is preferred that after inorganic material calcining, being ground again after water quenching is dry in S2 step.
It is preferred that in the S3 step, after being first sufficiently mixed natural biological bone material and active inorganic material in vessel, carrying
It is mixed by ultrasonic vibration.
It is preferred that after calcining, being quenched with dry ice in S4 step, biologically active inorganic bone branch is obtained after dry
Frame material.It is only quenched with dry ice, does not touch moisture, the activity of active material can be kept.
The present invention second is designed to provide one kind, and by the above method, (preferable embodiment party can be obtained by being combined by optimum condition
Formula) biologically active inorganic bone holder material is prepared.
The present invention has the beneficial effect that:
(1) bone holder material being prepared through the method for the present invention has good biocompatibility, may advantageously facilitate thin
Intracellular growth and creeping substitution, and may advantageously facilitate osteogenic growth and knitting.
(2) the method for the present invention is conducive to the combination of inorganic material and natural biological bone material, can preferably retain inorganic
The property of active material, and bone holder material obtained has good mechanical strength.
(3) can guarantee the safety of finished product through the method for the present invention, the immunological rejection after excluding implantation host with
The risk of transmission.
(4) the inorganic bone holder material being prepared by the method for the invention is in biocompatibility, mechanical strength, self-bone grafting
Preferable effect is presented in the various aspects such as property and safety, is conducive to it in the popularization and application in bone defect healing field.
Specific embodiment
The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention..
Embodiment 1
Ox back bone cancellous bone is taken, the strip structure of 1cm*1cm*2cm is prepared into, is rinsed with water 15min removal residual
Blood marrow components.Then 60min removal fat is sufficiently impregnated with the hydrogen peroxide that concentration is 30%, with 5% dodecyl
Then sodium sulphate washing by soaking 15min is rinsed with water the residuals such as non-foam and 50 degrees Celsius of dryings, is weighed as 1.86g.
By SiO227 parts, Na2CO328 parts, CaCO325 parts, MgCO310 parts and P2O510 parts are sufficiently mixed, 1200 DEG C of calcinings
10h is ground spare after water quenching is dry；
Above-mentioned natural biological bone is sufficiently mixed in Boiling tube with active inorganic material, and is submerged wherein.Ultrasonic vibration
Natural biological bone is taken out after 60min, the load capacity that weighing calculates its inorganic active material is 23.5%.
750 degrees Celsius of calcining 20min, are quenched to obtain biologically active nothing with carbon dioxide after taking-up in Muffle furnace
Machine bone holder material.
Embodiment 2
Ox back bone cancellous bone is taken, the nutty structure of several 0.5cm*0.5cm*0.5cm is prepared into, is rinsed with water
15min removes remaining blood marrow components.Then 60min removal fat is sufficiently impregnated with the hydrogen peroxide that concentration is 30%, used
Then 5% lauryl sodium sulfate washing by soaking 15min is rinsed with water the residuals such as non-foam and 50 degrees Celsius of dryings, claim
Weight is 1.6g.
By SiO220 parts, Na2CO330 parts, CaCO330 parts, MgCO310 parts and P2O510 parts are sufficiently mixed, 1150 DEG C of calcinings
10h is ground spare after water quenching is dry.
Above-mentioned natural biological bone is sufficiently mixed in Boiling tube with active inorganic material, and is submerged wherein.Ultrasonic vibration
Natural biological bone is taken out after 30min, the load capacity that weighing calculates its inorganic active material is 9.8%.
850 degrees Celsius of calcining 30min, are quenched to obtain biologically active nothing with carbon dioxide after taking-up in Muffle furnace
Machine bone holder material.
Embodiment 3
Ox back bone cancellous bone is taken, the strip structure of 1cm*1cm*2cm is prepared into, is rinsed with water 15min removal residual
Blood marrow components.Then 60min removal fat is sufficiently impregnated with the hydrogen peroxide that concentration is 30%, with 5% dodecyl
Then sodium sulphate washing by soaking 15min is rinsed with water the residuals such as non-foam and 50 degrees Celsius of dryings, is weighed as 1.65g.
By SiO230 parts, Na2CO320 parts, CaCO320 parts, MgCO315 parts and P2O515 parts are sufficiently mixed, 1250 DEG C of calcinings
10h is ground spare after water quenching is dry.
Above-mentioned natural biological bone is sufficiently mixed in Boiling tube with active inorganic material, and is submerged wherein.Ultrasonic vibration
Natural biological bone is taken out after 45min, the load capacity that weighing calculates its inorganic active material is 14.5%.
950 degrees Celsius of calcining 45min, are quenched to obtain biologically active nothing with carbon dioxide after taking-up in Muffle furnace
Machine bone holder material.
