CN105411725B - A kind of bone renovating material preparation method with more-dimensional channels structure - Google Patents
A kind of bone renovating material preparation method with more-dimensional channels structure Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/28—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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
- A61L27/425—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of phosphorus containing material, 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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
- A61L27/427—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of other specific inorganic materials not covered by A61L27/422 or A61L27/425
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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
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30108—Shapes
- A61F2002/30199—Three-dimensional shapes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30316—The prosthesis having different structural features at different locations within the same prosthesis; Connections between prosthetic parts; Special structural features of bone or joint prostheses not otherwise provided for
- A61F2002/30329—Connections or couplings between prosthetic parts, e.g. between modular parts; Connecting elements
- A61F2002/30383—Connections or couplings between prosthetic parts, e.g. between modular parts; Connecting elements made by laterally inserting a protrusion, e.g. a rib into a complementarily-shaped groove
- A61F2002/30385—Connections or couplings between prosthetic parts, e.g. between modular parts; Connecting elements made by laterally inserting a protrusion, e.g. a rib into a complementarily-shaped groove the rib and groove having non-parallel, e.g. conically-tapered, cooperating sides, e.g. having a trapezoidal front cross-section
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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
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/30—Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
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- 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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Abstract
The present invention discloses a kind of bone renovating material preparation method and applications with more-dimensional channels structure, and the bone renovating material is made of the basal body structure stacking of at least two stratiforms；Described matrix structure has through hole and a groove, formulated basis material, prefabricated matrix, prepare filler, filling, stacking, sizing, hot-working, heat treatment are made.Bone renovating material prepared by the present invention, by the built-up cubic network passage of the through hole and groove of basal body structure, wherein it is filled with collagenous fibres, be conducive to cell adherence growth and blood vessel and neural to grow into, the transmission of nutriment and the exclusion of cell metabolite are also allowed for, while cell can be made to be uniformly distributed in material internal and be conducive to that internal stent is uniform to be organized the formation of；It is chimeric that firm biology is formed between the structural material energy and freshman bone tissue, good structural stability can be also maintained in degradation process.
Description
Technical field
The invention belongs to field of biomedical materials, it is related to the bone renovating material of clinical practice, more particularly to intensity
The preparation method and applications of the bone renovating material porous with multidimensional and with slow release treatment effect of enhancing.
Background technology
Bone defect is very common disease in clinic, but bone defect healing is still the problem faced in Orthopedic Clinical,
Although scientific worker has done substantial amounts of work in prepared by the research of clinical bone renovating material for many years, make much progress,
But should so there are problems.
The sclerotin of natural bone is divided into compact bone and spongy bone according to the spread pattern of hone lamella and the density difference of space structure,
The fine and close hard anti-pressure anti-torsion Qu Nengli of compact bone is strong, is distributed in the surface of bone, and compact bone has orderly anisotropic structure, main
It is satisfied with its mechanical performance needs.It is more along having of forming of collagenous fibres major axis mineralising that bone tissue is mainly hydroxyapatite
The composite material of pore structure, its structure and mechanical property performance anisotropy.Natural bone is exactly this anisotropic orientation knot
Structure, thus there is optimal mechanical advantage and physiologic function advantage.
It is histiocytic to grow into bone tissue reparation, the generation of new blood vessel, the exchange of nutrition and metabolism thing and stent
The degraded of material requires that repair materials have the porosity and connected ratio of height.The loose structure system of bone renovating material is new
Bone Ingrowth and wound repair necessary requirement, without these loose structures, the material being implanted into cannot complete cell creep and into
Bone alternative Process.Porosity is too low, and surface area is too small, is unfavorable for growing into for tissue, is also unfavorable for the degraded of stent in vivo.Cause
Under the premise of the stability of supporting structure and mechanics is ensured, repair materials should have high porosity and connected ratio for this.Hole it is big
The small activity that can also influence skeletonization, too small aperture, without enough spaces supply cell growth, influence cell secretion matrix and
The infiltration of nutriment.Research shows that 15~50 μm of aperture can induce growing into for fiber tubing, 50~150 μm of aperture
The generation of osteoid tissue can be stimulated, and 150~500 μm of aperture can directly induce the generation of mineralising bone.Too big aperture meeting
Influence the mechanical property of material.Hole is not communicated with making to be connected with each other between new bone, and lacks continuity and conformability.Together
When cell can be made to be uniformly distributed in material internal be conducive to that internal stent is uniform to be organized the formation of.
