CN108939156B - 3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold and preparation method thereof - Google Patents
3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a 3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold and a preparation method thereof. The 3D printed Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold is prepared from Ti6Al4V powder by a 3D printing technology, has controllable appearance, pore microstructure and physicochemical properties, is adhered with biological factor BMP-2 with bone repair capacity by polydopamine on the fiber surface, and can be used for repairing and treating bone defects. The invention has the advantages of simple and reliable structure, controllable appearance and microstructure, simple, convenient and efficient surface modification, reliable mechanical property, high bioactivity and safety, convenient implantation, small wound and low cost.
Description
Technical Field
The invention belongs to the field of bone tissue repair and reconstruction, and relates to a 3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold and a preparation method thereof.
Background
The repair and reconstruction of bone defects is one of the problems facing orthopedic clinics. As is well known, autologous bone is considered the gold standard for bone grafting, but its source is limited and may lead to complications such as necrosis of the supply site, chronic pain after surgery, allergic reactions and infections. While allogeneic and xenogeneic bones are widely used due to their wide source and lack of additional surgical procedures, there are complications of slow integration and remodeling, immune rejection and disease transmission, especially reduced osteoinductive and osteoconductive properties of the graft.
At present, the scaffold materials comprise bioactive calcium phosphate ceramics, Calcium Phosphate Cement (CPC), Hydroxyapatite (HA), coral and gypsum; polylactic acid (PLA), polyglycolic acid (PGA); collagen, Demineralized Bone Matrix (DBM), Fibrin Clot (FC), and the like. The ideal bone matrix material has the following conditions that (1) the bone matrix material has good biocompatibility, no toxic or side effect exists in the body after the bone matrix material is implanted into the body, no inflammatory reaction is generated, and graft rejection reaction of a host is not caused. (2) The degradation rate of the material must match the rate of new bone formation and the material can be completely absorbed after the scaffolding has been completed. (3) Has three-dimensional structure with porosity of at least more than 90 percent and certain toughness, and provides a high ratio of contact surface area and growth space for tissue cells. (4) The material can not only maintain the cell shape and phenotype, but also promote cell adhesion and proliferation and induce tissue regeneration. Although porous ceramic materials, polymer materials and their composite materials, etc. which are currently studied can be used as potential bone graft scaffold materials, they all have various disadvantages, and particularly, cannot meet the requirements of bone tissue repair at a load-bearing part. In recent years, the potential application of metal scaffolds with three-dimensional porous structures has attracted the attention of more and more researchers, and the metal scaffolds with three-dimensional porous structures are widely used in the fields of orthopedics and dentistry as a promising bone graft material. Metals are suitable for load-bearing applications due to their higher mechanical strength and fracture toughness compared to ceramics and polymer materials. Among many metal materials, titanium and its alloys are widely used due to their advantages such as good biocompatibility, biosafety, good mechanical properties, and corrosion resistance.
However, titanium metal as a scaffold material also has a problem of low biological activity, and therefore, many studies based on modification of the material itself and compounding of growth factors related to seed cells and osteogenesis and resorption have been carried out at present. The modification of the material mainly depends on the treatment of physicochemical factors, including acid-base treatment, and other elements are introduced in an electromagnetic and redox mode so as to expect to improve the biological activity of the stent. These methods are complex in the stent preparation process and uniformity is difficult to control. While seed cells are a key issue for tissue engineered bone. Ideal seed cells have the advantages of easily obtained materials and small damage to organisms; easy in vitro amplification and stable expression; implanted into the body has no immunological rejection, and has strong osteogenesis capacity and no tumorigenicity. At present, many researches are carried out on osteoblasts, bone marrow stromal cells, mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells and the like. However, for metal scaffolds, the lower cell carrying rate is still a bottleneck that hinders further development. As for the growth factors, Bone Morphogenetic Proteins (BMP), transforming growth factor- β (TGF- β), insulin-like growth factor (IGF), basic fibroblast growth factor (fgf), platelet-derived growth factor (PDGF), Vascular Endothelial Growth Factor (VEGF), and the like have been found to be known as related to osteogenesis. However, the biological safety of the bioactive factors is not guaranteed due to the existence of immunological rejection, pathogen transmission, anaphylactic reaction, potential tumorigenesis and teratogenic possibility, and clinical-grade biological factors such as rhBMP-2 and TGF-beta are imported and expensive, and the purchase price of each milligram reaches nearly thousands of dollars.