Embodiment 4
Ox back bone cancellous bone is taken, the strip structure of 1cm*1cm*2cm is prepared into, is rinsed with water 15min removal residual
Blood marrow components.Then 60min removal fat is sufficiently impregnated with the hydrogen peroxide that concentration is 30%, with 5% dodecyl
Then sodium sulphate washing by soaking 15min is rinsed with water the residuals such as non-foam and 50 degrees Celsius of dryings, is weighed as 1.7g.
By SiO220 parts, Na2CO340 parts, CaCO320 parts, MgCO310 parts and P2O510 parts are sufficiently mixed, 1200 DEG C of calcinings
10h is ground spare after water quenching is dry.
Above-mentioned natural biological bone is sufficiently mixed in Boiling tube with active inorganic material, and is submerged wherein.Ultrasonic vibration
Natural biological bone is taken out after 10min, the load capacity that weighing calculates its inorganic active material is 5.5%.
950 degrees Celsius of calcining 60min, are quenched to obtain biologically active nothing with carbon dioxide after taking-up in Muffle furnace
Machine bone holder material.
Embodiment 5
Pig back leg cancellous bone bone is taken, the nutty structure of several 0.5cm*0.5cm*0.5cm is prepared into, is rinsed with water
15min removes remaining blood marrow components.Then 60min removal fat is sufficiently impregnated with the hydrogen peroxide that concentration is 30%, used
Then 5% lauryl sodium sulfate washing by soaking 15min is rinsed with water the residuals such as non-foam and 50 degrees Celsius of dryings, claim
Weight is 1.4g.
By SiO225 parts, Na2CO330 parts, CaCO335 parts, MgCO35 parts and P2O55 parts are sufficiently mixed, 1200 DEG C of calcinings
10h is ground spare after water quenching is dry.
Above-mentioned natural biological bone is sufficiently mixed in Boiling tube with active inorganic material, and is submerged wherein.Ultrasonic vibration
Natural biological bone is taken out after 30min, the load capacity that weighing calculates its inorganic active material is 4.5%.
950 degrees Celsius of calcining 60min, are quenched to obtain biologically active nothing with carbon dioxide after taking-up in Muffle furnace
Machine bone holder material.
Comparative example 1
Ox back bone cancellous bone is taken, the strip structure of 1cm*1cm*2cm is prepared into, is rinsed with water 15min removal residual
Blood marrow components.Then 60min removal fat is sufficiently impregnated with the hydrogen peroxide that concentration is 30%, with 5% dodecyl
Then sodium sulphate washing by soaking 15min is rinsed with water the residuals such as non-foam and 50 degrees Celsius of dryings, is weighed as 2.32g.
By SiO227 parts, Na2CO328 parts, CaCO325 parts, MgCO310 parts and P2O510 parts be sufficiently mixed it is spare；
Above-mentioned natural biological bone is sufficiently mixed in Boiling tube with active inorganic material, and is submerged wherein.Ultrasonic vibration
Natural biological bone is taken out after 60min, the load capacity that weighing calculates its inorganic active material is 14.85%.
750 degrees Celsius of calcining 20min, are quenched to obtain inorganic bone holder material with carbon dioxide after taking-up in Muffle furnace.
Biological bone does not adhere to sufficiently with other inorganic active materials, hence it is evident that separation, it is powdered at half.
Comparative example 2
Ox back bone cancellous bone is taken, the strip structure of 1cm*1cm*2cm is prepared into, is rinsed with water 15min removal residual
Blood marrow components.Then 60min removal fat is sufficiently impregnated with the hydrogen peroxide that concentration is 30%, with 5% dodecyl
Then sodium sulphate washing by soaking 15min is rinsed with water the residuals such as non-foam and 50 degrees Celsius of dryings, is weighed as 1.65g.
By SiO227 parts, Na2CO328 parts, CaCO325 parts, MgCO310 parts and P2O510 parts be sufficiently mixed it is spare；
Above-mentioned natural biological bone is sufficiently mixed in Boiling tube with active inorganic material, and is submerged wherein.Ultrasonic vibration
Natural biological bone is taken out after 60min, the load capacity that weighing calculates its inorganic active material is 17.65%.
1250 degrees Celsius of calcining 20min, are quenched to obtain inorganic bone holder material with carbon dioxide after taking-up in Muffle furnace.
This bracket poor mechanical property, at powdered.
Comparative example 3
Ox back bone cancellous bone is taken, the strip structure of 1cm*1cm*2cm is prepared into, is rinsed with water 15min removal residual
Blood marrow components.Then 60min removal fat is sufficiently impregnated with the hydrogen peroxide that concentration is 30%, with 5% dodecyl
Then sodium sulphate washing by soaking 15min is rinsed with water the residuals such as non-foam and 50 degrees Celsius of dryings, is weighed as 1.86g.