Although patent CN1325734A, CN101297980A, CN1325734A, CN1647826A, CN103830775A
The bone renovating material prepared using collagen and hydroxyapatite as main material, but it is even poisonous also to add part organic polymer
The organic solvent of property.The shortcomings that universal existing for these materials is：(1) collagenous fiber material or mineralized collagen material are irregular
With orientation irregularly respectively to it is weak to combine power between material molecule, fast without enough mechanical strengths, katabolism, it is impossible to full
Sufficient skeletonization needs；(2) aperture of material is smaller, and connected ratio is low, and common problem is freshman bone tissue only in the outer of stent
Edge is formed, and it is difficult to penetrate into internal stent to make cell, hampers the exchange of internal stent body fluid, and is ultimately resulted in timbering material
The apoptosis of portion's cell, can make be connected with each other between new bone, and lack continuity and conformability, influence the weight of big defect area
Build.(3) there are noxious material residual, it is unfavorable for clinical practice.
Bone renovating material of the present invention is formed by stacking by multilayer material, and every layer of basis material all has certain orientation,
The porous three-dimensional structure of the orientation material can realize the mechanics transmission between bone defect position and normal bone tissues well.Planting
Defect initial stage to the marrow, bone renovating material can provide certain mechanical support for defect.This network can protect
Hole connectivity is demonstrate,proved, is conducive to growing into for cell adherence growth and blood vessel and nerve, also allows for the transmission of nutriment and thin
The exclusion of born of the same parents' metabolin.
When stent starts degraded, the firm biology of formation is chimeric between the structure energy and freshman bone tissue, can also drop
Good structural stability is maintained in solution preocess.As osteocyte and blood vessel are grown into neural, new bone gradually recovers itself
Biomechanical property, while material is also gradually degraded, and catabolite is without any toxicity and side effects, and with the nature of body
Physiological metabolism and excrete, completed reparation and the reconstruction of bone tissue.
The content of the invention
The defects of mechanical property for the artificial bone renovating material of solution is low, and aperture is small and hole Penetration ration is poor, the present invention provides
A kind of bone renovating material preparation method with more-dimensional channels structure, using following technical scheme：
The bone renovating material is made of the basal body structure stacking of at least two stratiforms；Preferred vertical is laminated；
Described matrix structure has through hole and groove；
Step 1：Prepare basis material
Mineralized collagen is mixed with ceramic powder, is stirred, adjusts pH value, electrical conductivity, centrifuges taking precipitate；Add golden yellow Portugal
Grape coccus fermentating liquid filtrate concentrate and collagen, stirring, adjusts pH value, electrical conductivity, vacuum outgas；Adjust conductance
Rate, obtains basis material；
Step 2：Prefabricated matrix
By in the basis material of step 1 preparation in the same direction press-in die, then it is in 30~40 DEG C, relative humidity
Under conditions of more than 90%, 8~12h is aged, obtains prefabricated matrix；
Step 3：Prepare filler
Collagenous fibres are mixed with staphylococcus aureus liquid, are stirred, vacuum outgas, obtains filler；
Step 4：Filling, stacking
The filler that in groove, through hole to the upper and lower surface of the prefabricated matrix of step 2 preparation prepared by filling step three,
Then it is laminated basal body structure material at least more than two layers, obtains layered product；It is preferred that it is laminated more than four layers.
Step 5：Sizing
Layered product prepared by step 4, which is moved into liquid nitrogen, to be freezed to be molded, vacuum freeze drying, isostatic cool pressing contracting；
Step 6：Hot-working
105~125 DEG C of 8~12h of heat treatment, are made sample under nitrogen protective condition.
Stirring of the present invention using stirring in the same direction, it is consistent for stirring clockwise or it is consistent be to stir counterclockwise.
As preferable technical solution, in the step 1, mineralized collagen, collagen, the weight ratio of ceramic powder are 10
~13:1.5~4.5:1~3；The addition of the S. aureus fermentation liquid filtrate is with golden yellow grape in basal body structure
Coccus ferment filtrate 1600~3200 μ g/g of solidification enzymatic activity are meter.
As preferable technical solution, in the step 1, before centrifugation, pH value 7.2~8.0 is adjusted；Before vacuum outgas, adjust
It is 7.2~7.4 to save pH value；Adjust pH value and use phosphoric acid, sodium hydroxide, sodium carbonate or sodium acid carbonate；In the step 1, centrifugation
Before, adjust electrical conductivity and be not more than 1.5ms/cm；Before vacuum outgas, adjust electrical conductivity and be not more than 3.0ms/cm；Conductance after degassing
Rate is adjusted to 5.0~8.0ms/cm, is adjusted electrical conductivity and is used phosphoric acid, sodium hydroxide or sodium carbonate.
As preferable technical solution, in the step 3, collagenous fibres are coagulated with staphylococcus aureus liquid ferment filtrate
Gu the weight ratio of enzymatic activity is 5.0~15:0.12~0.4.
