CN103055352A - Calcium phosphate/collagen composite biologic ceramic material and preparation method thereof - Google Patents
Calcium phosphate/collagen composite biologic ceramic material and preparation method thereof Download PDFInfo
- Publication number
- CN103055352A CN103055352A CN2013100221048A CN201310022104A CN103055352A CN 103055352 A CN103055352 A CN 103055352A CN 2013100221048 A CN2013100221048 A CN 2013100221048A CN 201310022104 A CN201310022104 A CN 201310022104A CN 103055352 A CN103055352 A CN 103055352A
- Authority
- CN
- China
- Prior art keywords
- calcium phosphate
- ceramic
- collagen
- preparation
- composite
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Abstract
The invention relates to a CaP (Calcium Phosphate)/collagen composite biologic ceramic material and a preparation method thereof. The composite biologic ceramic is prepared by adopting a porous calcium phosphate ceramic as the substrate and I-type collage as the toughening reinforcing phase in a vacuum negative pressure pouring and crosslinking mode. The process is as follows: firstly, preparing the first type through porous calcium phosphate ceramic, wherein the porosity is 60-95%; dipping the porous calcium phosphate ceramic into a collagen solution of which the concentration is 5-20mg/ml; and vacuuming to 0-10Pa at normal temperature and pouring, keeping the pressure for 1-3 hours and carrying out ultrasonic oscillation. The vacuum negative pressure pouring process can be repeated according to demands. The calcium phosphate ceramic poured with the collagen is frozen and dried to prepare the composite biologic ceramic after being subjected to crosslinking. The prepared biologic ceramic has good biocompatibility and biological activity, and at the same time has a mechanical strength better than that of a pure calcium phosphate ceramic material, so that the biologic ceramic can be used as artificial bones and bone tissue engineering bracket materials, and has wide clinical application prospects in orthopedics.
Description
Technical field
The present invention relates to compound bioceramic material of a kind of porous calcium phosphate ceramic and collagen protein and preparation method thereof, belong to field of biomedical materials.
Background technology
Calcium phosphate biological ceramic material (Calcium Phosphate Bioceramics, CaP) because it has the inorganic constituents similar with body bone tissue, and has both multiple good biological characteristics and is widely used as bone renovating material.Common series of calcium phosphate bioceramic material comprises hydroxyapatite (Hydroxyapatite, HA), β phase tricalcium phosphate (beta-Tricalcium phosphate, β-TCP) and their complex biophasic calcium phosphate ceramic (Biphasic calcium phosphate, BCP) etc.Existing studies confirm that, porous calcium phosphate is that bioceramic possesses the required biological characteristics of numerous bone renovating materials, such as biocompatibility, bone conduction and bone inducibility, biodegradable absorption etc.Their forms with granule or small blocks in clinical are widely used in the damaged reparation filling of non-bearing position bone; yet because of its at the application requirements that can not satisfy heavy burden bone defect repair aspect the mechanical property, so the reparation that this type of bioceramic material is used for the bearing position osseous tissue remains a difficult point that needs to be resolved hurrily.On the basis that guarantees the good biology performance of calcium phosphate biological ceramic material, further improve its mechanical property, in conjunction with organism internal skeleton structural stress environment, the new bone formation of rapid induction and final reconstruction defect osseous tissue are to be expected to solve the desirable approach that bearing position bone defect repair is rebuild.
Desirable load bone reparing biological material should have both good biology performance and mechanical property simultaneously.Biology performance wishes that mainly it has good biocompatibility, bone conductibility, osteoinductive and osteogenesis ability.Mechanical property comprises resistance to compression, bending strength, and a plurality of aggregative indicatores such as elastic modelling quantity can approach to greatest extent or be complementary with the mechanical property of natural bone.Existing research thinks, the composition of material, interface and micropore structure have decisive action to the bone inducibility of calcium phosphate ceramic.Clinical research confirmation, although most of calcium phosphate ceramic shows good biological characteristics, can be well and human body hard tissue and soft tissue bio-compatible, but result of study shows simultaneously dense calcium phosphate ceramics and can not effectively induce the formation of new bone tissue, and the calcium phosphate ceramic that only has loose structure just possesses bone and induces generative capacity.In its microscopic void, can adsorb/required related gene and the albumen of the new osteogenesis of enrichment after in the porous calcium phosphate ceramic implantable bioartificial body, promote simultaneously the generation of new capillary vessel tissue, and early stage vascularization can provide the required nutrient condition of skeletonization and carry metabolite, be beneficial to osteoblastic differentiation and propagation, and then induce the generation of new bone tissue.Therefore, microcellular structure is most important to osteoinductive and the osteogenesis ability of series of calcium phosphate bioceramic material.Based on this, existing Patents technology (method for preparing porous structure ceramic artificial bone, the patent No.: CN1903384; The porous bio-ceramic of controllable microstructure, its preparation method and application, the patent No.: CN 1268583C) preparation and the optimization of calcium phosphate porous structure are reported.Obviously, because the intervention of pore structure and the fragility characteristics of calcium phosphate ceramic self will certainly reduce the mechanical property of materials, thereby restrict this type of bioceramic material is used as the reparation of load osseous tissue.Therefore the technology report is arranged by the mechanical property of Material cladding technology with the raising ceramic material.For example patent CN1935270A has reported a kind of take hydroxyapatite as matrix, diopside and aluminium oxide are composite bioceramic material and the technology of preparing thereof of toughened and reinforced body, and the composite boilogical ceramic of this technology preparation has than mechanical properties such as the better fracture toughness of pure HA, bending strengths.
