CN106492281A - A kind of biocompatibility bone graft and preparation method thereof - Google Patents

A kind of biocompatibility bone graft and preparation method thereof Download PDF

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Publication number
CN106492281A
CN106492281A CN201611047558.0A CN201611047558A CN106492281A CN 106492281 A CN106492281 A CN 106492281A CN 201611047558 A CN201611047558 A CN 201611047558A CN 106492281 A CN106492281 A CN 106492281A
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bone graft
biocompatibility
cartilage
preparation
calcium salt
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CN106492281B (en
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赵应征
鲁翠涛
徐荷林
陈翩翩
诸葛德力
杨靖靖
许洁
范子梁
金冰慧
沈碧欣
朱群燕
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Wenzhou Medical University
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Wenzhou Medical University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02Inorganic materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02Inorganic materials
    • A61L27/12Phosphorus-containing materials, e.g. apatite
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/16Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3604Materials 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
    • A61L27/3608Bone, e.g. demineralised bone matrix [DBM], bone powder
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3604Materials 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
    • A61L27/3612Cartilage, synovial fluid
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    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3641Materials 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
    • A61L27/3645Connective tissue
    • A61L27/365Bones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials 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
    • A61L27/3683Materials 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
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    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
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    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412Tissue-regenerating or healing or proliferative agents
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    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/02Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

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Abstract

The present invention provides a kind of biocompatibility bone graft, the key component of the support includes fibroin albumen, polyvinyl alcohol, calcium salt, the cartilage Acellularized valve composition of Amphibian and Osteoinductive Factor, can pass through to change component proportion, control the mechanical strength and degradation speed of bone graft.The biocompatibility bone graft is in threedimensional solid shape, and with good mechanical characteristic, the fine and closely woven cavity of surface distributed is conducive to sticking and regenerating for chondrocyte.This biocompatibility bone graft preparation process is not heated, does not use any chemistry or enzyme crosslinking agent, saves the activity of each component.This biocompatibility bone graft plays the collaboration advantage of various components, is applied to the replacement graft of osseous tissue defect.