By SiO227 parts, Na2CO328 parts, CaCO325 parts, MgCO310 parts and P2O510 parts are sufficiently mixed, 1200 DEG C of calcinings
10h is ground spare after water quenching is dry；
Above-mentioned natural biological bone is sufficiently mixed in Boiling tube with active inorganic material, and is submerged wherein.Ultrasonic vibration
Natural biological bone is taken out after 60min, the load capacity that weighing calculates its inorganic active material is 23.5%.
1200 degrees Celsius of calcining 2h, are quenched to obtain inorganic bone holder material with carbon dioxide after taking-up in Muffle furnace.This
Bracket poor mechanical property, at powdered.
Comparative example 4
Ox back bone cancellous bone is taken, the strip structure of 1cm*1cm*2cm is prepared into, is rinsed with water 15min removal residual
Blood marrow components.Then 60min removal fat is sufficiently impregnated with the hydrogen peroxide that concentration is 30%, with 5% dodecyl
Then sodium sulphate washing by soaking 15min is rinsed with water the residuals such as non-foam and 50 degrees Celsius of dryings, is weighed as 1.62g.
By SiO227 parts, Na2CO328 parts, CaCO325 parts, MgCO310 parts and P2O510 parts are sufficiently mixed, 1200 DEG C of calcinings
10h is ground spare after water quenching is dry；
Above-mentioned natural biological bone is sufficiently mixed in Boiling tube with active inorganic material, and is submerged wherein.Ultrasonic vibration
Natural biological bone is taken out after 60min, the load capacity that weighing calculates its inorganic active material is 26.5%.
400 degrees Celsius of calcining 2h, are quenched to obtain inorganic bone holder material with carbon dioxide after taking-up in Muffle furnace.This branch
Frame inorganic active material and natural biological bone are unbonded, separated state.
1 Mechanics Performance Testing of experimental example
By Examples 1 to 2, the resulting bone holder material of comparative example 1~4 indulges that stand on the load of material universal testing machine flat respectively
Platform keeps bone block long axis vertical with platform, bone block top and bottom and platform parallel.Vertical compression force, cross beam movement are applied to bone block
Speed is 1mm/s, according to its compressive ultimate strength of maximal destruction load measurement, the results are shown in Table 1.
Table 1
| Embodiment 1 | Embodiment 2 | Comparative example 1 | Comparative example 2 | Comparative example 3 | Comparative example 4 |
| 4.85MPa | 5.52MPa | 0.13MPa | —— | —— | 3.22 |
| 3.66MPa | 4.58MPa | 0.08MPa | —— | —— | 3.58 |
It can be obtained by data in table, technical solution of the present invention maintains biologically active inorganic bone bracket material well
The mechanical strength of material, mechanical property have even surmounted that treatment temperature is relatively low, comparison without composite inorganic active material
The mechanical strength of example 4.
The test of 2 pH value of experimental example
Examples 1 to 2 is detected, the pH value of the resulting bone holder material of comparative example 1~4 the results are shown in Table 2.
Table 2
This method preferably remains the property of inorganic active material.The not formed active material of various mixtures in comparative example 1
Expect ingredient, the reaction of the various inorganic compositions ingredients in comparative example 2 not as expected forms active constituent, in comparative example 3
Melting recrystallization of the inorganic active ingredient due to again passing by high-temperature burning process, forms crystalline constituents, changes inorganic
The original performance of active constituent, since calcination temperature is lower in comparative example 4, inorganic active material and biological bone component from state,
The two keeps performance independent substantially, thus shows the alkalescent of inorganic active material.
Experimental example 3
Example 1~2, the resulting bone holder material of comparative example 1~4 are dipped in DMEM according to the ratio of 0.1kg/L respectively
In culture solution, 37 DEG C of constant temperature holdings prepare leaching liquor for 24 hours, and 10*10 is made in mesenchymal stem cell and the leaching liquor6L-
1 cell suspension is inoculated in 96 well culture plates, the CO that volume fraction is 0.05 under the conditions of 37 DEG C2Culture in incubator.Exist respectively
The 1 piece of culture plate of taking-up in 1st, 3,5,7 day in wavelength is at 500nm with microplate reader after 10 microlitres of CCK-8 reagent culture 4h are added
Absorbance is measured, cell is calculated with respect to appreciation rate, the results are shown in Table 3.Cell is inhaled with respect to appreciation rate=experimental group absorbance/control group
Luminosity.