As preferable technical solution, in the step 5, contracted using 200~400MPa isostatic cool pressings.
The present invention also provides the bone renovating material obtained by above-mentioned preparation method with more-dimensional channels structure, described matrix structure
A surface be equipped with several columns boss I, another surface is equipped with several columns boss II；The boss I and boss II are spaced；
Groove is formed between boss II between adjacent boss I, adjacent；Several through holes are equipped with perpendicular to I surface of boss；Institute
Material is stated to be made of the basal body structure stacking at least described in two layers；The groove orientation of adjacent two layers basal body structure is substantially vertical；By
The through hole of layer basal body structure correspondingly connects, easy to form vertical passage；The hole wall of the through hole, which closes on groove, has crack,
The through hole is connected through crack with adjacent groove, and the orientation of through hole and the angle of described matrix structure are 75~90 degree.This hair
The bright passage includes main channel and non-main channel：Main channel is made of groove, through hole；Non- main channel refers to except groove, leads to
The passage that hole possessed by basal body structure beyond hole is formed.
The three-point bending of the bone renovating material with more-dimensional channels structure is strong obtained by above-mentioned preparation method provided by the invention
Degree is more than 40.0Mpa, and compressive strength is more than 51.8Mpa.
As preferable technical solution, the thickness of described matrix structure is 600~1500 μm；The through hole it is a diameter of
180~590 μm；The width of the groove is 180~590 μm, and depth is 180~590 μm.
As preferable technical solution, in each column boss I, the spacing of through hole is 180~590 μm.
As preferable technical solution, the thickness of prefabricated matrix prepared by the step 2 is 8~12mm；Recess width is
2~4mm, depth of groove are 2~4mm；Boss I and II width of boss are 2~4mm；Through-hole diameter is 3~5mm, each column boss I
Middle through hole spacing is 2~4mm.
As preferable technical solution, the ceramic powder includes silica 1~5 of following weight ratio, magnesia 1~5,
Calcirm-fluoride 1~5.
As preferable technical solution, in the step 4, when stacking, communicates inter-level vias, the orientation of through hole with it is described
The angle of basal body structure is 75~90 degree.
As preferable technical solution, contracted in the step 5 using 200~400MPa isostatic cool pressings.
Bone renovating material finished product prepared by the present invention, which grows generous size, to be made choice according to clinic needs, preferably length and width
No more than 5.0cm, thickness is no more than 1.0cm, or carries out the processing of material profile, can also carry out fragmented processing, so as to
Filling for micropore.
Above-mentioned gained provided by the invention have more-dimensional channels structure bone renovating material application, for repair of fractured bones,
Bone defect healing or filling, bone is orthopedic, bone grafting merges or joint prosthesis replaces or overhaul middle bone defect.
As preferable technical solution, the fracture includes closed or open fracture；The bone defect includes congenital
Property bone is abnormal, bone defect after neoplastic lesion excision；Bone grafting fusion is included between spinal vertebral, phalanx fusion between vertebral plate；It is described
Bone defect filling includes the bone defect filling of cavity section.
Advantages of the present invention：
Bone renovating material provided by the invention, by the built-up cubic network passage of the through hole and groove of basal body structure,
Collagenous fibres are wherein filled with, is conducive to cell adherence growth and blood vessel and neural and grows into, also allow for the biography of nutriment
The exclusion with cell metabolite is passed, while cell can be made to be uniformly distributed in material internal and be conducive to uniform group of internal stent
Knit to be formed；It is chimeric that firm biology is formed between the structural material energy and freshman bone tissue, also can remain good in degradation process
Good structural stability；The bone renovating material mechanical strength prepared using the method is high, can realize well bone defect position with
Mechanics transmission between normal bone tissues.At implantation bone defect position initial stage, bone renovating material can provide necessarily for defect
Mechanical support；Bone renovating material degradation time is grown, and consistent with the generation of freshman bone tissue, beneficial to damaged bone tissue reparation.
The present invention using by sample carries out up to 200~400MPa isostatic cool pressings processing, basal body structure after overcompression,
The distance between molecule diminishes, and the active force between Van der Waals force, hydrogen bond equimolecular is stronger, particularly across material after hot dehydrogenation crosslinking
The intensity bigger of material；The aperture of collagenous fibres body is 130~450 μm in material；Micropore occupation rate is 60~90%.Realize
The three-dimensional hole connectivity structure of real meaning, and this aperture structure is adapted to growing into for cell, and cell can be made equal in material internal
Even be distributed with organizes the formation of beneficial to internal stent is uniform.