Description

A kind of biocompatibility bone graft and preparation method thereof
Technical field
The present invention relates to medical science bone collection field of engineering technology, and in particular to a kind of have regenerability and preferable mechanics strong Biocompatibility bone graft of degree and preparation method thereof.
Background technology
Itself repair ability of skeleton is extremely limited, and it is to repair bone defects to build through engineering approaches skeleton with tissue engineering technique Provide a kind of method with applications well prospect.It is multi-party that the research contents of bony site implantation is related to material, preparation, transplantation medicine Face subject technology, the biocompatibility bone graft wherein built preferably with regenerability and preferable mechanical strength is successfully Key.
Timbering material currently used for bony site implantation engineering includes two kinds of natural material and synthetic material, synthetic Material mainly have PGA, polylactide and both copolymers etc..The shortcoming of synthetic material is hydrophobicity, no Beneficial to the adhesion of cell, and catabolite easily causes inflammatory reaction in vivo in acidity.And natural material derives from animal Or human body, the growth of the suitable seed cell of its network structure, composition, biomechanical environment, development and metabolism, material can drop Solution, is therefore increasingly paid attention to by researcher.
Conventional natural bone grafting material has the biomimetic scaffolds of collagen and hyaluronan for the natural cartilage of raw material at present.My god So the basic principle of material development is bionical, that is, simulate structure and the biochemical composition of nature bone extracellular matrix, be skeletonization Cell growth provides control environment.But osteoblast epimatrix biochemical component and complex structure, biomimetic material are difficult to real mould The natural structure of the complexity of bone-imitation tissue, biomechanicss and biological characteristicses, seldom enter clinical practice, there is no preferable bone to move Plant holdfast.
Acellular matrix causes the material of immunoreation due to eliminating cell and soluble protein etc., and remains original First natural structure, has been obtained for being widely applied.At present, acellular dermal matrix in implant therapy commercialization.External someone Rabbit nose interval cartilage is inactivated with methods such as dehydration of alcohol, lyophilizing and liquid nitrogen circulating freezing resistances, as the support of cell growth, But this kind of method remains can cell debris, antigenicity is removed not thoroughly, and the bulk cartilage for inactivating is tied without holey Structure, cytotrophy supply and metabolic waste are discharged difficult.The country has carries out the research report that de- cell is processed by cartilage monoblock, But the de- cellular cartilage for being formed does not possess tissue engineering bracket requirement and obtains porous network structure, the transmission and metabolism of nutrient substance Thing sends difficulty;In addition the country have cartilage is crushed after cell free research report, cartilage crushed by Han Xuefeng et al. Into 100~154 μm of microgranules, tissue engineered bone is built with chondrocyte mixed culture, which has the disadvantage that microgranule is larger and chondrocyte Mixing is uneven, and does not possess certain specific shape, and cell-composite material of particles biomechanical strength is low, and operation is implanted into not Easy to operate, easily occur the problems such as deforming after transplanting.
Fibroin albumen is the natural polymer fibrin extracted from silkworm silk, and content accounts for the 70%~80% of silkworm silk, Be rich in 18 kinds of aminoacid, with excellent physical characteristics and chemical characteristic, can by different disposal obtain fiber, powder, film, The material of the various traits such as gel.The rise that studies recently as engineered organ and cytoskeleton and various biologies The development of technology, the application of fibroin albumen are more and more extensive, have been successfully applied in multiple medical materials such as operation suture thread, but It is that fibroin albumen itself does not have promotion regenerating bone or cartilage ability.Additionally, cell culture experiments in vitro finds that surface scribbles fibroin egg In white culture dish, cell is difficult to stick, poor growth.Therefore, although fibroin albumen has preferable elastic strength, wearability The mechanical characteristics such as energy, but lack promotion cell adhesion and regeneration capacity, therefore it is difficult to apply in bone graft.
The material for being preferably used for bone collection should meet following basic demand:1. there is good elastic strength, wearability The mechanical characteristics such as energy, can be matched with the mechanical requirements of tissue implant site.2. have and be suitable for cell adhesion, hypertrophy and differentiation Surface chemistry, is conducive to osteoblast to adhere to.3. immediate extracellular microenvironment is provided for Oesteoblast growth, good Good biocompatibility and Bioabsorbable.4. preparation flow is simple, and the bone graft product for preparing is easily long-term Preserve.
Content of the invention
In order to overcome the defect of prior art, it is an object of the invention to provide a kind of have regenerability and elastic strength Biocompatibility bone graft, the defect repair of clinically skeleton can be used in conjunction with transplant operation.
Another object of the present invention is to providing the preparation method of above-mentioned biocompatibility bone graft.
By many experiments, the present invention is using the fibroin albumen of good biocompatibility and excellent mechanical property as substrate Material, in conjunction with the polyvinyl alcohol with good adhesion, provides the calcium salt of bone cell growth environment, promotes the two of osteanagenesiss Dwell animal cartilage Acellularized valve and Osteoinductive Factor, prepare and form a kind of biocompatibility bone collection for meeting desirable Thing.
A kind of key component of biocompatibility bone graft of the present invention includes:Fibroin albumen, polyvinyl alcohol, calcium salt, The cartilage Acellularized valve composition of Amphibian and Osteoinductive Factor, can pass through to change component proportion, control bone graft Mechanical strength and degradation speed.
In above-mentioned biocompatibility bone graft, the weight/mass percentage composition of fibroin albumen is 10%-30%, polyvinyl alcohol Weight/mass percentage composition be 1%-5%, the weight/mass percentage composition of calcium salt be that 20%-50%, the cartilage of Amphibian remove cell It is 0.1%-10% that the weight/mass percentage composition that puts up point is 20%-50%, the weight/mass percentage composition of Osteoinductive Factor.
Above-mentioned calcium salt includes hydroxyapatite, calcium sulfate, calcium citrate, calcium phosphate, halobiontic bone shell and its carries Take thing.
Can the water of crystallization containing varying number in above-mentioned calcium salt structure.
Above-mentioned Osteoinductive Factor includes that chondroitin sulfate, hyaluronic acid, collagen, the biology of promotion bone growth are lived Sex factor one or more.
A kind of preparation method of above-mentioned biocompatibility bone graft, by the cartilage Acellularized valve powder of Amphibian Broken, mix with calcium salt, fibroin albumen and Osteoinductive Factor, add polyvinyl alcohol ethanol solution, mix, form uniform half solid Body, is placed in drying and moulding in metal die, forms the three-dimensional tubulose bone graft containing hollow duct, gamma-radiation irradiation sterilization.
The cartilage of described Amphibian is removed cell by the preparation method of another kind of above-mentioned biocompatibility bone graft Support is crushed, and is mixed with calcium salt and fibroin albumen, is added polyvinyl alcohol ethanol solution, mixes, and formation is uniform semi-solid, is placed in gold Category mould in drying and moulding, formed containing hollow duct three-dimensional tubulose bone graft, by soak or coating method will containing into The solution of bone-inducing factor is distributed in the inner chamber of three-dimensional tubulose bone graft and surface, is formed with glutinous beneficial to chondrocyte after drying Echo the Osteoinductive Factor coating of regeneration, gamma-radiation irradiation sterilization.