The main component of natural bone comprises inorganic calcium phosphate and organic collagen protein, and wherein inorganic calcium phosphate contains the biological phosphorus lime stone of 60～75 mass percents of having an appointment take the apatite of biomineralization as main (Biological apatite) in the bone.Collagen protein (Collagen) is a kind of natural polymer, and it is the main organic principle of human body skin and bone, is the rich in protein of content in the bone matrix.Collagen protein has good biocompatibility and low immunity, is suitable as the substrate that new osteocyte attaches growth, is a kind of ideal material for bone tissue restoration.Nearest existing research is devoted to develop the preparation collagen-base or is used as the reparation of osseous tissue as the biomaterial that adds phase with it.A kind of mineralized collagen is disclosed among the foreign patent WO 93/12736 as the method for bone tissue restoration.But it is only applicable to non-bearing position osseous tissue repair in trauma.
Based on characteristic and the shortcoming of series of calcium phosphate bioceramic, the object of the present invention is to provide a kind of method for preparing calcium phosphate and collagen protein composite biological material.The composite of the present invention's preparation can improve the mechanical property of bioceramic, and the composition of the further analog bone substrate of energy, with this type of pottery as the bone tissue restoration timbering material, the function that will have the regeneration of good mechanical property and induced tissue is expected to promote the reconstruction of bearing position osseous tissue to use.
Summary of the invention
The object of the present invention is to provide a kind of calcium phosphate and collagen protein composite biological material.
The present invention is achieved through the following technical solutions:
A kind of calcium phosphate/collagen albumen composite bioceramic material is composited by porous calcium phosphate ceramic and collagen protein.
As optimal way, this composite boilogical ceramic is take porous calcium phosphate ceramic as matrix, and collagen protein is toughened and reinforced phase, and the mass percent of each raw material (Wt%) is: calcium phosphate ceramic 80%～98%, collagen protein 2～20%.
As optimal way, described porous calcium phosphate ceramic pore structure characteristic is that ceramic overall porosity is 60%～95%, and macropore diameter is 100～500 microns, has micropore mutually to connect between the macropore, and the macropore inwall is covered with the capillary micropore.
As optimal way, described porous calcium phosphate ceramic adopts hydrogen peroxide foaming or microsphere occupy-place method or slip casting method preparation, and the ceramic material composition is: hydroxyapatite, β phase tricalcium phosphate or biophasic calcium phosphate ceramic.
As optimal way, described collagen protein is the I-collagen type.
As optimal way, described collagen protein forms three-dimensional collagen fabric network structure in ceramic hole.
Another object of the present invention is to provide a kind of preparation method of above-mentioned calcium phosphate/collagen albumen composite bioceramic material, its operating procedure comprises:
(a) the preparation IPN connects porous calcium phosphate ceramic: prepare ceramic porous structure idiosome, then through sintering porcelain into.
(b) perfusion: the preparation collagen solution, the porous ceramics with preparation in the collagen solution submergence step (a) carries out priming by vacuum under the room temperature, then, product is carried out ultrasonic wave concussion stir.
(c) crosslinked: the calcium phosphate ceramic that will pour into collagen protein carries out crosslinked through physics or chemical method, at last product is carried out lyophilization.
As optimal way, idiosome described in the step (a) adopts hydrogen peroxide foaming or microsphere occupy-place method or slip casting method preparation, and the temperature of described sintering is 1000～1200 ℃; Collagen solution concentration described in the step (b) is 5～20 mg/ml, described priming by vacuum process is for being evacuated to 0～10 Pa, pressurize 1～3 hour, described priming by vacuum and sonic oscillation process can repeat as required, and the time that described concussion is stirred is 5～20 minutes; Cross-linking method described in the step (c) is crosslinked (the J Mech Behav Biomed of genipin, 2012,15:176-189.), UV-crosslinked (J Biomed Mater Res. 1995,29 (11): 1373-1379), cross-linking radiation (Radiat Res. 1964,22 (4): 606-621), glutaraldehyde cross-linking (J Mater Sci-Mater M, 1995, a kind of 6:460-472), described cryodesiccated temperature is-60 ℃～-20 ℃, and the time is 24～48 hours.
The present invention also provides a kind of purposes of described calcium phosphate/collagen albumen composite bioceramic material: used as human body hard tissue damaged reparation or scaffold material of bone tissue engineering.Particularly use it for bearing position osseous tissue repair in trauma.
Beneficial effect of the present invention:
1, the composition of Simulation of Composite natural bone substrate of the present invention had both significantly improved the mechanical property of bioceramic, had promoted again its bone tissue restoration regeneration function.In biomedical sector, have huge application prospect, in particular for the damaged repair and reconstruction of sclerous tissues, as repairing the filling bracket material, induce rapidly the generation of new bone tissue in the os osseum defect, strengthen bone connection and healing function.
