CN105797217A - Porous micro-sphere bone repair material and preparing method thereof - Google Patents
Porous micro-sphere bone repair material and preparing method thereof Download PDFInfo
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Abstract
The invention provides a porous micro-sphere bone repair material and a preparing method thereof, and relates to the technical field of medical materials.The preparing method includes the steps that based on the bionic theory, degradable high polymer materials, apatite, collagen and bone morphogenetic protein are used as raw materials, and the degradable-high-polymer-material-coating porous micro-sphere bone repair material prepared from the degradable high polymer materials, the apatite, the collagen and the bone morphogenetic protein is formed according to the certain technology.The porous micro-sphere bone repair material has the ingredients and the fine structure similar to the human bone, has good bone conduction performance and good bone induction performance, can be degraded and absorbed, and can serve as the excellent bone repair material to be applied to the field of the bone surgery, the plastic surgery and the dentistry.
Description
Technical field
The present invention relates to medical material technical field, specifically refer to a kind of bone renovating material with porous microsphere structure and preparation method thereof.
Background technology
More typically, thus for a long time, the reparation of defect skeleton is always up the vital task of bone research to the osseous tissue defect caused due to factors such as wound, tumor, infection, pathology clinically.Restorative procedure conventional at present, as autologous bone transplanting, allogenic bone transplantation, synthetic substitute materials all have problems to a certain extent.Autologous bone transplanting is by the restriction of Self Donor finiteness, and second operation brings misery to patient；Allogenic bone transplantation is primarily present immunity rejection, has the possibility causing infecting disease and tumor generation；Other various artificial bone substitute materials using metal, pottery or macromolecule manufacture have also been applied to clinic but majority is to use as permanent implant, material non-degradable, it is impossible to participating in the metabolism of human body, Regenerated Bone can not be carried out by bone remoulding in defective region.Therefore, existing bone grafting material is all improved or studies in effort, develop invention bone renovating material by researcheres.Desirable bone impairment renovation material should have good histocompatibility, wide material sources, safe and reliable, there is bone conduction and self-bone grafting performance, there is plasticity, and it is biodegradable, can decompose gradually in stoping forming process, not affect the 26S Proteasome Structure and Function of cambium.
Body bone tissue is considered the class material assembled with the collagen fiber of mineralising for elementary cell classification, the solvent constituting bone includes the calcium phosphorus system's mineral based on apatite and the organic substrate composition based on collagen protein, osseous tissue there is also three-dimensional through pore structure, nutrient delivery and cell activities is most important.
Therefore, the present invention proposes a kind of bone renovating material based on bionic theory.
Summary of the invention
For the deficiencies in the prior art, the present invention proposes a kind of porous microsphere bone renovating material, this bone renovating material can solve existing bone renovating material non-degradable, the problems such as Regenerated Bone can not be carried out in defective region by bone remoulding, this bone renovating material has the composition similar with people's bone and fine structure simultaneously, possesses good bone conduction and self-bone grafting performance.
For above-mentioned porous microsphere bone renovating material, present invention also offers a kind of preparation technology, the simple preparation method of required condition.
To achieve these goals, the technical solution used in the present invention is as follows:
The present invention proposes a kind of porous microsphere bone renovating material, including degradable high polymer material, apatite, collagen and bone morphogenetic protein, described degradable high polymer material, apatite, collagen and bone morphogenetic protein are formed with degradable high polymer material for wall material, the porous microsphere structure being core with apatite, collagen and bone morphogenetic protein, described degradable high polymer material cladding apatite, collagen and bone morphogenetic protein, wherein, described degradable high polymer material is Poly(D,L-lactide-co-glycolide；Described apatite is hydroxyapatite；Described collagen be the one in NTx and II Collagen Type VI or in combination with.
