CN108578773A - Short route prepares the method for porous block xenogenesis bone renovating material and bone renovating material obtained by this method - Google Patents
Short route prepares the method for porous block xenogenesis bone renovating material and bone renovating material obtained by this method Download PDFInfo
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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
- A61L27/3604—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 human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
- A61L27/3608—Bone, e.g. demineralised bone matrix [DBM], bone powder
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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
- 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
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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
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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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
- 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
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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
- A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
Abstract
The present invention provides a kind of preparation method of porous block xenogenesis bone renovating material：1) cancellous bone of mammal is cut into bulk, after washing with water drying, uses hydrogenperoxide steam generator and sodium hydroxide solution to impregnate preliminary organics removal respectively, be eluted with water, it is dry；2) it will be placed in pressure-bearing closed container together with the cancellous bone of preliminary organics removal and alkaline solution, heat and keep the temperature, wash with water, it is dry；3) it will be placed in pressure-bearing closed container together with cancellous bone and distilled water, heat and keep the temperature, wash with water, it is dry；4) calcining and sterilization treatment.The present invention also provides porous block xenogenesis bone renovating materials made from above-mentioned preparation method.The preparation method of the present invention can thoroughly removing causes the fat and protein that immunizing antigen reacts under lower temperature conditions, there is no poisonous and hazardous organic solvent pollution in processing procedure, xenogenesis bone material that treated is in weak crystalline texture, and contain a large amount of carbonate, it can preferably promote bone tissue regeneration.
Description
Technical field
The invention belongs to bio-medical engineering material fields, and in particular to it is a kind of prepare in surgical operation to bone tissue
The method for the porous block xenogenesis bone renovating material repaired and bone renovating material obtained by this method.
Background technology
The bone tissue defect caused by the factors such as wound, tumour, infection is Orthopedic Clinical common disease.Bone grafting is
Common restorative procedure, bone collection are broadly divided into autologous bone transplanting, homogeneous allogenic bone transplantation and bone xenograft.First two method
Primary limitation is that supply source lack, easily occur district complication, there are disease infect potential, bone xenograft is bone defect
Reparation provides new idea and method.
It is very high to the requirement of xenogenesis bone renovating material in bone collection operation, need xenogenesis bone renovating material to have following spy
Point：(1) fat and protein triggered an immune response is free of；(2) it can be prepared into certain size, convenient for filling；(3) have
Osteoinductive and osteoconductive；(4) biological degradability of good biocompatibility and appropriateness, degradation speed need and bone tissue
Reproduction speed matches, and the catabolite in human body is harmless；(5) have and support bone cell growth and function differentiation
Surface chemical property and micro-structure；(6) easy to process, disinfection, storage.
The preparation key of xenogenesis bone renovating material is that removing fat, protein etc. easily cause antigenic organic matter.Currently,
The method that the degreasing of xenogenesis bone renovating material, de- albumen mainly use chemical immersion processing, high-temperature calcination.Chemical immersion processing is logical
It is often used the toxic solvents such as ethylenediamine, acetone, chloroform, methanol, ether.Largely larger environment pressure can be caused using toxic solvent
Power.Further, since xenogenesis bone renovating material is in porous structure, toxic solvent is difficult clean by cleaning treatment, can be caused toxic
Chemical agent residue destroys the bioactivity of bone- xenograft.Sodium hydroxide and hydrogen peroxide Combined Treatment in chemical immersion processing method
Method is also often used, but it can only partially remove the antigenicity of bone- xenograft, and with the extension of soaking time, intensity and chemistry
Composition can have greatly changed.High-temperature calcination refer under the high temperature conditions (600 DEG C of ＞) to bone- xenograft carry out calcining removal have
Machine object, high-temperature calcination can destroy the weak crystalline texture of xenogenesis bone renovating material, and the carbonate in bone can also decompose, and make bone- xenograft
Repair materials lose bioactivity.So toxic solvent infusion method used at present and high-temperature calcination cannot all meet xenogenesis
The preparation requirement of bone.