2, described composite material by adopting has sintered the porous calcium phosphate ceramic of porcelain into as matrix, there is micropore mutually to connect between its macropore, the macropore inwall is covered with the capillary micropore, this structure makes composite have good osteoinductive and osteogenesis ability on the one hand, be conducive on the other hand hold more collagen protein, make it enter material internal, and form tridimensional network.
3, collagen protein is cross-linked with each other in ceramic hole and forms three-dimensional collagen fabric network structure in the described composite, this structure is conducive to improve the mechanical property of material on the one hand, promote toughened and reinforced effect, loose structure with ceramic matrix material forms sealed on the other hand, make both combinations more firm, material is more stable, also is conducive to simultaneously cell tactophily on it.
4, adopt the I-collagen type.Collagen protein is a kind of GL-PP, contains a small amount of half lactic acid and glucose, is the main component of extracellular matrix, also is one of most important composition in the human body simultaneously.It extensively is present among the tissues such as skin, skeleton, muscle, cartilage, joint of human body.Wherein mainly have the I-collagen type in human body os osseum tissue, it plays the multi-efficiencies such as support, protection and reparation.Mainly by fibroblast or synthetic with the similar cell in its source such as osteoblast, it induces osteanagenesis reconstruction aspect that important biological effect is arranged promoting osteocyte propagation, differentiation to the I-collagen type.
5, in the composite manufacture method of the present invention, collagen protein by negative pressure of vacuum perfusion certain viscosity, realize the compound of porous ceramics and collagen protein, whole technique is the physics recombination process, participate in without chemical reaction and organic solvent, avoided preparation technology to admix poisonous and harmful substances at home and abroad to the pollution of bioceramic.By ultrasonic wave concussion and repeat to be perfused with to be beneficial to and improve the collagen protein loading, it is adsorbed equably be filled among the ceramic hole.Cross-linking process is conducive to collagen protein and forms the netted structure of three-dimensional fiber.
Description of drawings
Fig. 1 is preparation technology's flow chart of the present invention;
Fig. 2 is the portioned product figure that the present invention prepares, and totally 3 groups, every group of two samples are respectively tricalcium phosphate/collagen protein composite ceramics, biphasic calcium phosphate/collagen protein composite ceramics and hydroxyapatite/collagen albumen composite ceramics from left to right;
Fig. 3 is the SEM shape appearance figure of calcium phosphate/collagen albumen composite ceramic material among the embodiment, wherein the SEM shape appearance figure of (a) little pure ha porous ceramics; (b) be the SEM shape appearance figure of the biological material of embodiment 1 hydroxyapatite/collagen albumen composite ceramics; (c) be the SEM shape appearance figure of the biological material of embodiment 2 tricalcium phosphates/collagen protein composite ceramics; (d) be the SEM shape appearance figure of the biological material of embodiment 3 biphasic calcium phosphates/collagen protein composite ceramics;
Fig. 4 is the Mechanics Performance Testing figure of calcium phosphate/collagen albumen composite bioceramic material;
Fig. 5 is biphasic calcium phosphate/collagen protein composite ceramic material Marrow Mesenchymal Stem Cells In Vitro (MSCs) laser co-focusing displaing micro picture, and wherein (a) is cell seeding 1 day; (b) be cell seeding 3 days; (c) be cell seeding 7 days; (d) be cell seeding 21 days.
The specific embodiment
Below in conjunction with accompanying drawing technique of the present invention is described in further detail.
Preparation technology's flow process of the present invention as shown in Figure 1.Raw-material preparation is divided into two aspects, the preparation of the calcium phosphate ceramic body of the suitable hole of the first, and it two is that the preparation of type i collagen protein solution is prepared.The calcium phosphate ceramic that the present invention was suitable for mainly comprises following three classes: hydroxyapatite (Hydroxyapatite, HA), tricalcium phosphate (beta-Tricalcium phosphate, β-TCP), and biophasic calcium phosphate ceramic (Biphasic calcium phosphate, BCP), the making of the porous ceramic bodies that relates to can be via hydrogen peroxide foaming (Chinese patent: CN1903384), microgranule occupy-place method (Chinese patent: CN 1268583C), slip casting method (United States Patent (USP): No.3090094) or additive method prepare the porous ceramics idiosome, the porous calcium phosphate ceramic that then forms through calcining.The pottery that the embodiment of the invention is used prepares idiosome by the hydrogen peroxide foaming, and ceramic overall porosity is 60%～95%, and macropore diameter is 100～500 microns, has micropore mutually to connect between the macropore.The collagen protein that the present invention is suitable for is all kinds collagen protein, and the embodiment of the invention is used through sterilization, purification, gone the present invention that demonstrates of the first type calf cow leather collagen of immune terminal amino acid.Employed collagen content is 5～20% mass percents in the complex ceramic body, prepares the use collagen solution by the concentration of 5～20 mg/ml.
The following several most preferred embodiment of the present invention of classifying as it should be understood that these embodiment only are used for the purpose of illustration, never limit protection scope of the present invention.