Meanwhile, the present invention also proposes a kind of method preparing porous microsphere bone renovating material, comprises the following steps:
S100, apatite/collagen composite materials preparation:
A1, the addition of C acl2 solution is joined the phosphoric acid solution of collagen, be stirring evenly and then adding intoSolution, the pH value adjusting solution is 7 ± 0.2；
A2, above-mentioned solution is stirred, and reacts at normal temperatures 8～12 hours, be precipitated thing；
A3, above-mentioned solution, control the consumption of each material, it is ensured that the mass ratio of the apatite being ultimately formed and collagen is 50/40～80/20；
A4, with deionized water, above-mentioned precipitate is washed three times, then place in freeze dryer and carry out lyophilization, prepare apatite/collagen composite materials.
S200, porous microsphere bone renovating material preparation:
B1, a certain amount of degradable high polymer material is joined in dichloromethane or chloroform or acetone or other mixed solvents and dissolves, prepare mixed solution,
B2, in above-mentioned mixed solution, add in step S100 obtained apatite/collagen composite materials and bone morphogenetic protein to form suspension solution, i.e. oil phase；
B3, to take PVA aqueous solution be dispersion phase and aqueous phase, is joined by oil phase in aqueous phase, after continuous stirring reaction certain time, stops stirring；
B4, standing overnight, are precipitated, and precipitation cyclic washing is prepared porous microsphere bone renovating material after drying；
Wherein, in mixed solution, the concentration of degradable high polymer material is 0.05～0.5g/ml, it is 5%～20% that apatite/collagen composite materials accounts for the mass fraction of degradable high polymer material, it is 0.5%～5% that bone morphogenetic protein accounts for the mass fraction of degradable high polymer material, the volume ratio of oil phase and aqueous phase is 1:25～1:200, the concentration of PVA aqueous solution is 0.005～0.1g/ml, and mixing speed is 200～800r/min.
Beneficial effects of the present invention:
1. porous microsphere bone renovating material proposed by the invention has the composition similar with people's bone and fine structure, good bone conduction and self-bone grafting performance, and degradable absorbs, and can be applied to Orthopeadic Surgery, plastic surgery and dental field as outstanding bone renovating material；
2. material therefor of the present invention designs based on biomimetic concept, and apatite carries out ordered arrangement in collagen, simulates skeleton structure, has good histocompatibility and mechanical strength；
3. the porous microsphere structure that degradable high polymer material cladding is formed is that osteocyte provides growing space, the bone morphogenetic protein simultaneously comprised in porous microsphere structure has good induced osteogenesis effect, the self-reparing capability of skeleton can be greatly reinforced, in addition, degradable high polymer material can be decomposed into carbon dioxide and water with body metabolism after completing bone growth reparation, does not affect the 26S Proteasome Structure and Function of cambium.
Detailed description of the invention
For making the purpose of the embodiment of the present invention, technical scheme and advantage clearly, below in conjunction with the embodiment of the present invention, the technical scheme in the embodiment of the present invention is clearly and completely described, obviously, described embodiment is a part of embodiment of the present invention, rather than whole embodiments.Based on the embodiment in the present invention, the every other embodiment that those of ordinary skill in the art obtain under not making creative work premise, broadly fall into the scope of protection of the invention.
As described in background, artificial bone substitute materials is applied to clinic but majority is to use as permanent implant, material non-degradable, it is impossible to participating in the metabolism of human body, Regenerated Bone can not be carried out by bone remoulding in defective region.Based on this, the present invention proposes a kind of porous microsphere bone renovating material and preparation method thereof.
Above-mentioned porous microsphere bone renovating material is based on bionic theory, the present invention adopts degradable high polymer material, apatite, collagen and bone morphogenetic protein to be raw material, forms the porous microsphere material of the degradable high polymer material/apatite/collagen/bone morphogenetic protein of degradable high polymer material cladding then through the preparation of certain technique.Specifically, above-mentioned porous microsphere material includes degradable high polymer material, apatite, collagen and bone morphogenetic protein, described degradable high polymer material, apatite, collagen and bone morphogenetic protein are formed with degradable high polymer material for wall material, the porous microsphere structure being core with apatite, collagen and bone morphogenetic protein, described degradable high polymer material cladding apatite, collagen and bone morphogenetic protein, wherein, preferably, described degradable high polymer material is Poly(D,L-lactide-co-glycolide；Described apatite is hydroxyapatite；Described collagen be the one in NTx and II Collagen Type VI or in combination with；Described bone morphogenetic protein be the one in BMP-2 and BMP-7 or in combination with.