Murugan R et al. (Murugan R, Ramakrishna S, Rao K P.Nanoporous hydroxy-
Carbonate apatite scaffold made of natural bone [J] .Materials Letters, 2006,60
(23)：2844-2847.) first use acetone and the preliminary organics removal of washed with ether ox cortex bone, then by 4%NaOH solution and
Ox cortex bone carries out alkali heat-treatment together, and xenogenesis bone renovating material is obtained finally by the calcining at 500 DEG C.It is prepared by this method
Two kinds of toxic solvents of acetone and ether have been used in the process, can cause the residual of toxic solvent.In addition, NaOH processing and higher temperatures
The calcination temperature of degree significantly destroys the weak crystalline texture, bioactivity and its distinctive microstructure of bone- xenograft.
Barakat N A M et al. (Barakat N A M, Khil M S, Omran A M, et al.Extraction
of pure natural hydroxyapatite from the bovine bones bio waste by three
Different methods [J] .Journal of materials processing technology, 2009,209 (7)：
3408-3415.) using ox bone as raw material, fat is removed using acetone soln, and be prepared into 450 μm of powder below.Again
It is prepared for nanometer hydroxyapatite powder by the hot 5h of NaOH solution alkali using 25% concentration at a temperature of 250 DEG C.The method is made
Xenogenesis bone material be highly crystallized nano-grade hydroxy apatite powder, completely lost the more of ox bone (especially cancellous bone)
Tie up the crystal structure characteristic of pore space structure and weak crystallization.In addition, having used acetone soln in preparation process, can make obtained different
There are toxic dissolving residuals in kind bone renovating material.
The production of Geistlich companies(Geistlich, Switzerland) is a kind of in bone collection operation
In widely used heterotransplantatioof of bones.The said firm U.S.PatentNo 5,167,961 patent (Lussi, Heinz；
Geistlich, Peter.Process for preparing high purity bone mineral.U.S.Patent
No5,167,961,1992.) the preliminary organics removal of toxic solvent ethylenediamine is first used in, then by its special solution and is gone
Ionized water cleans repeatedly, finally carries out 250 DEG C~600 DEG C calcinings again and is prepared for xenogenesis bone material.This method is likely to occur toxic
Dissolvent residual, and this method preparation time is more than 15 days, and preparation flow is long.Zimmermann et al. (Zimmermann C
E, Gierloff M, Hedderich J, et al.Biocompatibility of bone graft substitutes：
effects on survival and proliferation of porcine multilineage stem cells in
Vitro [J] .Folia morphologica, 2011,70 (3)：154-160.) the study found that willLeachate and thin
Born of the same parents' co-incubation, only 1/3 adherent cell survive, side illustrationResidual fraction toxic chemical solvent.
Therefore, being badly in need of the problem of the bone- xenograft preparation solved at present is：(1) toxic solvent is not used in preparation process, is prevented
Only destroy the bioactivity of bone- xenograft；(2) certain size can be prepared and there is the different of the original micro-nano pore space structure of bone- xenograft
Kind bone bone block, convenient for the bone defect healing under specified conditions；(3) temperature of preparation process is relatively low, reduces to the weak crystallization of bone- xenograft
The influence of property and carbonate content.
Invention content
The object of the present invention is to provide a kind of new bone- xenograft preparation methods, can be prepared with abundant more by the method
Pore structure and in weak crystalline state xenogenesis bone renovating material.
Another object of the present invention is to provide porous block xenogenesis bone renovating material made from above-mentioned preparation method.
Technical solution：The present invention provides a kind of preparation method of porous block xenogenesis bone renovating material, includes the following steps：
1) the blocky cancellous bone after preliminary organics removal is immersed in alkaline solution, is placed in pressure-bearing closed container,
1~12 hour is kept the temperature at 100~240 DEG C after being heated to 100~240 DEG C, cancellous bone is taken out after cooling and is washed with water, it is dry；
2) by step 1), treated that cancellous bone is immersed in distilled water or deionized water, is placed in pressure-bearing closed container,
1~12 hour is kept the temperature at 100~240 DEG C after being heated to 100~240 DEG C, cancellous bone is taken out after cooling and is washed with water, it is dry；
3) by step 2), treated carries out sterilization treatment after cancellous bone calcines 4~24 hours at 300~480 DEG C, obtains
The porous block xenogenesis bone renovating material.