Take hydroxyapatite powder as raw material, the cuboid porous calcium phosphate ceramic product of preparation 5 * 5 * 20 mm.The holes of products gap structure requires: whole porosity 85% ± 5%, macropore diameter are that 400 ± 50 μ m, IPN perforation micropore size are 80 ± 20 μ m.Concrete steps are as follows:
1) will be through the hydroxyapatite powder that Wet Method Reaction makes standard model sieve, filtering out diameter is the hydroxyapatite dry powder of 80～160 μ m, adopts subsequently the hydrogen peroxide foaming to prepare the porous ceramics idiosome, low temperature＜100 ℃ oven dry;
2) ceramic idiosome is put into the Muffle furnace sintering, be warming up to 1100 ℃ from room temperature with the speed of 5 ℃/min and continue 2 hours sintering, then furnace cooling.To obtain the cuboid that Porous Hydroxyapatite Ceramic cuts into 5 * 5 * 20 mm subsequently;
3) will be through sterilization, purification, remove the I-type calf cow leather collagen of immune terminal amino acid, with the deionized water dilution and by the concentration preparation collagen solution of 5 mg/ml;
4) the collagen solution submergence porous ceramics to prepare, room temperature be evacuated to＜and 10 Pa pour into, and pressurize 3 hours was stirred 10 minutes through ultrasonic wave concussion again, repeated evacuation negative pressure filling process once.
The pottery that 5) will pour into collagen protein crosslinked 48 hours with the genipin of 10 mg/ml is again with-20 ℃ of temperature lyophilizations 24 hours.
The scanning electron microscope picture of the hydroxyapatite/collagen albumen composite bioceramic material of gained as shown in Figure 3, recording its maximum compressive strength through universal testing machine is that 8.7 MPa(method of testings are referring to GB/T 1964-1996), than 3.1 times of pure ha porous bio-ceramic material lift.
Embodiment 2:
Take porous beta-calcium phosphate ceramics as matrix, preparation tricalcium phosphate/collagen protein (TCP/Collagen) composite ceramic material.Ceramic integral porosity 85% ± 5%, macropore diameter are that 400 ± 50 μ m, IPN perforation micropore size are 80 ± 20 μ m, and all the other product preparation process and step are identical with embodiment 1.The scanning electron microscope picture of the tricalcium phosphate of gained/collagen protein composite bioceramic material as shown in Figure 3, recording its maximum compressive strength through universal testing machine is 5.4 MPa, mechanical property than the porous beta before the composite collagen-calcium phosphate ceramics material promotes approximately 2.9 times, than low 3.8 MPa of comprcssive strength of hydroxyapatite/collagen albumen (HA/Collagen) composite ceramics among the embodiment 1, this is because the mechanical property of pure phosphoric acid DFP pottery own is just poor than the pure ha pottery.
Take the porous biophasic calcium phosphate ceramic as matrix, preparation biphasic calcium phosphate/collagen protein (BCP/Collagen) composite ceramic material.Ceramic integral porosity 85% ± 5%, macropore diameter are that 400 ± 50 μ m, IPN perforation micropore size are 80 ± 20 μ m, and all the other product preparation process and step are identical with embodiment 1.The scanning electron microscope picture of the biphasic calcium phosphate of gained/collagen protein composite bioceramic material as shown in Figure 3, recording its maximum compressive strength through universal testing machine is 6.7 MPa, mechanical property than the porous biophasic calcium phosphate ceramic material before the composite collagen promotes approximately 3.0 times, comprcssive strength than hydroxyapatite/collagen albumen (HA/Collagen) composite ceramics among the embodiment 1 is low, but the comprcssive strength than tricalcium phosphate/collagen protein (TCP/Collagen) composite ceramics among the embodiment 2 is high, this be because the mechanical property of pure phosphoric acid calcium pottery under the same conditions, its mechanical strength ordering is: HA＞BCP＞TCP.
Embodiment 4
Other condition and technique are with embodiment 1, it is compound that difference is to adopt the hydroxylapatite ceramic of different pore structures to be that matrix carries out the collagen protein perfusion, and its ceramic porosity 95% ± 5%, macropore diameter are that to connect micropore size be 100 ± 20 μ m for 500 ± 100 μ m, IPN.It is 8.2 MPa that the hydroxyapatite/collagen albumen composite bioceramic material of gained records maximum its comprcssive strength through universal testing machine, mechanical property than the hydroxylapatite ceramic material before the composite collagen promotes approximately 2.9 times, but than low 0.5 MPa of comprcssive strength of the hydroxyapatite/collagen albumen composite ceramics of gained among the embodiment 1, the porous skeleton structure of this presentation of results calcium phosphate ceramic has important function aspect the mechanical property of composite.Although the increase in ceramic integral porosity and aperture, promoted the increase of collagen content in the composite, when increasing because of its porosity and aperture, sacrificed the mechanical strength of material itself, thereby the mechanical property of the material after finally compound descends to some extent than embodiment 1.
Embodiment 5
Other condition and technique is with embodiment 1, and it is compound that difference is to adopt the collagen protein of variable concentrations to pour into, and its collagen concentration is 20 mg/ml, and through genipin crosslinked 72 hours.The hydroxyapatite/collagen albumen composite bioceramic material of gained, recording its maximum compressive strength through universal testing machine is 9.1 MPa, comparatively the mechanical property of composite collagen pre-ceramic material promotes approximately 3.3 times, and compound more collagen protein is conducive to the lifting of the final mechanical property of material in this presentation of results calcium phosphate ceramic pore structure.