The present invention also proposes a kind of method preparing porous microsphere bone renovating material, comprises the following steps:
S100, apatite/collagen composite materials preparation:
A1, the addition of C acl2 solution is joined the phosphoric acid solution of collagen, be stirring evenly and then adding intoSolution, the pH value adjusting solution is 7 ± 0.2；
A2, above-mentioned solution is stirred, and reacts at normal temperatures 8～12 hours, be precipitated thing；
A3, above-mentioned solution, control the consumption of each material, it is ensured that the mass ratio of the apatite being ultimately formed and collagen is 50/40～80/20；
A4, with deionized water, above-mentioned precipitate is washed three times, then place in freeze dryer and carry out lyophilization, prepare apatite/collagen composite materials.
S200, porous microsphere bone renovating material preparation:
B1, a certain amount of degradable high polymer material is joined in dichloromethane or chloroform or acetone or other mixed solvents and dissolves, prepare mixed solution,
B2, in above-mentioned mixed solution, add in step S100 obtained apatite/collagen composite materials and bone morphogenetic protein to form suspension solution, i.e. oil phase；
B3, to take PVA aqueous solution be dispersion phase and aqueous phase, is joined by oil phase in aqueous phase, after continuous stirring reaction certain time, stops stirring；
B4, standing overnight, are precipitated, and precipitation cyclic washing is prepared porous microsphere bone renovating material after drying；
Wherein, in mixed solution, the concentration of degradable high polymer material is 0.05～0.5g/ml, it is 5%～20% that apatite/collagen composite materials accounts for the mass fraction of degradable high polymer material, it is 0.5%～5% that bone morphogenetic protein accounts for the mass fraction of degradable high polymer material, the volume ratio of oil phase and aqueous phase is 1:25～1:200, the concentration of PVA aqueous solution is 0.005～0.1g/ml, and mixing speed is 200～800r/min.
Technical scheme is illustrated below in conjunction with embodiment.
Embodiment one
The material that the present embodiment adopts is Poly(D,L-lactide-co-glycolide (PLGA), hydroxyapatite, NTx and BMP-2, first prepare hydroxyapatite/NTx composite, then with PLGA for wall material, PVA aqueous solution is dispersant, hydroxyapatite/NTx composite and BMP-2 are core, adopt solvent evaporated method to prepare PLGA/ hydroxyapatite/NTx/BMP-2 porous microsphere.Obtained micro-sphere material diameter is 50～700Between, surface is due to the much tiny hole of solvent volatile oil.Concrete, comprise the following steps:
The preparation of S100, hydroxyapatite/NTx composite:
A1, the addition of C acl2 solution is joined the phosphoric acid solution of NTx, be stirring evenly and then adding intoSolution, the pH value adjusting solution is 7 ± 0.2；
A2, above-mentioned solution is stirred, and reaction 8 hours at normal temperatures, it is precipitated thing；
A3, above-mentioned solution, control the consumption of each material, it is ensured that the mass ratio of the apatite being ultimately formed and collagen is 50/40；
A4, with deionized water, above-mentioned precipitate is washed three times, then place in freeze dryer and carry out lyophilization, prepare apatite/NTx composite.