Further add in the preparation process of above-mentioned biocompatibility bone graft the pH buffer conventional for pharmacy, Antioxidant, surfactant.
Above-mentioned biocompatibility bone graft is used for the replacement graft of osseous tissue defect.
The biocompatibility bone graft of the present invention possesses advantages below:1. the cartilage Acellularized valve of Amphibian is applied Composition prepares biocompatibility bone graft, not only wide material sources, and good biocompatibility, and has promotion osteanagenesiss Ability.2. application fibroin albumen and polyvinyl alcohol, remove the immunoreation caused because of sericin, keep bone graft to have good The mechanical characteristics such as elastic strength well, anti-wear performance, can be matched with the mechanical requirements of osseous tissue implant site.3. osteogenic induction The cartilage Acellularized valve composition of the factor, calcium salt and Amphibian is shared, and is provided for bone growth immediate extracellular Microenvironment, with the characteristic for promoting cell adhesion, hypertrophy and differentiation, is conducive to osteocyte attachment regeneration.4. bone graft has Good biocompatibility and Bioabsorbable.5. preparation flow is simple, the biocompatibility bone graft for preparing Aseptic, easily long-term preservation;Surface is distributed fine and closely woven hole, is conducive to sticking for osteocyte into hydrophilic.6. biocompatibility Bone graft preparation process is not heated, does not use any chemistry or enzyme crosslinking agent, caused by will not producing because of cross-linking agent residual Toxicity, also saves the activity of each component.
Specific embodiment
The specific embodiment of the invention is discussed in detail below.It should be noted that the technology described in following embodiments is special Levy or the combination of technical characteristic is not construed as isolated, they can be mutually combined so as to reaching superior technique Effect.
Embodiment 1 has the preparation of the biocompatibility bone graft of regenerability and elastic strength
Preparation method 1:According to each experimental group of the biocompatibility bone graft of table 1 and the composition of matched group, each group is weighed Point, the cartilage Acellularized valve of Amphibian is crushed, is mixed with calcium salt, fibroin albumen and Osteoinductive Factor, add poly- second Enol ethanol solution, mixes, and forms uniform semisolid, is placed in drying and moulding in metal die, forms the three-dimensional containing hollow duct Tubulose bone graft, gamma-radiation irradiation sterilization.
Preparation method 2:According to each experimental group of the biocompatibility bone graft of table 1 and the composition of matched group, each group is weighed Point, the cartilage Acellularized valve of Amphibian is crushed, is mixed with calcium salt and fibroin albumen, is added polyvinyl alcohol ethanol solution, Mix, form uniform semisolid, be placed in drying and moulding in metal die, form the three-dimensional tubulose bone graft containing hollow duct, Inner chamber and the surface that the solution containing Osteoinductive Factor is distributed in by immersion or coating method for three-dimensional tubulose bone graft, The Osteoinductive Factor coating that sticks beneficial to chondrocyte and regenerate, gamma-radiation irradiation sterilization is formed with after drying.
The composition of each experimental group of 1 biocompatibility bone graft of table
Note:"/" represents this group and is divided into 0;Under " cartilage Acellularized valve composition " item numeral after bracket in animal be Refer to the source animal of cartilage Acellularized valve composition.
The performance detection and application effect of 2 biocompatibility bone graft of embodiment
(1) performance detection of each group bone graft
Surface apertures are observed:The porosity of the biocompatibility osteograft surface of each group under light microscopic and scanning electron microscopic observation And pore size, if uniformity.
Water absorption is determined:Biocompatibility bone graft quality Wo value is weighed, the weighing for filling deionized water is subsequently placed in In bottle, fully swelling, surface moisture is blotted with filter paper, claim quality to obtain Wn values.Sample water absorption rate is calculated according to following equation:Water suction Rate (%)=[(Wn-Wo)/Wo] × 100
Hardness measurement:Using universal testing machine, modulus of compressibility and the stretch moduluses of biocompatibility bone graft are determined.
(2) biocompatibility of each group bone graft
Toxicity of the biocompatibility bone graft lixiviating solution to the various kinds of cell of In vitro culture is detected using mtt assay;Using Biocompatibility bone graft is implanted to nude mice back sack made by leather, takes structure observation result, judge support after 4 weeks by experiment of nude mouse The internal compatibility.
(3) skin grafing and mending effect of each group bone graft to the rabbit knee cartilage of defect
Biocompatibility bone graft is implanted into and repairs rabbit knee cartilage defect, after 6 months, observe the work of rabbit knee Dynamic behavior, the cartilaginous tissue for taking reparation position carry out histological observation, the biocompatibility bone graft pair of overall merit each group Application effect after the skin grafing and mending of the rabbit knee cartilage of defect.This index is used as the replacement graft of cartilaginous tissue Most critical evaluation index.
Experimental result:The biocompatibility bone graft experimental result of above each group is shown in Table 2.
As seen from the data in Table 2, each experimental group is in porosity, pore size, water absorption, modulus of compressibility and stretch moduluses etc. Differ in performance indications not substantially, property indices are excellent, and external contact compatibility be good in vivo, the crawler behavior of rabbit knee and The indexs such as Histological evaluation are good, demonstrate experimental group for the rabbit knee cartilage of defect has good skin grafing and mending effect.
In matched group, the index of the modulus of compressibility of control 2 and stretch moduluses is very poor, the performance indications and reality of remaining matched group Test group be close to, but matched group for rabbit knee cartilage defect repair effect poor, transplanting posterior joint occur deform.Even control Group 4, from the cartilage Acellularized valve composition of higher mammal mice, substitutes the cartilage Acellularized valve composition of Amphibian, but For rabbit knee cartilage defect repair effect is still poor, and need can be only achieved longer repair time to be close to experimental group Repairing effect.
From the foregoing, it will be observed that experimental group works well for the skin grafing and mending of the rabbit knee cartilage to defect, can be used as bone The replacement graft of tissue.And the matched group for lacking the biocompatibility bone graft key component of the present invention cannot function as joint The graft substitute application of cartilage defect, even if the cartilage Acellularized valve composition for replacing higher mammal mice replaces the present invention's The cartilage Acellularized valve composition of Amphibian, can not obtain good Bone Defect Repari effect.
The results of property and application effect of each experimental group of 2 biocompatibility bone graft of table
Above-mentioned detailed description is illustrating for the possible embodiments for invention, and the embodiment is simultaneously not used to limit this Bright the scope of the claims, all equivalence enforcement or changes without departing from the present invention, should be contained in the scope of the claims of the present invention.
In addition, those skilled in the art can also the claims in the present invention scope of disclosure and spirit in do other forms with Various modifications, interpolation and replacement in details.Certainly, these are made according to present invention spirit various modifications, interpolation and replacement Deng change, should all be included within scope of the present invention.