With after the biphasic calcium phosphate of embodiment 3 preparation/collagen protein composite ceramic material sterilization and mesenchymal stem cells MSCs (MSCs) cultivated altogether for 3 weeks external, respectively when cultivating 1 day, 3 days, 7 days and 21 days, adopt diacetic acid fluorescein/propidium iodide (FDA/PI) that cell is dyeed, then adopt confocal laser scanning microscope and take pictures, the result shows (as shown in Figure 5), cell is attached at pottery/collagen inwall growth, in this material differentiation, propagation obviously.Material has induces osteanagenesis and speeds the function that the bone defect repairing is rebuild.
With method of the present invention, the calcium phosphate/collagen albumen composite bioceramic material of preparing has greatly promoted the mechanical property of pure phosphoric acid calcium porous ceramic film material.Collagen protein after crosslinked, in ceramic hole, be three-dimensional collagen fabric network structure, give the enough mechanical strengths of material and toughness, by the composition of composite collagen analog bone substrate, make material have preferably biocompatibility and biological activity simultaneously.
The above only is the preferred embodiments of the present invention, only is illustrative for the purpose of the present invention, and nonrestrictive; Those of ordinary skills understand, and can carry out many changes to it in the spirit and scope that claim of the present invention limits, revise, even the equivalence change, but all will fall into protection scope of the present invention.
Claims (10)
1. a calcium phosphate/collagen albumen composite bioceramic material is characterized in that it is to be composited by porous calcium phosphate ceramic and collagen protein.
2. composite bioceramic material according to claim 1 is characterized in that, the mass percent of each raw material (wt%) is: calcium phosphate ceramic 80%～98%, collagen protein 2～20%.
3. composite bioceramic material according to claim 1, it is characterized in that, described porous calcium phosphate ceramic pore structure characteristic is that ceramic overall porosity is 60%～95%, and macropore diameter is 100～500 microns, have micropore mutually to connect between the macropore, the macropore inwall is covered with the capillary micropore.
4. composite bioceramic material according to claim 1, it is characterized in that, described porous calcium phosphate ceramic adopts hydrogen peroxide foaming or microsphere occupy-place method or slip casting method preparation, and the ceramic material composition is: hydroxyapatite, β phase tricalcium phosphate or biophasic calcium phosphate ceramic.
5. composite bioceramic material according to claim 1 is characterized in that, described collagen protein forms three-dimensional collagen fabric network structure in ceramic hole.
6. composite bioceramic material according to claim 1 is characterized in that, described collagen protein is the I-collagen type.
7. the preparation method of a calcium phosphate/collagen albumen composite bioceramic material as claimed in claim 1 is characterized in that, its operating procedure comprises:
(a) the preparation IPN connects porous calcium phosphate ceramic: prepare ceramic porous structure idiosome, then through sintering porcelain into.
(b) perfusion: the preparation collagen solution, the porous ceramics with preparation in the collagen solution submergence step (a) carries out priming by vacuum under the room temperature, then, product is carried out ultrasonic wave concussion stir.
(c) crosslinked: the calcium phosphate ceramic that will pour into collagen protein carries out crosslinked through physics or chemical method, at last product is carried out lyophilization.
8. the preparation method of calcium phosphate/collagen albumen composite bioceramic material according to claim 7, it is characterized in that, idiosome described in the step (a) adopts hydrogen peroxide foaming or microsphere occupy-place method or slip casting method preparation, and the temperature of described sintering is 1000～1200 ℃; Collagen solution concentration described in the step (b) is 5～20 mg/ml, described priming by vacuum process is for being evacuated to 0～10 Pa, pressurize 1～3 hour, described priming by vacuum and sonic oscillation process are carried out once at least, and the time that described concussion is stirred is 5～20 minutes; Cross-linking method described in the step (c) is that genipin is crosslinked, UV-crosslinked, a kind of in the cross-linking radiation, glutaraldehyde cross-linking, and described cryodesiccated temperature is-60 ℃～-20 ℃, and the time is 24～48 hours.
9. the purposes of a calcium phosphate/collagen albumen composite bioceramic material as claimed in claim 1 is characterized in that, used as human body hard tissue damaged reparation or scaffold material of bone tissue engineering.