The preparation of S200, PLGA/ hydroxyapatite/NTx/BMP-2 porous microsphere bone renovating material:
B1, a certain amount of PLGA is joined in dichloromethane or chloroform or acetone or other mixed solvents and dissolves, prepare mixed solution,
B2, in above-mentioned mixed solution, add in step S100 obtained hydroxyapatite/NTx composite and BMP-2 to form suspension solution, i.e. oil phase；
B3, to take PVA aqueous solution be dispersion phase and aqueous phase, is joined by oil phase in aqueous phase, after continuous stirring reaction certain time, stops stirring；
B4, standing overnight, are precipitated, and precipitation cyclic washing is prepared PLGA/ hydroxyapatite/NTx/BMP-2 porous microsphere bone renovating material after drying；
Wherein, in mixed solution, the concentration of PLGA is 0.05g/ml, it is 5% that apatite/collagen composite materials accounts for the mass fraction of degradable high polymer material, it is 0.5% that bone morphogenetic protein accounts for the mass fraction of degradable high polymer material, the volume ratio of oil phase and aqueous phase is 1:25, the concentration of PVA aqueous solution is 0.005g/ml, and mixing speed is 200r/min
Embodiment two
The material that the present embodiment adopts is Poly(D,L-lactide-co-glycolide (PLGA), hydroxyapatite, NTx and BMP-2, first prepare hydroxyapatite/NTx composite, then with PLGA for wall material, PVA aqueous solution is dispersant, hydroxyapatite/NTx composite and BMP-2 are core, adopt solvent evaporated method to prepare PLGA/ hydroxyapatite/NTx/BMP-2 porous microsphere.Obtained micro-sphere material diameter is 50～700Between, surface is due to the much tiny hole of solvent volatile oil.Concrete, comprise the following steps:
The preparation of S100, hydroxyapatite/NTx composite:
A1, the addition of C acl2 solution is joined the phosphoric acid solution of NTx, be stirring evenly and then adding intoSolution, the pH value adjusting solution is 7 ± 0.2；
A2, above-mentioned solution is stirred, and reaction 10 hours at normal temperatures, it is precipitated thing；
A3, above-mentioned solution, control the consumption of each material, it is ensured that the mass ratio of the apatite being ultimately formed and collagen is 70/30；
A4, with deionized water, above-mentioned precipitate is washed three times, then place in freeze dryer and carry out lyophilization, prepare apatite/NTx composite.
The preparation of S200, PLGA/ hydroxyapatite/NTx/BMP-2 porous microsphere bone renovating material:
B1, a certain amount of PLGA is joined in dichloromethane or chloroform or acetone or other mixed solvents and dissolves, prepare mixed solution,
B2, in above-mentioned mixed solution, add in step S100 obtained hydroxyapatite/NTx composite and BMP-2 to form suspension solution, i.e. oil phase；
B3, to take PVA aqueous solution be dispersion phase and aqueous phase, is joined by oil phase in aqueous phase, after continuous stirring reaction certain time, stops stirring；
B4, standing overnight, are precipitated, and precipitation cyclic washing is prepared PLGA/ hydroxyapatite/NTx/BMP-2 porous microsphere bone renovating material after drying；
Wherein, in mixed solution, the concentration of PLGA is 0.1g/ml, it is 10% that apatite/collagen composite materials accounts for the mass fraction of degradable high polymer material, it is 1% that bone morphogenetic protein accounts for the mass fraction of degradable high polymer material, the volume ratio of oil phase and aqueous phase is 1:50, the concentration of PVA aqueous solution is 0.01g/ml, and mixing speed is 400r/min.
Embodiment three
The material that the present embodiment adopts is Poly(D,L-lactide-co-glycolide (PLGA), hydroxyapatite, II Collagen Type VI and BMP-7, first prepare hydroxyapatite/II Collagen Type VI composite, then with PLGA for wall material, PVA aqueous solution is dispersant, hydroxyapatite/II Collagen Type VI composite and BMP-7 are core, adopt solvent evaporated method to prepare PLGA/ hydroxyapatite/II Collagen Type VI/BMP-7 porous microsphere.Obtained micro-sphere material diameter is 50～700Between, surface is due to the much tiny hole of solvent volatile oil.Concrete, comprise the following steps:
S100, hydroxyapatite/II Collagen Type VI composite preparation:
A1, the addition of C acl2 solution is joined the phosphoric acid solution of II Collagen Type VI, be stirring evenly and then adding intoSolution, the pH value adjusting solution is 7 ± 0.2；
A2, above-mentioned solution is stirred, and reaction 12 hours at normal temperatures, it is precipitated thing；
A3, above-mentioned solution, control the consumption of each material, it is ensured that the mass ratio of the apatite being ultimately formed and collagen is 70/20；
A4, with deionized water, above-mentioned precipitate is washed three times, then place in freeze dryer and carry out lyophilization, prepare hydroxyapatite/II Collagen Type VI composite.