The method of above-mentioned preliminary organics removal includes：
A) cancellous bone for being cut into block-like mammal is washed with water until without visible myeloid tissue, after dry, is used
Cleaning, drying after hydrogenperoxide steam generator impregnates；
B) by step a), treated that cancellous bone is impregnated with sodium hydroxide solution, then washes with water, dry.
The method of above-mentioned preliminary organics removal is impregnated by washing, hydrogenperoxide steam generator and sodium hydroxide solution impregnates,
The fat and protein in cancellous bone can tentatively be removed.
Step 1), can substantially cleared fat, protein except in cancellous bone by alkali heat-treatment；Step 2) by hydro-thermal at
Reason can remove the alkali adhered in cancellous bone after step 1) processing；Step 3) can be eliminated by low temperature calcination and sterilization treatment
The germ that itself is carried in mammal cancellous bone.
The blocky cancellous bone of the present invention may be derived from common mammal, such as pig, sheep, horse.
In the method for above-mentioned preliminary organics removal, in step a), the cancellous bone of mammal is cut into 0.1cm3~
50cm3Bulk, wash with water and preferably rinse bone block with giant, until bone tissue color and luster white is partially yellow, without visible marrow
It is then 12 hours dry in drying box until tissue；The mass fraction of hydrogen peroxide is preferably 10% in hydrogenperoxide steam generator
~70%, the condition impregnated with hydrogenperoxide steam generator is to be impregnated 12~48 hours at 5~70 DEG C；It is soaked in hydrogenperoxide steam generator
Cancellous bone after bubble is cleaned repeatedly with distilled water, then 12 hours dry in drying box.
In step b), the cancellous bone after drying is impregnated 12~48 hours in sodium hydroxide solution at 5~70 DEG C, concentration
Preferably 0.5~4M；Cancellous bone after being impregnated in sodium hydroxide solution is cleaned repeatedly with distilled water, dry 12 in drying box
Hour；
In step 1), the pH value of alkaline solution is preferably 8~13, and alkaline solution is sodium hydroxide, potassium hydroxide, hydroxide
The solution or a variety ofization of a kind of compound in calcium, sodium carbonate, sodium bicarbonate, potassium carbonate, saleratus, potassium silicate and sodium metasilicate
Close the mixed solution of object；The volume ratio of cancellous bone and alkaline solution is 1: 20~1: 80；Pressure-bearing closed container can be reaction kettle,
Reaction kettle is kept the temperature 1~12 hour in heater box, holding temperature is 100~240 DEG C, after reaction kettle drops to room temperature, takes out pine
Matter bone is cleaned with distilled water, is dry repeatedly, is repeated 1~4 time.
In step 2), by after drying cancellous bone and distilled water be placed in together in closed container, cancellous bone and distilled water
Volume ratio is 1: 20~1: 80, and reaction kettle keeps the temperature 1~12 hour in heater box, and holding temperature is 100~240 DEG C, reaction kettle
Room temperature is dropped to, cancellous bone is taken out and is cleaned repeatedly with distilled water, is dry, repeat 1~4 time.
In step 1) and step 2), it is preferable that the temperature for heating and keeping the temperature in pressure-bearing closed container is 180~240 DEG C.
Preferably, above-mentioned calcination temperature is 300~400 DEG C, and above-mentioned irradiation sterilization is co-60 radiation sterilizing or ethylene oxide
Sterilizing etc..Another aspect of the present invention provides a kind of porous block xenogenesis bone renovating material, the porous block xenogenesis bone renovating material
It is made by above-mentioned preparation method.