10. the purposes of calcium phosphate/collagen albumen composite bioceramic material according to claim 9 is characterized in that, uses it for bearing position osseous tissue repair in trauma.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310022104.8A CN103055352B (en) | 2013-01-22 | 2013-01-22 | Calcium phosphate/collagen composite biologic ceramic material and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310022104.8A CN103055352B (en) | 2013-01-22 | 2013-01-22 | Calcium phosphate/collagen composite biologic ceramic material and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103055352A true CN103055352A (en) | 2013-04-24 |
| CN103055352B CN103055352B (en) | 2014-12-10 |
Family
ID=48098440
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310022104.8A Expired - Fee Related CN103055352B (en) | 2013-01-22 | 2013-01-22 | Calcium phosphate/collagen composite biologic ceramic material and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103055352B (en) |
Cited By (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103341206A (en) * | 2013-06-09 | 2013-10-09 | 四川大学 | Calcium phosphate/collagen/bone-like apatite three-level bionic bone tissue engineering scaffold and preparation method thereof |
| CN103638556A (en) * | 2013-12-03 | 2014-03-19 | 四川大学 | Surface nano-scale modified calcium phosphate bioactive ceramic as well as preparation method and application thereof |
| CN103800944A (en) * | 2014-02-24 | 2014-05-21 | 李陵江 | Bone-grafting filling material and preparation method thereof |
| CN104800896A (en) * | 2015-04-20 | 2015-07-29 | 东华大学 | Human body-absorbable and enhancement-type bone fixation structure material 3D printed with FDM (fused deposition modeling) technology and preparation method thereof |
| CN105343935A (en) * | 2014-12-15 | 2016-02-24 | 四川大学 | Calcium phosphate whisker frame and porous composite scaffold and their preparation methods |
| CN105561385A (en) * | 2016-01-07 | 2016-05-11 | 巴斯特医药科技（常州）有限公司 | Manufacturing method of bone filling material with biological ceramic surface activated layer |
| WO2017097104A1 (en) * | 2015-12-07 | 2017-06-15 | 廖化 | Bone repair reusable composite material based on acellular biological tissue matrix material and preparation method therefor |
| CN106866128A (en) * | 2017-02-27 | 2017-06-20 | 合肥中科富华新材料有限公司 | A kind of bioceramic material and preparation method |
| CN107308503A (en) * | 2017-06-16 | 2017-11-03 | 无锡贝迪生物工程股份有限公司 | A kind of plasticity artificial bone and preparation method thereof |
| CN107711417A (en) * | 2017-11-26 | 2018-02-23 | 来安县杭姑娘生态农业有限公司 | A kind of cheap cucumber soilless culture substrate of cost |
| CN107889722A (en) * | 2017-11-26 | 2018-04-10 | 来安县杭姑娘生态农业有限公司 | A kind of soilless culture substrate for improving cucumber yield |
| CN107950350A (en) * | 2017-11-26 | 2018-04-24 | 来安县杭姑娘生态农业有限公司 | A kind of cucumber soilless culture substrate full of nutrition |
| CN107980543A (en) * | 2017-11-26 | 2018-05-04 | 来安县杭姑娘生态农业有限公司 | A kind of special soilless culture substrate of lightweight cucumber |
| CN108066817A (en) * | 2017-12-06 | 2018-05-25 | 常州琨瑶纺织品有限公司 | A kind of nano bone repair material and preparation method thereof |
| JP2018094394A (en) * | 2016-12-12 | 2018-06-21 | オリンパステルモバイオマテリアル株式会社 | Bone prosthetic material and method for producing bone prosthetic material |
| CN110038158A (en) * | 2019-05-27 | 2019-07-23 | 中国人民解放军第四军医大学 | The formula and preparation method thereof of photocuring 3D printing Haversian system artificial bone scaffold |
| CN110408087A (en) * | 2019-08-05 | 2019-11-05 | 中国科学技术大学 | A kind of bionic ceramic sill and preparation method thereof based on the optimization of nanoscale overstrain |
| CN111346262A (en) * | 2020-03-17 | 2020-06-30 | 四川大学 | Injectable calcium-phosphorus ceramic for promoting healing of tendon and bone and preparation method and application thereof |
| CN112043873A (en) * | 2020-09-16 | 2020-12-08 | 浙江甬誉生物科技有限公司 | Organic polymer bridging-containing bio-inorganic composite structure material and preparation method and application thereof |
| CN112745142A (en) * | 2021-03-04 | 2021-05-04 | 四川大学 | Graphene/calcium phosphate ceramic composite bracket with antibacterial function and preparation method thereof |
| CN113041398A (en) * | 2021-03-16 | 2021-06-29 | 上海大学绍兴研究院 | High-entropy ceramic composite collagen material, preparation method and application thereof, and high-entropy ceramic composite collagen artificial bone |
| US11357891B2 (en) * | 2019-06-14 | 2022-06-14 | Geistlich Pharma Ag | Collagen matrix or granulate blend of bone substitute material |
| CN114712557A (en) * | 2022-04-02 | 2022-07-08 | 中山大学附属口腔医院 | Hydrogel reinforced biological bone calcium apatite scaffold and manufacturing method thereof |
| CN115177787A (en) * | 2022-07-29 | 2022-10-14 | 奥精医疗科技股份有限公司 | 3D printing composite bone repair material and preparation method and application thereof |