The preparation of S200, PLGA/ hydroxyapatite/II Collagen Type VI/BMP-7 porous microsphere bone renovating material:
B1, a certain amount of PLGA is joined in dichloromethane or chloroform or acetone or other mixed solvents and dissolves, prepare mixed solution,
B2, in above-mentioned mixed solution, add in step S100 obtained hydroxyapatite/II Collagen Type VI composite and BMP-7 to form suspension solution, i.e. oil phase；
B3, to take PVA aqueous solution be dispersion phase and aqueous phase, is joined by oil phase in aqueous phase, after continuous stirring reaction certain time, stops stirring；
B4, standing overnight, are precipitated, and precipitation cyclic washing is prepared PLGA/ hydroxyapatite/II Collagen Type VI/BMP-7 porous microsphere bone renovating material after drying；
Wherein, in mixed solution, the concentration of PLGA is 0.3g/ml, it is 15% that apatite/collagen composite materials accounts for the mass fraction of degradable high polymer material, it is 2% that bone morphogenetic protein accounts for the mass fraction of degradable high polymer material, the volume ratio of oil phase and aqueous phase is 1:100, the concentration of PVA aqueous solution is 0.02g/ml, and mixing speed is 500r/min.
Embodiment four
The material that the present embodiment adopts is Poly(D,L-lactide-co-glycolide (PLGA), hydroxyapatite, II Collagen Type VI and BMP-7, first prepare hydroxyapatite/II Collagen Type VI composite, then with PLGA for wall material, PVA aqueous solution is dispersant, hydroxyapatite/II Collagen Type VI composite and BMP-7 are core, adopt solvent evaporated method to prepare PLGA/ hydroxyapatite/II Collagen Type VI/BMP-7 porous microsphere.Obtained micro-sphere material diameter is 50～700Between, surface is due to the much tiny hole of solvent volatile oil.Concrete, comprise the following steps:
S100, hydroxyapatite/II Collagen Type VI composite preparation:
A1, the addition of C acl2 solution is joined the phosphoric acid solution of II Collagen Type VI, be stirring evenly and then adding intoSolution, the pH value adjusting solution is 7 ± 0.2；
A2, above-mentioned solution is stirred, and reaction 12 hours at normal temperatures, it is precipitated thing；
A3, above-mentioned solution, control the consumption of each material, it is ensured that the mass ratio of the apatite being ultimately formed and collagen is 80/20；
A4, with deionized water, above-mentioned precipitate is washed three times, then place in freeze dryer and carry out lyophilization, prepare hydroxyapatite/II Collagen Type VI composite.
The preparation of S200, PLGA/ hydroxyapatite/II Collagen Type VI/BMP-7 porous microsphere bone renovating material:
B1, a certain amount of PLGA is joined in dichloromethane or chloroform or acetone or other mixed solvents and dissolves, prepare mixed solution,
B2, in above-mentioned mixed solution, add in step S100 obtained hydroxyapatite/II Collagen Type VI composite and BMP-7 to form suspension solution, i.e. oil phase；
B3, to take PVA aqueous solution be dispersion phase and aqueous phase, is joined by oil phase in aqueous phase, after continuous stirring reaction certain time, stops stirring；
B4, standing overnight, are precipitated, and precipitation cyclic washing is prepared PLGA/ hydroxyapatite/II Collagen Type VI/BMP-7 porous microsphere bone renovating material after drying；
Wherein, in mixed solution, the concentration of PLGA is 0.5g/ml, it is 20% that apatite/collagen composite materials accounts for the mass fraction of degradable high polymer material, it is 5% that bone morphogenetic protein accounts for the mass fraction of degradable high polymer material, the volume ratio of oil phase and aqueous phase is 1:200, the concentration of PVA aqueous solution is 0.1g/ml, and mixing speed is 800r/min.