In conclusion, the development of the tissue engineering bone which has simple and reliable structure, proper mechanical strength, convenient operation implantation, small human body trauma, low cost and capability of inducing bone growth to repair and treat the bone defect has important practical significance for the development of the health industry of China and the construction of innovative countries.
Disclosure of Invention
The invention aims to provide a 3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold aiming at the defects in the prior art.
The invention also aims to provide a preparation method of the 3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold.
The purpose of the invention can be realized by the following technical scheme:
A3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold is composed of a 3D printing Ti scaffold with a porous structure prepared by a 3D printing technology of Ti6Al4V, a PDA coating on the fiber surface of the Ti scaffold and BMP-2 adsorbed on the surface of the PDA coating.
The 3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold is prepared by sintering Ti6Al4V powder into a formed fiber bundle preferably by a laser sintering technology and preparing the 3D printing Ti scaffold by splicing frameworks of different layers and angles of the fiber bundle; then under a certain condition, enabling dopamine to be polymerized on the fiber surface of the 3D printing Ti stent to form a PDA coating, thereby preparing the 3D printing Ti-PDA stent; and finally, loading BMP-2 on the surface of the PDA coating by the obtained 3D printed Ti-PDA scaffold through a method of adsorbing biological factors, and preparing the 3D printed Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold.
The 3D printed fibers are of a porous structure formed by layer-by-layer accumulation and splicing of different layers and angles, pores are formed by intersecting and accumulating the fibers of all layers within the range of 0-180 degrees, regular pores such as a 0-90-degree orthogonal line structure and a 0-60-120-degree triangular structure are formed finally, or a gradient and hierarchical intersection structure is formed according to actual needs.
According to the preparation method of the 3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold, Ti6Al4V powder is sintered into a formed fiber bundle by a laser sintering technology, and the 3D printing Ti scaffold is prepared by splicing frameworks of different layers and angles of the fiber bundle; then under a certain condition, enabling dopamine to be polymerized on the fiber surface of the 3D printing Ti stent to form a PDA coating, thereby preparing the 3D printing Ti-PDA stent; and finally, loading BMP-2 on the surface of the PDA coating by the obtained 3D printed Ti-PDA scaffold through a method of adsorbing biological factors, and preparing the 3D printed Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold.
The preparation method of the invention preferably comprises the following steps:
(1) preparing a 3D printing Ti support
(2) Preparing a 3D printing Ti-PDA bracket: preparing a DA-Tris-HCL solution, wherein the concentration of dopamine is 2g/L-8g/L, adding a 3D printing Ti bracket into the solution, stirring in a dark and unsealed state, taking out the bracket after DA self-polymerizes on the surface of Ti fibers to form PDA, and obtaining the 3D printing Ti-PDA bracket;
(3) preparing a 3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold: soaking the prepared 3D printed Ti-PDA bracket in BMP-2 aqueous solution containing 25 or 50 or 100 microgram/mL, fixing the prepared 3D printed Ti-PDA bracket on the surface of a matrix by virtue of the adsorption effect of phenolic hydroxyl and nitrogen-containing groups contained in PDA on the surface of the 3D printed Ti-PDA bracket on BMP-2 in the solution, taking out the bracket after soaking for 8, 16 or 24 hours, and realizing the Ti-PDA-BMP-2 bone defect repair tissue engineering bracket with different concentrations.
The specific method for preparing the 3D printing Ti support in the step (1) further preferably comprises the steps of forming a formed fiber bundle by laser sintering Ti6Al4V powder, and obtaining a 3D printing product by splicing frameworks of different layers and angles of the fiber bundle; the shape of the scaffold is manufactured individually by 3D printing according to the bone defect shapes of different areas to be repaired, or manufactured into a scaffold material with fixed shape by the SLM technology.
The pores of the 3D printing Ti support are regular pores with a 0-90-degree orthogonal line structure, or special gradient and hierarchical intersecting structures are formed according to actual needs.