| CN115252891A (en) * | 2022-08-26 | 2022-11-01 | 四川大学 | Preparation method of calcium phosphate ceramic for drug loading and drug loading method |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3090094A (en) * | 1961-02-21 | 1963-05-21 | Gen Motors Corp | Method of making porous ceramic articles |
| EP0361896A2 (en) * | 1988-09-29 | 1990-04-04 | Collagen Corporation | Method for improving implant fixation |
| CN1647826A (en) * | 2005-02-01 | 2005-08-03 | 翁文剑 | Medical beta phase tricalcium phosphate/collagen cmposite material and its preparing method |
| CN101530634A (en) * | 2009-04-21 | 2009-09-16 | 昆明医学院第一附属医院 | Bionic dual-phase ceramic-like biologically active bone and manufacturing method thereof |
| US20110182965A1 (en) * | 2010-01-26 | 2011-07-28 | Warsaw Orthopedic, Inc. | Highly compression resistant matrix with porous skeleton |
-
2013
- 2013-01-22 CN CN201310022104.8A patent/CN103055352B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3090094A (en) * | 1961-02-21 | 1963-05-21 | Gen Motors Corp | Method of making porous ceramic articles |
| EP0361896A2 (en) * | 1988-09-29 | 1990-04-04 | Collagen Corporation | Method for improving implant fixation |
| CN1647826A (en) * | 2005-02-01 | 2005-08-03 | 翁文剑 | Medical beta phase tricalcium phosphate/collagen cmposite material and its preparing method |
| CN101530634A (en) * | 2009-04-21 | 2009-09-16 | 昆明医学院第一附属医院 | Bionic dual-phase ceramic-like biologically active bone and manufacturing method thereof |
| US20110182965A1 (en) * | 2010-01-26 | 2011-07-28 | Warsaw Orthopedic, Inc. | Highly compression resistant matrix with porous skeleton |
Cited By (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103341206A (en) * | 2013-06-09 | 2013-10-09 | 四川大学 | Calcium phosphate/collagen/bone-like apatite three-level bionic bone tissue engineering scaffold and preparation method thereof |
| CN103341206B (en) * | 2013-06-09 | 2014-11-19 | 四川大学 | Calcium phosphate/collagen/bone-like apatite three-level bionic bone tissue engineering scaffold and preparation method thereof |
| CN103638556A (en) * | 2013-12-03 | 2014-03-19 | 四川大学 | Surface nano-scale modified calcium phosphate bioactive ceramic as well as preparation method and application thereof |
| CN103800944A (en) * | 2014-02-24 | 2014-05-21 | 李陵江 | Bone-grafting filling material and preparation method thereof |
| CN103800944B (en) * | 2014-02-24 | 2015-11-25 | 李陵江 | Bone-grafting filling material and preparation method thereof |
| CN105343935A (en) * | 2014-12-15 | 2016-02-24 | 四川大学 | Calcium phosphate whisker frame and porous composite scaffold and their preparation methods |
| CN104800896A (en) * | 2015-04-20 | 2015-07-29 | 东华大学 | Human body-absorbable and enhancement-type bone fixation structure material 3D printed with FDM (fused deposition modeling) technology and preparation method thereof |
| CN104800896B (en) * | 2015-04-20 | 2017-12-08 | 东华大学 | A kind of human body of FDM technology 3D printing can absorb enhanced bone fixation structural material and preparation method thereof |
| WO2017097104A1 (en) * | 2015-12-07 | 2017-06-15 | 廖化 | Bone repair reusable composite material based on acellular biological tissue matrix material and preparation method therefor |
| US10821207B2 (en) | 2015-12-07 | 2020-11-03 | Hangzhou Huamai Medical Devices Co., Ltd. | Composite materials for bone repair based on decellularized biological tissue matrix material and the preparation method thereof |
| JP2018529499A (en) * | 2015-12-07 | 2018-10-11 | ハンチョウ フアマイ メディカル デバイシズ カンパニー リミテッド | Composite material for bone repair based on decellularized biological tissue matrix material and method for preparing it |
| CN105561385A (en) * | 2016-01-07 | 2016-05-11 | 巴斯特医药科技（常州）有限公司 | Manufacturing method of bone filling material with biological ceramic surface activated layer |
| JP7158847B2 (en) | 2016-12-12 | 2022-10-24 | オリンパステルモバイオマテリアル株式会社 | Bone substitute material and method for producing bone substitute material |
| JP7177588B2 (en) | 2016-12-12 | 2022-11-24 | オリンパステルモバイオマテリアル株式会社 | Bone substitute material and method for producing bone substitute material |
| JP2018094394A (en) * | 2016-12-12 | 2018-06-21 | オリンパステルモバイオマテリアル株式会社 | Bone prosthetic material and method for producing bone prosthetic material |
| CN106866128A (en) * | 2017-02-27 | 2017-06-20 | 合肥中科富华新材料有限公司 | A kind of bioceramic material and preparation method |
| CN107308503A (en) * | 2017-06-16 | 2017-11-03 | 无锡贝迪生物工程股份有限公司 | A kind of plasticity artificial bone and preparation method thereof |
| CN107980543A (en) * | 2017-11-26 | 2018-05-04 | 来安县杭姑娘生态农业有限公司 | A kind of special soilless culture substrate of lightweight cucumber |
| CN107950350A (en) * | 2017-11-26 | 2018-04-24 | 来安县杭姑娘生态农业有限公司 | A kind of cucumber soilless culture substrate full of nutrition |
| CN107889722A (en) * | 2017-11-26 | 2018-04-10 | 来安县杭姑娘生态农业有限公司 | A kind of soilless culture substrate for improving cucumber yield |
| CN107711417A (en) * | 2017-11-26 | 2018-02-23 | 来安县杭姑娘生态农业有限公司 | A kind of cheap cucumber soilless culture substrate of cost |
| CN108066817A (en) * | 2017-12-06 | 2018-05-25 | 常州琨瑶纺织品有限公司 | A kind of nano bone repair material and preparation method thereof |