The component ratio of collagen and hydroxyapatite and nature bone are basically identical in material.The pottery that basal body structure uses
Porcelain powder is inorganic porous material, not only to the inducing action that is grown with of cell, is also had to the mechanical strength for improving bone renovating material
Positive effect, avoids the too fast degraded of material.
All containing the S. aureus fermentation liquid filtrate for promoting fracture to have Healing in matrix and filler.It is golden yellow
The main component of color Staphylococcal fermentation liquid filtrate is protein, polypeptide, 18 kinds of amino acid, free coagulases.Main pharmacological
Effect is to promote union, treats osteoporosis.In clinical practice mainly intramuscular injection, effect are carried out in diseased region
Very well, but side effect is phenomena such as causing local swelling sense, pain, fever, to allow patient to produce repulsion.The handle of the invention
S. aureus fermentation liquid filtrate is added in bone renovating material, keeps S. aureus fermentation liquid filtrate in material
Middle sustained release, plays its unique pharmacological action, golden in collagenous fibres in advance with the infiltration of tissue fluid and the degraded of material
The pharmaceutical component of staphylococcus aureus fermentating liquid filtrate is first quickly discharged, and the pharmaceutical component in subsequent basis material is with base
The decomposition of body material carries out follow-up sustained release, plays long-acting.
Brief description of the drawings
4 width of attached drawing of the present invention,
Fig. 1 is bone renovating material structure diagram of the present invention；
Fig. 2 is the scanning electron microscope (SEM) photograph that embodiment 4 prepares sample；
The non-main channel section scanning electron microscope image of Fig. 3 bone renovating materials, the visible bone renovating material from scanning figure
Structure be multi-C stereo, non-main channel section aperture is 30-180 μm, and micropore occupation rate is 85%；
Pore-size distribution in Fig. 4 bone renovating materials main channel, it is seen that the aperture of collagenous fibres is mainly 130- in main channel
450μm；
In figure, 1 basal body structure；2 boss I；3 boss II；4 grooves；5 through holes；6 cracks.
Embodiment
Following non-limiting examples can make those of ordinary skill in the art be more fully understood the present invention, but not with
Any mode limits the present invention.
Invention effect can be achieved using art technology versatile material in raw material of the present invention, is below preferable for embodiment
Pretreatment of raw material scheme：
1. mineralized collagen material：Preparation method is referring to Masanori Kikuchi, Soichiro Itoh, ect.Self-
organization mechanism in a Bone-Like Hydroxyapatite/Collagen Nanocomposite
synthesized in vitro and Its Biological Raction in vivo.Biomaterials 22(2001)
1705-1711.Wherein Ca:P=1~2:1, hydroxyapatite:Collagen=4:0.8~1.2, the c-axis of hydroxyapatite and
Collagenous fibres length is parallel, and electrical conductivity is less than 20us/cm, water content 80% (g/g).
2. ceramic powder：It will be mixed by weight silica 1~5, magnesia 1~5, calcirm-fluoride 1~5 with polylactic acid, into
Type, 200 DEG C of drying, then calcines 5h at 1100~1300 DEG C, and particle diameter is ground into after cooling as 80~300 μm, aperture for 60~
210 μm, porosity is more than 80%, and partial hole is the cell structure communicated.
3. S. aureus fermentation liquid filtrate：The golden yellow of commercially available (reaching biochemical Pharma Inc. purchased from Changchun profound scholar)
Staphylococcal fermentation liquid filtrate uses ultrafiltration membrane ultrafiltration of the molecular cut off for 20000 dalton, and film top is divided into containing coagulase
Concentrate, then 40 DEG C of cryogenic vacuum concentrations of warp -0.098MPa prepare S. aureus fermentation liquid filtrate solidification enzymatic activity not
Less than the concentrate of 3200 μ g/ml.
4. collagenous fibres：
A. it is 20mM acetic acid or phosphorus ox heel string and/or the I collagens of horse heel string that purity is more than 99.5% to be dissolved in concentration
In acid solution, collagen concentration 2.0g/L, lye, concentration 70mM are added dropwise into collagen solution, and keep 10mM Mg2+、20mM
K+、20mM HPO4 3+Ion, pH value 7.0.Collagenous fibres are obtained, are aged 4h, then centrifuge 30min in 4 DEG C of 6000rpm, are collected
Collagenous fibres precipitate, water content 85% (g/g).