The above; being only the specific embodiment of the present invention, but protection scope of the present invention is not limited thereto, any those familiar with the art is in the technical scope that the invention discloses; change can be readily occurred in or replace, all should be encompassed within protection scope of the present invention.Therefore, protection scope of the present invention should described be as the criterion with scope of the claims.
Claims (2)
1. a porous microsphere bone renovating material, it is characterized in that, including degradable high polymer material, apatite, collagen and bone morphogenetic protein, described degradable high polymer material, apatite, collagen and bone morphogenetic protein are formed with degradable high polymer material for wall material, the porous microsphere structure being core with apatite, collagen and bone morphogenetic protein, described degradable high polymer material cladding apatite, collagen and bone morphogenetic protein, wherein
Described degradable high polymer material is Poly(D,L-lactide-co-glycolide；
Described apatite is hydroxyapatite；
Described collagen be the one in NTx and II Collagen Type VI or in combination with；
Described bone morphogenetic protein be the one in BMP-2 and BMP-7 or in combination with.
2. the preparation method of a porous microsphere bone renovating material, it is characterised in that comprise the following steps:
S100, apatite/collagen composite materials preparation:
A1, the addition of C acl2 solution is joined the phosphoric acid solution of collagen, be stirring evenly and then adding intoSolution, the pH value adjusting solution is 7 ± 0.2；
A2, above-mentioned solution is stirred, and reacts at normal temperatures 8～12 hours, be precipitated thing；
A3, above-mentioned solution, control the consumption of each material, it is ensured that the mass ratio of the apatite being ultimately formed and collagen is 50/40～80/20；
A4, with deionized water, above-mentioned precipitate is washed three times, then place in freeze dryer and carry out lyophilization, prepare apatite/collagen composite materials；
S200, porous microsphere bone renovating material preparation:
B1, a certain amount of degradable high polymer material is joined in dichloromethane or chloroform or acetone or other mixed solvents and dissolves, prepare mixed solution,
B2, in above-mentioned mixed solution, add in step S100 obtained apatite/collagen composite materials and bone morphogenetic protein to form suspension solution, i.e. oil phase；
B3, to take PVA aqueous solution be dispersion phase and aqueous phase, is joined by oil phase in aqueous phase, after continuous stirring reaction certain time, stops stirring；
B4, standing overnight, are precipitated, and precipitation cyclic washing is prepared porous microsphere bone renovating material after drying；
Wherein, in mixed solution, the concentration of degradable high polymer material is 0.05～0.5g/ml, it is 5%～20% that apatite/collagen composite materials accounts for the mass fraction of degradable high polymer material, it is 0.5%～5% that bone morphogenetic protein accounts for the mass fraction of degradable high polymer material, the volume ratio of oil phase and aqueous phase is 1:25～1:200, the concentration of PVA aqueous solution is 0.005～0.1g/ml, and mixing speed is 200～800r/min.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107684637A (en) * | 2017-07-17 | 2018-02-13 | 大连理工大学 | A kind of polylactic acid/hydroxy apatite/de- cell amnion compound rest and its construction method |
| CN108096636A (en) * | 2017-12-22 | 2018-06-01 | 北京奥精医药科技有限公司 | PLA abutments section bone meal and preparation method thereof |
| CN108339158A (en) * | 2017-01-24 | 2018-07-31 | 中南民族大学 | The method and its application in Bone Defect Repari that one step builds two calcium phosphate phase microcapsules |