| CN110038158A (en) * | 2019-05-27 | 2019-07-23 | 中国人民解放军第四军医大学 | The formula and preparation method thereof of photocuring 3D printing Haversian system artificial bone scaffold |
| US11357891B2 (en) * | 2019-06-14 | 2022-06-14 | Geistlich Pharma Ag | Collagen matrix or granulate blend of bone substitute material |
| CN110408087A (en) * | 2019-08-05 | 2019-11-05 | 中国科学技术大学 | A kind of bionic ceramic sill and preparation method thereof based on the optimization of nanoscale overstrain |
| CN111346262A (en) * | 2020-03-17 | 2020-06-30 | 四川大学 | Injectable calcium-phosphorus ceramic for promoting healing of tendon and bone and preparation method and application thereof |
| CN111346262B (en) * | 2020-03-17 | 2022-02-01 | 四川大学 | Injectable calcium-phosphorus ceramic for promoting healing of tendon and bone and preparation method and application thereof |
| CN112043873A (en) * | 2020-09-16 | 2020-12-08 | 浙江甬誉生物科技有限公司 | Organic polymer bridging-containing bio-inorganic composite structure material and preparation method and application thereof |
| CN112745142A (en) * | 2021-03-04 | 2021-05-04 | 四川大学 | Graphene/calcium phosphate ceramic composite bracket with antibacterial function and preparation method thereof |
| CN113041398A (en) * | 2021-03-16 | 2021-06-29 | 上海大学绍兴研究院 | High-entropy ceramic composite collagen material, preparation method and application thereof, and high-entropy ceramic composite collagen artificial bone |
| CN114712557A (en) * | 2022-04-02 | 2022-07-08 | 中山大学附属口腔医院 | Hydrogel reinforced biological bone calcium apatite scaffold and manufacturing method thereof |
| CN115177787A (en) * | 2022-07-29 | 2022-10-14 | 奥精医疗科技股份有限公司 | 3D printing composite bone repair material and preparation method and application thereof |
| CN115252891A (en) * | 2022-08-26 | 2022-11-01 | 四川大学 | Preparation method of calcium phosphate ceramic for drug loading and drug loading method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103055352B (en) | 2014-12-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103055352B (en) | Calcium phosphate/collagen composite biologic ceramic material and preparation method thereof | |
| Dorozhkin | Calcium orthophosphate-based bioceramics | |
| CN100546661C (en) | A kind of preparation method of in situ pore-forming self-setting calcium phosphate composite tissue engineering scaffold | |
| Dorozhkin | Medical application of calcium orthophosphate bioceramics | |
| CN103599561B (en) | A kind of preparation method of magnesium alloy/hydroxyapatite composite | |
| CN110141687B (en) | Gradient material for guiding regeneration of periodontal hard and soft tissues and preparation method thereof | |
| CN103341206B (en) | Calcium phosphate/collagen/bone-like apatite three-level bionic bone tissue engineering scaffold and preparation method thereof | |
| CN101564553B (en) | Humanization active forging bone and preparation method thereof | |
| CN103585677B (en) | A kind of HA micro-nano whisker reinforcement calcium phosphate ceramic material and its preparation method and application | |
| Weir et al. | Culture human mesenchymal stem cells with calcium phosphate cement scaffolds for bone repair | |
| CN102302804B (en) | Hydroxyapatite-based biological composite scaffold and tissue engineered bone | |
| Li et al. | Fabrication of individual scaffolds based on a patient-specific alveolar bone defect model | |
| JP5406915B2 (en) | Biocompatible implant | |
| CN102512267A (en) | Bone restoration body with composite porous structure and preparation method thereof | |
| CN101461963A (en) | Multiplex composite bone tissue engineering bracket material capable of degrading gradiently and preparation method thereof | |
| CN106348785A (en) | Bioactive porous ceramic tubular bar material as well as preparation method and application thereof | |
| CN105521525B (en) | A kind of bone tissue engineer porous compound support frame and preparation method thereof | |
| CN102008752B (en) | Porous biphasic calcium phosphate biological scaffold with nano hydroxyapatite coating and preparation method thereof | |
| CN110051881A (en) | A kind of 3D printing nanometer silver antimicrobial bone renovating material and preparation method thereof | |
| CN107235721A (en) | A kind of porous Bredigites biological ceramic support of 3 D-printing and preparation method and application | |
| Zhang et al. | Surface-treated 3D printed Ti-6Al-4V scaffolds with enhanced bone regeneration performance: An in vivo study | |
| CN105999418B (en) | A kind of injectable type bioactive bone cement material and preparation method thereof | |
| CN1460526A (en) | Porous bone prosthesis containing hydroxy apatite component and its preparation method | |
| Rahaman et al. | Bioactive glass in bone tissue engineering | |
| Dorozhkin | Calcium orthophosphate (CaPO4)–based bone-graft substitutes and the special roles of octacalcium phosphate materials |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20141210 Termination date: 20160122 |
|
| EXPY | Termination of patent right or utility model |