The mould that embodiment 1-4 is used to suppress basal body structure is processed according to lower structure：
Matrix has the basal body structure 1 of stratiform；One surface of described matrix structure 1 is equipped with several columns boss I 2, another
Surface is equipped with several columns boss II 3；The boss I 2 and boss II 3 are spaced；Between adjacent boss I 2, adjacent boss
Groove 4 is formed between II 3；Several through holes 5 are equipped with perpendicular to I 2 surface of boss.Material is as the matrix described at least two layers
The stacking of structure 1 is formed；The groove 4 of adjacent two layers basal body structure 1 is orientated substantially vertical；Successively the through hole 5 of basal body structure 1 is correspondingly
Connection.The hole wall of through hole 5, which closes on, has crack 6 at groove 4, the through hole 5 is connected through crack 6 with adjacent groove 4.
Embodiment 1
It is prepared by bone renovating material
Step 1 prepares basis material
50g mineralized collagens material (water content 80%) is weighed, adds ceramic powder 2g thereto, it is suitable with the rotating speed of 100rpm
Hour hands stir evenly, and pH value is adjusted to 7.0 with 1.0M phosphoric acid liquids and 1.0M sodium hydroxide lyes, then molten with 0.5M sodium carbonate
Liquid adjusts pH value to 7.2, electrical conductivity 1.5ms/cm.4 DEG C of centrifugation 30min of static 30min, 10000rpm remove supernatant.To
S. aureus fermentation liquid filtrate is added in precipitation, it is 1600 μ g/g to make solidification enzymatic activity, adds 37.5g collagens
Material (purity of collagen is 40mg/g), continues same direction uniform stirring, and adjust precipitation to make compound mineralization collagen-based
The pH value of body is 7.2, electrical conductivity 3.0ms/cm.More than 1.01 × 102Deaerate under Pa vacuum conditions, be further continued for using 1.0M
Phosphoric acid liquid and 1.0M sodium hydroxide lyes, which are adjusted, makes electrical conductivity be 7.0ms/cm.
The prefabricated matrix of step 2 (basal body structure for preparing the stratiform before compression)
The basis material of preparation is complied with the press-in die of direction to same, the thickness for making prefabricated matrix is 8mm；, groove
Depth is 2mm, recess width 2mm；The boss I and wide 2mm of boss II；Through-hole aperture 3mm, Fracture Width 1mm；Each column is convex
Through hole spacing is 2mm in platform I.Then at 30 DEG C, relative humidity is aged 12h under conditions of being more than 90%, obtains prefabricated matrix.
Step 3 prepares filler
Weigh collagenous fibres addition water and be diluted to 15mg/g, add S. aureus fermentation liquid filtrate thereto, make
S. aureus fermentation liquid filtrate coagulation activity is 400 μ g/g, is sequentially stirred evenly, 1.01 × 103It is true under Pa pressure
Sky degassing.
Step 4 filling, stacking
The filler that in the groove and through hole of the prefabricated matrix upper and lower surface prepared to step 2 prepared by filling step three；Fill out
The lateral opposite side levels of Shi Congyi are filled to spread into or be filled with；Then the three-dimensional prefabricated matrix of stacking is carried out, the matrix number of plies is 4 layers, stacking
When communicate inter-level vias, through hole and basis material planar shaped are angled 75~90 degree, obtain layered product.
Step 5 is shaped
Layered product prepared by step 4 freezes to be molded according to slowly moving into liquid nitrogen perpendicular to liquid level direction, then vacuum
Freeze-drying, when product moisture content is 10~15% (g/g), carries out the isostatic cool pressing contracting of 200MPa, is then further continued for true
Sky drying to moisture is less than 5%.
After compression, bone renovating material thickness is 4000 μm；Non- main channel section aperture is 30~180 μm, main channel section
Aperture is 130~450 μm.
Step 6 hot-working
Material is subjected to the lower 110 DEG C of crosslinkings 10h of high pure nitrogen protective condition, product is made.
Embodiment 2
Step 1 prepares basis material
65g mineralized collagens material (water content 80%) is weighed, adds ceramic powder 2g thereto, it is suitable with the rotating speed of 100rpm
Hour hands stir evenly, and then pH value are adjusted to 7.0 with 1.0M phosphoric acid liquids and 1.0M sodium hydroxide lyes, then with 0.5M sodium carbonate
Solution adjusts pH value to 7.2, electrical conductivity 1.5ms/cm.4 DEG C of centrifugation 30min of static 30min, 10000rpm remove supernatant.
S. aureus fermentation liquid filtrate is added into precipitation, it is 3200 μ g/g to make solidification enzymatic activity, adds 75g collagens
Material (purity of collagen is 40mg/g), continues same direction uniform stirring, and adjust precipitation to make compound mineralization collagen-based
The pH value of body is 7.2, electrical conductivity 3.0ms/cm.More than 1.01 × 102Deaerate under Pa vacuum conditions, be further continued for using 1.0M
Phosphoric acid liquid and 1.0M sodium hydroxide lyes, which are adjusted, makes electrical conductivity be 7.0ms/cm.