Advantageous effect：Porous block xenogenesis bone renovating material prepared by the method for the present invention has the chemistry consistent with people's bone
Ingredient, material pore space structure and weak crystalline texture simulate the structure and ingredient of body bone tissue, maintain different to the maximum extent
The bioactivity of kind bone renovating material, can promote the growth reparation of bone tissue.The preparation method of the present invention is simple, significantly contracts
Subtract preparation time, be the preparation method of short route, and raw material sources are extensive, is suitble to large-scale industrialization production, Neng Gouxian
Writing reduces production cost, and cheap eutherapeutic bone renovating material is provided for patient.
Description of the drawings
Fig. 1 is the photomacrograph of the blocky xenogenesis bone renovating material prepared using the method for the present invention；
Fig. 2 is the scanning electron microscope diagram piece of the porous block xenogenesis bone renovating material prepared using the method for the present invention
(100 times of amplification)；
Fig. 3 is the X-ray diffraction picture of porous block xenogenesis bone renovating material made from different preparation methods；
Fig. 4 is the Fourier transform infrared spectroscopy picture of the porous block xenogenesis bone material prepared using the method for the present invention.
Specific implementation mode
Embodiment 1
The preparation method of porous block xenogenesis bone material is as follows：
(1) cancellous bone is extracted：
(a) fresh ox vertebra is collected, pollutant, freezen protective are avoided contact with.
(b) the ox vertebra of freezing is thawed and is cleaned up, the cancellous bone of ox is cut by bone sawing machine, cancellous bone is cut into
2cm3Bulk is rinsed repeatedly with giant, until bone tissue color and luster white is partially yellow, without visible myeloid tissue until, in drying
It is 12 hours dry in case.
(2) pretreatment of cancellous bone：
(a) hydrogen peroxide solution is handled
It is 10% hydrogen peroxide by the cancellous bone mass fraction after step (1) processing is dry, is impregnated under 25 DEG C of environment
12 hours, the cancellous bone after immersion was cleaned repeatedly with distilled water, 12 hours dry in drying box.
(b) sodium hydroxide solution is handled
It by the sodium hydroxide of cancellous bone a concentration of 1M of the step (a) after dry, impregnates 12 hours, soaks under 25 DEG C of environment
Cancellous bone after bubble is cleaned repeatedly with distilled water, 12 hours dry in drying box.
(3) alkali heat-treatment of cancellous bone：
Step (2) treated cancellous bone is mixed with sodium hydroxide solution and is placed in closed reactor, hydroxide
Sodium solution pH value is 13, and the volume ratio of cancellous bone and sodium hydroxide solution is 1: 20, and reaction kettle keeps the temperature 2 hours in heater box,
Holding temperature is 180 DEG C, and reaction kettle drops to room temperature, takes out cancellous bone and is cleaned repeatedly with distilled water, is dry, is repeated 3 times.
(4) hydro-thermal process of cancellous bone：
Step (3) treated cancellous bone and distilled water are mixed and are placed in closed reactor, cancellous bone and distillation
The volume ratio of water is 1: 20, and reaction kettle keeps the temperature 2 hours in heater box, and holding temperature is 180 DEG C, and reaction kettle drops to room temperature, takes
It is to clean repeatedly, is dry to go out cancellous bone distillation, is repeated 2 times.
(5) calcination processing of cancellous bone：
By step (4), treated that cancellous bone is put into high temperature furnace calcines, and heating rate is 10 DEG C/min, is warming up to 400
DEG C heat preservation 12 hours, Temperature fall take out cancellous bone it is spare.
(6) sterilization treatment of cancellous bone：
Cancellous bone is sterilized (irradiation dose 30KGy) with co-60 radiation, obtains xenogenesis bone renovating material.
Structure and ingredient characterization are carried out to xenogenesis bone renovating material, characterization result is as shown in table 1 and Fig. 1~4.