| CN110898252A (en) * | 2019-12-10 | 2020-03-24 | 河南亚都实业有限公司 | Bone repair material containing protein collagen base |
| CN117209806A (en) * | 2023-09-20 | 2023-12-12 | 深圳聚生生物科技有限公司 | Controllable microsphere preparation process capable of being used for medical 3D printing |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004071547A1 (en) * | 2003-02-12 | 2004-08-26 | Ethicon Gmbh | Bone filling material comprising anabolic steroid |
| CN102205150A (en) * | 2011-05-19 | 2011-10-05 | 清华大学 | Preparation method for anti-infectious nano collagen/ calcium phosphate bone repair material |
| CN102525940A (en) * | 2011-11-30 | 2012-07-04 | 江苏大学 | Inorganic/organic composite protein/polypeptide medicament sustained release microspheres and preparation method thereof |
| US20130273135A1 (en) * | 2008-03-25 | 2013-10-17 | University Of Utah Research Foundation | Controlled Release Combination Biomaterials |
| CN103751116A (en) * | 2014-01-06 | 2014-04-30 | 华南理工大学 | Preparation method of gentamicin sulphate-loading porous hydroxyapatite/PLGA (poly(DL-lactide-co-glycolide) microspheres |
| CN103768658A (en) * | 2012-10-18 | 2014-05-07 | 上海纳米技术及应用国家工程研究中心有限公司 | Hydroxyapatite-loading polylactic acid porous microsphere and preparation method thereof |
| CN105031727A (en) * | 2015-07-03 | 2015-11-11 | 深圳大学 | Drug loaded composite bone restoration material and preparation method thereof |
-
2016
- 2016-03-15 CN CN201610145018.XA patent/CN105797217A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004071547A1 (en) * | 2003-02-12 | 2004-08-26 | Ethicon Gmbh | Bone filling material comprising anabolic steroid |
| US20130273135A1 (en) * | 2008-03-25 | 2013-10-17 | University Of Utah Research Foundation | Controlled Release Combination Biomaterials |
| CN102205150A (en) * | 2011-05-19 | 2011-10-05 | 清华大学 | Preparation method for anti-infectious nano collagen/ calcium phosphate bone repair material |
| CN102525940A (en) * | 2011-11-30 | 2012-07-04 | 江苏大学 | Inorganic/organic composite protein/polypeptide medicament sustained release microspheres and preparation method thereof |
| CN103768658A (en) * | 2012-10-18 | 2014-05-07 | 上海纳米技术及应用国家工程研究中心有限公司 | Hydroxyapatite-loading polylactic acid porous microsphere and preparation method thereof |
| CN103751116A (en) * | 2014-01-06 | 2014-04-30 | 华南理工大学 | Preparation method of gentamicin sulphate-loading porous hydroxyapatite/PLGA (poly(DL-lactide-co-glycolide) microspheres |
| CN105031727A (en) * | 2015-07-03 | 2015-11-11 | 深圳大学 | Drug loaded composite bone restoration material and preparation method thereof |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108339158A (en) * | 2017-01-24 | 2018-07-31 | 中南民族大学 | The method and its application in Bone Defect Repari that one step builds two calcium phosphate phase microcapsules |
| CN107684637A (en) * | 2017-07-17 | 2018-02-13 | 大连理工大学 | A kind of polylactic acid/hydroxy apatite/de- cell amnion compound rest and its construction method |
| CN107684637B (en) * | 2017-07-17 | 2019-06-21 | 大连理工大学 | A kind of polylactic acid/hydroxy apatite/de- cell amnion compound rest and its construction method |
| CN108096636A (en) * | 2017-12-22 | 2018-06-01 | 北京奥精医药科技有限公司 | PLA abutments section bone meal and preparation method thereof |
| CN108096636B (en) * | 2017-12-22 | 2021-07-02 | 奥精医疗科技股份有限公司 | PLA-based dental bone powder and preparation method thereof |
| CN110898252A (en) * | 2019-12-10 | 2020-03-24 | 河南亚都实业有限公司 | Bone repair material containing protein collagen base |
| CN110898252B (en) * | 2019-12-10 | 2022-02-01 | 河南亚都实业有限公司 | Bone repair material containing protein collagen base |
| CN117209806A (en) * | 2023-09-20 | 2023-12-12 | 深圳聚生生物科技有限公司 | Controllable microsphere preparation process capable of being used for medical 3D printing |
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