The prefabricated matrix of step 2 (basal body structure for preparing the stratiform before compression)
Basis material will be prepared to comply with the press-in die of direction to same, the thickness for making prefabricated matrix is 9mm；, groove depth
Spend for 4mm, recess width 3mm；The boss I and wide 3mm of boss II；Through-hole aperture 4mm, Fracture Width 1mm；Each column boss I
Middle through hole spacing is 3mm.Then at 30 DEG C, relative humidity is aged 12h under conditions of being more than 90%, obtains prefabricated matrix.
Step 3 prepares filler
Weigh collagenous fibres addition water and be diluted to 10mg/g, add S. aureus fermentation liquid filtrate thereto, make
S. aureus fermentation liquid filtrate coagulation activity is 400 μ g/ml, is sequentially stirred evenly, 1.01 × 103It is true under Pa pressure
Sky degassing.
Step 4 filling, stacking
Upper and lower surface, groove and the through hole filler of the prefabricated matrix prepared to step 2 are horizontal from a lateral opposite side
Spread into or be filled with；Then carry out it is three-dimensional be laminated prefabricated matrix, the basis material number of plies is 4 layers, and when stacking communicates inter-level vias, leads to
Hole and basis material planar shaped are angled 75~90 degree, obtain layered product.
Step 5 is shaped
Layered product prepared by step 4 freezes to be molded according to slowly moving into liquid nitrogen perpendicular to liquid level direction, then vacuum
Freeze-drying, when product moisture content is 10~15% (g/g), carries out the isostatic cool pressing contracting of 200MPa, is then further continued for true
Sky drying to moisture is less than 5%.
After compression, bone renovating material thickness is 4000 μm；Non- main channel section aperture is 30~180 μm, main channel section
Aperture is 130~450 μm.
Step 6 hot-working
Material is subjected to the lower 105 DEG C of crosslinkings 12h of high pure nitrogen protective condition, product is made.
Embodiment 3
Step 1 prepares basis material
50g mineralized collagens material (water content 80%) is weighed, adds ceramic powder 1g thereto, it is suitable with the rotating speed of 100rpm
Hour hands stir evenly, and then pH value are adjusted to 7.0 with 1.0M phosphoric acid liquids and 1.0M sodium hydroxide lyes, then with 0.5M sodium carbonate
Solution adjusts pH value to 7.2, electrical conductivity 1.5ms/cm.4 DEG C of centrifugation 30min of static 30min, 10000rpm remove supernatant.
S. aureus fermentation liquid filtrate is added into precipitation, it is 1600 μ g/g to make solidification enzymatic activity, adds 75g collagens
Material (purity of collagen is 40mg/g), continues same direction uniform stirring, and adjust precipitation to make compound mineralization collagen-based
The pH value of body is 7.2, electrical conductivity 3.0ms/cm.More than 1.01 × 102Deaerate under Pa vacuum conditions, be further continued for using 1.0M
Phosphoric acid liquid and 1.0M sodium hydroxide lyes, which are adjusted, makes electrical conductivity be 8.0ms/cm.
The prefabricated matrix of step 2 (basal body structure for preparing the stratiform before compression)
The basis material of preparation is complied with the press-in die of direction to same, it is 8mm to make prefabricated matrix thickness；, groove depth
Spend for 2.5mm, recess width 2.5mm；The boss I and wide 2.5mm of boss II；Through-hole aperture 3.5mm, Fracture Width 1mm；Often
Through hole spacing is 2.5mm in row boss I；.Then at 30 DEG C, relative humidity is aged 12h under conditions of being more than 90%, obtains prefabricated
Matrix.
Step 3 prepares filler
Weigh collagenous fibres addition water and be diluted to 8mg/g, add S. aureus fermentation liquid filtrate thereto, make gold
Staphylococcus aureus fermentating liquid filtrate coagulation activity is 400ug/g, is sequentially stirred evenly, 1.01 × 103Pa vacuum under pressure
Degassing.
Step 4 filling, stacking
The groove and through hole filler of the upper and lower surface of the prefabricated matrix prepared to step 2 are from a lateral opposite side water
Tile into or be filled with；Then the three-dimensional prefabricated matrix of stacking is carried out；The basis material number of plies is 4 layers, and when stacking communicates inter-level vias,
Through hole and basis material planar shaped are angled 75~90 degree, obtain layered product.
Step 5 is shaped
Layered product prepared by step 4 freezes to be molded according to slowly moving into liquid nitrogen perpendicular to liquid level direction, then vacuum
Freeze-drying, when product moisture content is 10~15% (g/g), carries out the isostatic cool pressing contracting of 200MPa, is then further continued for true
Sky drying to moisture is less than 5%.