Table 1 is the porous block xenogenesis bone material prepared using the method for the present invention and commercially available same type bone renovating material Switzerland
Geistlich'sElemental analysis, it can be seen that the bone- xenograft of preparation is free of organic matter, and containing more
CO3 2-, Zakaria F A et al. (Zakaria F A, Marsad N H, ManafA Y A, et a1.Characterisation
of carbonated apatite for possible application in biomedical implants[J]
.Materials Research Innovations, 2009,13 (3)：309-312.) find that carbonate helps to improve biology
Activity, so xenogenesis bone renovating material prepared by this method is more advantageous to the reparation of bone tissue.
Table 1
Fig. 1 is the photomacrograph of the blocky xenogenesis bone renovating material prepared using the method for the present invention, obtained as seen from Figure 1
Xenogenesis bone material is in the distinctive milky of hydroxyapatite, illustrates that surface has no remaining organic matter.
Fig. 2 is the scanning electron microscope diagram piece of the porous block xenogenesis bone renovating material prepared using the method for the present invention
(100 times of amplification), as can be seen from Figure 2 xenogenesis bone material obtained is in three-dimensional pore space structure, and big pore size is more than 100um,
It is also distributed several small structures therebetween, such pore space structure is conducive to the reparation of bone tissue.
The X-ray diffraction picture of porous block xenogenesis bone renovating material made from methods and calcination method of the Fig. 3 for the present invention,
As seen from Figure 3, xenogenesis bone renovating material made from method of the invention and calcination method is all hydroxyapatite ingredient, but this
Bone renovating material peak shape made from inventive method is wider, is in weak crystalline state, by calculating, crystallinity 42%, far smaller than
Xenogenesis bone renovating material prepared by calcination method.Wherein, above-mentioned calcination method specifically refers to：
(1) extraction of cancellous bone
Fresh ox vertebra is collected, pollutant, freezen protective are avoided contact with.The ox vertebra of freezing is thawed, it is special with oral cavity
Muscle and connective tissue attached thereto are rejected with scraping.
Cancellous bone is cut into 2cm by the cancellous bone that ox is cut by bone sawing machine3Bulk, rinsed repeatedly with giant, directly
It is partially yellow to bone tissue color and luster white, without visible myeloid tissue until, dry 12 hours in drying box.
(2) it pre-processes
By the bovine cancellous bone after drying under room temperature environment, it is put into the H that mass fraction is 30%2O2It is small that 12 are impregnated in solution
When, the bovine cancellous bone after immersion is cleaned repeatedly with distilled water, 12 hours dry in drying box.
By the bovine cancellous bone after above-mentioned drying under room temperature environment, it is put into the NaOH solution of a concentration of 1mol/L and impregnates 12
Hour, the bovine cancellous bone after immersion is cleaned repeatedly with distilled water, 12 hours dry in drying box.
(3) calcination processing
Bovine cancellous bone after drying is put into crucible, crucible is placed in tube furnace and is calcined at 900 DEG C, calcination atmosphere is
Air, heating rate are 5 DEG C/min, and soaking time is 3 hours, then takes out sample after furnace cooling.
Fig. 4 is the Fourier transform infrared spectroscopy picture of the porous block xenogenesis bone material prepared using the method for the present invention,
In Fig. 4 it can be found that in 1043cm-1、606cm-1And 569cm-1There is typical PO in place4 3-Peak, show that xenogenesis aggregate is made
Material is apatite structure, in 1418cm-1Place shows to deposit in xenogenesis bone renovating material crystal structure obtained there are two division peaks
In CO3 2-.Hence, it can be determined that the xenogenesis bone material prepared is typical carbonated hydroxyapatite.
Embodiment 2
The preparation method of porous block xenogenesis bone material is as follows：
(1) cancellous bone is extracted：
The cancellous bone of pig is cut into 8cm3Bulk is rinsed repeatedly with giant, until bone tissue color and luster white is partially yellow, nothing
It can be seen that until myeloid tissue, it is 12 hours dry in drying box.
(2) pretreatment of cancellous bone：
(a) hydrogen peroxide solution is handled
The hydrogen peroxide for being 70% by the cancellous bone mass fraction after step (1) processing is dry, impregnates under 5 DEG C of environment
48 hours, the cancellous bone after immersion was cleaned repeatedly with deionized water, 12 hours dry in drying box.