Claims (9)

1. a kind of biocompatibility bone graft and preparation method thereof, it is characterised in that:Described biocompatibility bone graft Key component include fibroin albumen, polyvinyl alcohol, calcium salt, the cartilage Acellularized valve composition of Amphibian and osteogenic induction because Son, can pass through to change component proportion, control the mechanical strength and degradation speed of bone graft.
2. preparation method according to claim 1, it is characterised in that:Fibroin egg in described biocompatibility bone graft White weight/mass percentage composition is 10%-30%, the weight/mass percentage composition of polyvinyl alcohol is 1%-5%, the quality percentage of calcium salt contains The weight/mass percentage composition for measuring the cartilage Acellularized valve composition for 20%-50%, Amphibian is 20%-50%, osteogenic induction The weight/mass percentage composition of the factor is 0.1%-10%.
3. biocompatibility bone graft according to claim 1, is characterized in that:Described calcium salt includes hydroxy-apatite Stone, calcium sulfate, calcium citrate, calcium phosphate, halobiontic bone shell and its extract.
4. biocompatibility bone graft according to claim 3, is characterized in that:Can contain in described calcium salt structure The water of crystallization of varying number.
5. biocompatibility bone graft according to claim 1, is characterized in that:Described Osteoinductive Factor includes sulfur Aching and limp ossein, hyaluronic acid, collagen, promote bone growth bioactie agent one or more.
6. according to any one of Claims 1 to 5 biocompatibility bone graft preparation method, it is characterized in that:Will be described Amphibian cartilage Acellularized valve crush, with calcium salt, fibroin albumen and Osteoinductive Factor mix, add polyvinyl alcohol Ethanol solution, mixes, and forms uniform semisolid, is placed in drying and moulding in metal die, forms the three-dimensional tubulose containing hollow duct Bone graft, gamma-radiation irradiation sterilization.
7. a kind of preparation method of biocompatibility bone graft according to any one of Claims 1 to 5, is characterized in that:Will The cartilage Acellularized valve of described Amphibian is crushed, and is mixed with calcium salt and fibroin albumen, is added polyvinyl alcohol ethanol solution, Mix, form uniform semisolid, be placed in drying and moulding in metal die, form the three-dimensional tubulose bone graft containing hollow duct, Inner chamber and the surface that the solution containing Osteoinductive Factor is distributed in by immersion or coating method for three-dimensional tubulose bone graft, The Osteoinductive Factor coating that sticks beneficial to chondrocyte and regenerate, gamma-radiation irradiation sterilization is formed with after drying.
8. the preparation method of the biocompatibility bone graft according to claim 6~7, is characterized in that:Described biology For pharmacy conventional pH buffer, antioxidant, surfactant are further added in the preparation process of compatibility bone graft.
9. the biocompatibility bone graft according to claim 1-7, is characterized in that:Described biocompatibility bone collection Thing is used for the replacement graft of osseous tissue defect.
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