After compression, bone renovating material thickness is 4000 μm；Non- main channel section aperture is 30~180 μm, main channel section
Aperture is 130~450 μm.
Step 6 hot-working
Material is subjected to the lower 110 DEG C of crosslinkings 10h of high pure nitrogen protective condition, product is made.
Embodiment 4
Step 1 prepares basis material
65g mineralized collagens material (water content 80%) is weighed, adds ceramic powder 3g thereto, it is suitable with the rotating speed of 100rpm
Hour hands stir evenly, and then pH value are adjusted to 7.0 with 1.0M phosphoric acid liquids and 1.0M sodium hydroxide lyes, then with 0.5M carbonic acid
Sodium solution adjusts pH value to 7.2, electrical conductivity 2.5ms/cm.4 DEG C of centrifugation 30min of static 30min, 10000rpm remove supernatant
Liquid.S. aureus fermentation liquid filtrate is added into precipitation, it is 3200 μ g/g to make solidification enzymatic activity, adds 112.5g glue
Former protein material (purity of collagen is 40mg/g), continues same direction uniform stirring, and adjust precipitation to make compound mineralization
The pH value of collagen matrices is 7.2, electrical conductivity 3.0ms/cm.More than 1.01 × 102Deaerate, be further continued under Pa vacuum conditions
Being adjusted with 1.0M phosphoric acid liquids and 1.0M sodium hydroxide lyes makes electrical conductivity be 10.0ms/cm.
The prefabricated matrix of step 2 (basal body structure for preparing the stratiform before compression)
The basis material of preparation is complied with the press-in die of direction to same, it is 9mm to make prefabricated matrix thickness；, groove depth
Spend for 4mm, recess width 4mm；The boss I and wide 4mm of boss II；Through-hole aperture 5mm, Fracture Width 1mm；Each column boss I
Middle pitch of holes is 4mm.Then at 30 DEG C, relative humidity is aged 12h under conditions of being more than 90%, obtains prefabricated matrix.
Step 3 prepares filler
Weigh collagenous fibres addition water and be diluted to 5mg/g, add S. aureus fermentation liquid filtrate thereto, make gold
Staphylococcus aureus fermentating liquid filtrate coagulation activity is 400ug/g, is sequentially stirred evenly, 1.01 × 103Pa vacuum under pressure
Degassing.
Step 4 filling, stacking
The groove and through hole filler of the upper and lower surface of the prefabricated matrix prepared to step 2 are from a lateral opposite side water
Tile into or be filled with, then carry out the three-dimensional prefabricated matrix of stacking；The basis material number of plies is 4 layers, and upper lower opening corresponds during lamination,
Obtain layered product.
Step 5 is shaped
Layered product prepared by step 4 freezes to be molded according to slowly moving into liquid nitrogen perpendicular to liquid level direction, then vacuum
Freeze-drying, when product moisture content is 10~15% (g/g), carries out the isostatic cool pressing contracting of 200MPa, is then further continued for true
Sky drying to moisture is less than 5%.
After compression, bone renovating material thickness is 4200 μm；Non- main channel section aperture is 30~180 μm, main channel section
Aperture is 130~450 μm.
Step 6 hot-working
Material is subjected to the lower 125 DEG C of crosslinkings 8h of high pure nitrogen protective condition, sample is made.
As a result detect
1 bending strength detects
Bone renovating material sample is prepared according to embodiment 1, the sample number of plies is 4 layers, and after 200Mpa compressions, a length of 20mm is wide
10mm, thickness 4.0mm.Sample is subjected to three-point bending detection with 5569 Apparatus for Bending at low-temp of Instron (instron), by span
15mm, loading velocity 3mm/min are arranged to, after sample is loaded, load and displacement are returned to zero, load is arranged to 1000N.It is real
Test speed and be arranged to 3mm/min, click on the operation button on computer interface, carry out bend test, testing result is as follows：
The bending strength testing result of table a sample
2 compressive strengths detect
Bone renovating material sample is prepared according to embodiment 4, the sample number of plies is 4 layers, and after 200Mpa compressions, a length of 20mm is wide
10mm, thickness 4.2mm, intensity detection experiment, compression strength are carried out by sample with Instron (instron) 5500R testing machines
The maximum pressure born by unit area during sample deformation 1mm, compression speed 0.3mm/min, testing result are as follows：
The compressive strength testing result of two sample of table
3 product structures detect
Sample is prepared according to embodiment 4, and the sample number of plies is 4 layers, and after 200Mpa compressions, a length of 20mm, wide 10mm, thickness is
4.2mm.By sample metal spraying, with scanning electron microscope EVO18 (SEM)) carry out micro-structure scanning, non-main channel section scanning figure
Spectrum is shown in Fig. 3, and bone renovating material main channel section aperture ratio is shown in Fig. 4.