(b) sodium hydroxide solution is handled
By cancellous bone a concentration of 0.5M potassium hydroxide of the step (a) after dry, impregnates 12 hours, soak under 70 DEG C of environment
Cancellous bone after bubble is cleaned repeatedly with distilled water, 12 hours dry in drying box.
(3) alkali heat-treatment of cancellous bone：
Step (2) treated cancellous bone is mixed with potassium bicarbonate solution and is placed in closed reactor, hydroxide
Sodium solution pH value is 8, and the volume ratio of cancellous bone and potassium bicarbonate solution is 1: 80, and reaction kettle keeps the temperature 12 hours in heater box,
Holding temperature is 240 DEG C, and reaction kettle drops to room temperature, takes out cancellous bone and is cleaned repeatedly with distilled water, is dry, cleaning, dry mistake
Journey is repeated 3 times.
(4) hydro-thermal process of cancellous bone：
Step (3) treated cancellous bone and distilled water are mixed and are placed in closed reactor, cancellous bone and distillation
The volume ratio of water is 1: 80, and reaction kettle keeps the temperature 12 hours in heater box, and holding temperature is 240 DEG C, and reaction kettle drops to room temperature, takes
It is to clean repeatedly, is dry to go out cancellous bone distillation, is repeated 4 times.
(5) calcination processing of cancellous bone：
By step (4), treated that cancellous bone is put into high temperature furnace calcines, and heating rate is 1 DEG C/min, is warming up to 300 DEG C
Heat preservation 24 hours, it is spare that Temperature fall takes out cancellous bone.
(6) sterilization treatment of cancellous bone：
By cancellous bone ethylene oxide sterilizing, xenogenesis bone renovating material is obtained.
Embodiment 3
The preparation method of porous block xenogenesis bone material is as follows：
(1) cancellous bone is extracted：
The cancellous bone of sheep is cut into 0.1cm3Bulk is rinsed repeatedly with giant, until bone tissue color and luster white is partially yellow,
It is 12 hours dry in drying box until without visible myeloid tissue.
(2) pretreatment of cancellous bone：
(a) hydrogen peroxide solution is handled
It is 30% hydrogen peroxide by the cancellous bone mass fraction after step (1) processing is dry, is impregnated under 70 DEG C of environment
12 hours, the cancellous bone after immersion was cleaned repeatedly with deionized water, 12 hours dry in drying box.
(b) sodium hydroxide solution is handled
By cancellous bone a concentration of 4M sodium hydroxide of the step (a) after dry, impregnates 48 hours, impregnate under 5 DEG C of environment
Cancellous bone afterwards is cleaned repeatedly with distilled water, 12 hours dry in drying box.
(3) alkali heat-treatment of cancellous bone：
Step (2) treated cancellous bone is mixed with sodium carbonate liquor and is placed in closed reactor, sodium hydroxide
Solution pH value is 10, and the volume ratio of cancellous bone and sodium hydroxide solution is 1: 50, and reaction kettle keeps the temperature 1 hour in heater box, is protected
Temperature is 240 DEG C, and reaction kettle drops to room temperature, takes out cancellous bone and is cleaned repeatedly with distilled water, is dry, is repeated 1 times.
(4) hydro-thermal process of cancellous bone：
Step (3) treated cancellous bone and deionized water are mixed and are placed in closed reactor, cancellous bone with steam
The volume ratio of distilled water is 1: 60, and reaction kettle keeps the temperature 1 hour in heater box, and holding temperature is 240 DEG C, and reaction kettle drops to room temperature,
It is to clean repeatedly, is dry to take out cancellous bone distillation, is repeated 1 times.
(5) calcination processing of cancellous bone：
By step (4), treated that cancellous bone is put into high temperature furnace calcines, and heating rate is 0.1 DEG C/min, is warming up to 400
DEG C heat preservation 4 hours, Temperature fall take out cancellous bone it is spare.