Table 3
| Time (d) | Embodiment 1 | Embodiment 2 | Comparative example 1 | Comparative example 2 | Comparative example 3 |
| 1 | 95% | 92% | 88% | 85% | 80% |
| 3 | 101% | 98% | 90% | 80% | 75% |
| 5 | 118% | 101% | 90% | 80% | 75% |
| 7 | 106% | 101% | 80% | 75% | 83% |
As seen from the above table, the cytotoxicity very little of the material of embodiment 1 and embodiment 2 is zero level in incubation with
On, the cytotoxicity of comparative example 1-3 is 1-2 grades, mainly due to the two inorganic active material and the calcined product of nature bone
Biocompatibility is more preferable, can promote the Proliferation, Differentiation of cell to a certain extent, and this performance can be more in clinical use
It shows as well promoting Bone Defect Repari or tissue repair, effectively shortens the healing times of damaged tissues.
Experimental example 4
It is to be diluted to 10* in the DMEM culture medium of 0.1 fetal calf serum containing volume fraction that mesenchymal stem cell, which is added,
106L-1 density.By Examples 1 to 2, the resulting bone holder material of comparative example 1~4 is respectively with being put into the training of 48 holes after abundant infiltration
It supports in plate, cell suspension drips on the surface of the material, and culture medium is added after 1h, continuously cultivates 5d, observes material side under inverted microscope
Marginal cell adherent growth situation, control group use the culture of culture medium blank, the results are shown in Table 4.
Table 4
Mesenchymal stem cell is grown around edge of materials, and as time went on, the cell quantity observed gradually increases
Add.Do not occur cytomorphosis or necrosis in the experimentation of Examples 1 to 2, the cellular morphology of material group and blank control group without
Notable difference, quantity rough estimate is higher and blank control group.And in comparative example 1~4, the adhesiving effect of cell and material compared with
Difference, and there is certain fragmentation effect to cell, it is seen that Biocompatibility is significantly lower than embodiment group.
Although above having used general explanation, specific embodiment and test, the present invention is made to retouch in detail
It states, but on the basis of the present invention, it can be made some modifications or improvements, this is apparent to those skilled in the art
's.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to claimed
Range.
Claims (10)
1. a kind of preparation method of biologically active inorganic bone holder material, which comprises the following steps:
(1) inorganic material is calcined at 1100-1300 DEG C, obtains active inorganic material；
(2) the active inorganic material is mixed with natural biological bone material, obtains the natural biological with active inorganic material
Bone material；
(3) the natural biological bone material with active inorganic material is calcined at 400-1000 DEG C.
2. the method according to claim 1, wherein the inorganic material is calcined at 1150-1250 DEG C.
3. method according to claim 1 or 2, which is characterized in that by the natural biological with active inorganic material
Bone material is calcined at 750-950 DEG C.
4. method described in any one of claim 1 to 3, which is characterized in that when the calcining of the active inorganic material
Between be 8~12h；Preferably 10h；
And/or the calcination time of the natural biological bone material with active inorganic material is 10-120min；Preferably 20-
60min。
5. method according to any one of claims 1 to 4, which is characterized in that the inorganic material includes following weight
Part component: SiO215-50 parts, Na2CO315-50 parts, CaCO310-40 parts, MgCO35-35 parts, P2O55-20 parts；
Preferably SiO220-40 parts, Na2CO320-40 parts, CaCO315-30 parts, MgCO35-15 parts, P2O510-15 parts.
6. method according to any one of claims 1 to 5, which is characterized in that the active inorganic material and the day
So the weight ratio of biology bone material is 1:1-30.
7. method described according to claim 1~any one of 6, which is characterized in that the active inorganic material and the day
So biology bone material is mixed by ultrasonic vibration；It is preferred that incorporation time is 15-60min.
8. method according to any one of claims 1 to 7, which is characterized in that the partial size of the active inorganic material is
Within 45 microns.
9. method described according to claim 1~any one of 8, which comprises the following steps:
S1, natural biological bone material is taken, after removing organic matter, is impregnated and be cleaned by ultrasonic with surfactant solution, then purified water
It rinses well；
S2, the inorganic material after calcining pretreatment, is obtained active inorganic material and is ground to its grain at 1100-1300 DEG C
Diameter is within 45 microns；
S3, by the natural biological bone material Jing Guo S1 step and the active inorganic material ultrasonic vibration mixing 15- Jing Guo S2 step
60min obtains the natural biological bone material with active inorganic material；
S4, the resulting natural biological bone material with active inorganic material of S3 step is calcined at 400-1000 DEG C, is used in combination
Dry ice quenching cooling.
10. a kind of biologically active inorganic bone holder material, which is characterized in that as described in any one of claim 1~9
Method is prepared.
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