Claims (7)
- A kind of 1. bone renovating material preparation method with more-dimensional channels structure, it is characterised in that：The bone renovating material is made of the basal body structure stacking of at least two stratiforms；Described matrix structure has through hole and groove；Step 1：Prepare basis materialMineralized collagen is mixed with ceramic powder, is stirred, adjusts pH value, electrical conductivity, centrifuges taking precipitate；Add Staphylococcus aureus Fermented liquid filtrate concentrate and collagen, stirring, adjusts pH value, electrical conductivity, vacuum outgas；Electrical conductivity is adjusted, is obtained Basis material；Step 2：Prefabricated matrixBasis material prepared by step 1 is in the same direction in press-in die, then in 30~40 DEG C, relative humidity 90% Under conditions of above, 8~12h is aged, obtains prefabricated matrix；Step 3：Prepare fillerCollagenous fibres are mixed with staphylococcus aureus liquid, are stirred, vacuum outgas, obtains filler；Step 4：Filling, stackingThe filler that in groove, through hole to the upper and lower surface of the prefabricated matrix of step 2 preparation prepared by filling step three, then It is laminated basal body structure material at least more than two layers, obtains layered product；Step 5：SizingLayered product prepared by step 4, which is moved into liquid nitrogen, to be freezed to be molded, vacuum freeze drying, isostatic cool pressing contracting；Step 6：Hot-working105~125 DEG C of 8~12h of heat treatment, are made sample under nitrogen protective condition；One surface of described matrix structure (1) is equipped with several columns boss I (2), and another surface is equipped with several columns boss II (3)； The boss I (2) and boss II (3) are spaced；Formed between boss II (3) between adjacent boss I (2), adjacent recessed Groove (4)；Several through holes (5) are equipped with perpendicular to described I (2) surface of boss；The material is as the matrix knot described at least two layers Structure (1) stacking is formed；Groove (4) orientation of adjacent two layers basal body structure (1) is substantially vertical；The successively through hole of basal body structure (1) (5) correspondingly connect；The hole wall of the through hole (5), which closes on groove (4) place, has crack (6), and the through hole (5) is through crack (6) Connected with adjacent groove (4), the orientation of through hole and the angle of described matrix structure are 75~90 degree.
- 2. the preparation method of the bone renovating material according to claim 1 with more-dimensional channels structure, it is characterised in that：Institute State in step 1, mineralized collagen, collagen, the weight ratio of ceramic powder are 10~13:1.5~4.5:1~3；The golden yellow The addition of Staphylococcal fermentation liquid filtrate is with 1600~3200 μ g/g of staphylococcus aureus coagulase activity in basal body structure For meter.
- 3. the preparation method of the bone renovating material according to claim 1 with more-dimensional channels structure, it is characterised in that：Institute State in step 1, before centrifugation, adjust pH value 7.2~8.0；Before vacuum outgas, it is 7.2~7.4 to adjust pH value；PH value is adjusted to use Phosphoric acid, sodium hydroxide, sodium carbonate or sodium acid carbonate；In the step 1, before centrifugation, adjust electrical conductivity and be not more than 1.5ms/cm；Before vacuum outgas, adjust electrical conductivity and be not more than 3.0ms/cm；Electrical conductivity is adjusted to 5.0~8.0ms/cm after degassing, is adjusted electrical conductivity and is used phosphoric acid, sodium hydroxide or carbonic acid Sodium.
- 4. the preparation method of the bone renovating material according to claim 1 with more-dimensional channels structure, it is characterised in that：Institute State in step 3, the weight ratio of collagenous fibres and staphylococcus aureus liquid is 5.0~15:0.12~0.4.
- 5. the preparation method of the bone renovating material according to claim 1 with more-dimensional channels structure, it is characterised in that：Institute State in step 5, contracted using 200~400MPa isostatic cool pressings.
- 6. having the bone renovating material of more-dimensional channels structure obtained by any one of them preparation method of claim 1-5, it is special Sign is：The three-point bending strength of the bone renovating material is more than 40.0Mpa, and compressive strength is more than 51.8Mpa.
- 7. the preparation method of the bone renovating material according to claim 1 with more-dimensional channels structure, it is characterised in that：Institute The thickness for stating the prefabricated matrix of step 2 preparation is 8~12mm；Recess width is 2~4mm, and depth of groove is 2~4mm；Boss I (2) it is 2~4mm with boss II (3) width；Through-hole diameter is 3~5mm, and through hole spacing is 2~4mm in each column boss I.
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