(6) sterilization treatment of cancellous bone：
Cancellous bone is sterilized (irradiation dose 30KGy) with co-60 radiation, obtains xenogenesis bone renovating material.
This method solve porous block xenogenesis bone materials thoroughly to remove fat and protein under lower temperature conditions
Problem.Blocky xenogenesis bone material is pre-processed using improved chemical method first, then further passes through the hot method of alkali
Removing fat and protein obtain the porous block bone- xenograft of weak crystallization finally by calcining and irradiation or ethylene oxide sterilizing
Repair materials.Porous block xenogenesis bone renovating material porosity prepared by the present invention, hole traffic, pore size etc. and people
Body cancellous bone is identical, and weak crystalline texture is presented, and is grown into conducive to the tactophily and blood vessel of cell, nerve, promotes bone tissue
It repairs.Raw material sources of the present invention are extensive and cheap, and preparation method is simple, and process does not use toxic chemical, are suitble to extensive
Industrialization production reduces the financial burden for patient.
Claims (8)
1. a kind of preparation method of porous block xenogenesis bone renovating material, which is characterized in that the preparation method includes the following steps：
1) the blocky cancellous bone after preliminary organics removal is immersed in alkaline solution, is placed in pressure-bearing closed container, heated
1~12 hour is kept the temperature at 100~240 DEG C after to 100~240 DEG C, cancellous bone is taken out after cooling and is washed with water, it is dry；
2) by step 1), treated that cancellous bone is immersed in distilled water or deionized water, is placed in pressure-bearing closed container, heats
1~12 hour is kept the temperature at 100~240 DEG C after to 100~240 DEG C, cancellous bone is taken out after cooling and is washed with water, it is dry；
3) by step 2), treated carries out sterilization treatment after cancellous bone calcines 4~24 hours at 300~480 DEG C, obtains described
Porous block xenogenesis bone renovating material.
2. the preparation method of porous block xenogenesis bone renovating material according to claim 1, which is characterized in that step 1)
In, the volume of the bulk cancellous bone is 0.1cm3~50cm3；The method of the preliminary organics removal includes：By blocky spongiosa
Bone wash with water it is partially yellow to bone tissue color and luster white, without visible myeloid tissue until, then use hydrogenperoxide steam generator and strong successively
Aqueous slkali soaking, cleaning, drying.
3. the preparation method of porous block xenogenesis bone renovating material according to claim 1, which is characterized in that step 1)
In, the pressure-bearing closed container is reaction kettle, and the pH value of the alkaline solution is 8~13, the cancellous bone and alkaline solution
Volume ratio is 1: 20~1: 80；Described to wash with water, dry number of repetition is 1~4 time.
4. the preparation method of porous block xenogenesis bone renovating material according to claim 1 or 3, which is characterized in that step
1) in, the alkaline solution is sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, bicarbonate
A kind of solution of compound in potassium, potassium silicate and sodium metasilicate or the mixed solution of multiple compounds.
5. the preparation method of porous block xenogenesis bone renovating material according to claim 1, which is characterized in that step 2)
In, the cancellous bone is 1: 20~1: 80 with the volume ratio of distilled water or deionized water；Described to wash with water, the dry repetition time
Number is 1~4 time.
6. the preparation method of porous block xenogenesis bone renovating material according to claim 1, which is characterized in that step 1) and
In step 2), the temperature of heating and the heat preservation described in the pressure-bearing closed container is 180~240 DEG C.
7. the preparation method of porous block xenogenesis bone renovating material according to claim 1, which is characterized in that step 3)
In, the calcination temperature is 300~400 DEG C, and the method for the sterilization treatment is radiation sterilization or ethylene oxide sterilizing.
8. a kind of porous block xenogenesis bone renovating material, which is characterized in that the porous block xenogenesis bone renovating material is wanted by right
The preparation method described in any one of 1~7 is asked to be made.
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| CN114209883A (en) * | 2021-12-22 | 2022-03-22 | 天新福（北京）医疗器材股份有限公司 | Preparation method of heterogeneous bone repair material |
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