Has the advantages that:
(1) controllable property of microstructure: the invention is a porous structure which is formed by building laser sintered fibers through layer-by-layer accumulation and splicing at different levels and angles, each layer of fibers in pores can be intersected and accumulated within the range of 0-180 degrees, the distance between every two fibers can also influence the size of the pores, thus regular pores with various cross structures can be formed finally, and special gradient and hierarchical intersection structures can also be formed according to actual needs; thus realizing the fine control of the appearance and the internal pore structure;
(2) the surface modification is simple and convenient and the biological factor slow release characteristic is as follows: the 3D printing microstructure provided by the invention can regulate and control the cell adhesion performance of the scaffold by the pore size, pore shape, pore orientation, porosity and connectivity of the scaffold, rough surface characteristics of the scaffold and the like. And the surface modification is carried out by adopting polydopamine, so that the hydrophilicity and the biocompatibility of the metal stent are not only simply and conveniently but also obviously improved. The adsorption effect of polydopamine can improve the carrying efficiency of growth factors and can realize the slow release of biological factors, and meanwhile, the loading capacity of the biological factors on the surface of the stent can be further regulated and controlled by changing the reaction time of PDA, the concentration of the biological factors and the adsorption time of the biological factors in the manufacturing process, so that the release characteristics of the biological factors are regulated and controlled.
(3) The adjustable and controllable characteristics of mechanical property, good bone ingrowth characteristic and biological safety are as follows: according to the porous microstructure, the Ti alloy material has a good elastic modulus and is positioned between the elastic moduli of the cortical bone and the cancellous bone of a human body, the mechanical environment of a region to be repaired can be matched accurately, and the growing and shaping of a new bone can be facilitated according to the Wolf law of bone growth; moreover, Ti itself has good biocompatibility, which can provide a local microenvironment favorable for stem cell adhesion, expansion, osteogenic differentiation and bone matrix accumulation. Meanwhile, modification of polydopamine can further improve the hydrophilicity and biocompatibility of the surface of the stent. The carried biological factors can be slowly released, so that a long-time efficient repair process of a defect area is realized, and meanwhile, the porous structure is favorable for exchanging nutrient components, so that the growth of new bones can be promoted. The Ti metal material adopted by the invention is widely applied to clinical use of the orthopaedic implant, polydopamine and BMP-2 are proved to be safe, the biological safety of the whole repair system is obviously higher than that of other modification schemes, and the osteogenesis activity is obviously improved.
The novel 3D printing Ti-PDA-BMP-2 bone defect repairing tissue engineering scaffold provided by the invention has the advantages of the existing bone repairing material, and also fully exerts the performances of the 3D printing technology and the scaffold material, so that the novel 3D printing Ti-PDA-BMP-2 bone defect repairing tissue engineering scaffold has the advantages of simple and reliable structure, controllable appearance and microstructure, simple, convenient and efficient surface modification, reliable mechanical property, high bioactivity and safety, convenience in implantation, small wound and low cost, and can be used for repairing and treating bone wounds, bone tumors and bone defects after bone infection.
Drawings
FIG. 1 is a technical route chart for bone repair by 3D printing of a Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold according to the present invention.
For a patient with bone defect, in addition to removing interference factors such as metal foreign matters which may influence a CT scanning image, anatomical data is obtained through CT scanning, and a 3D printing support with personalized appearance and physicochemical characteristics is designed and implanted into a bone defect area in combination with the severity of the condition of the bone defect. For patients who cannot obtain accurate anatomical data, 3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffolds which are prepared in advance is used, and the number of implanted scaffolds is determined according to actual defect conditions. And after the stent is implanted, new bone tissues continuously grow into the stent, and finally the aim of repairing the bone defect is fulfilled.
FIG. 2 is a schematic representation of the fiber lay-up arrangement of the present invention, creating a three-dimensional porous structure.
Fig. 2AB is a two-dimensional schematic diagram of the stacked arrangement of scaffold fibers at different levels, and it can be seen that the pore morphology of the scaffold is determined by the stacking of scaffold fibers, including pore size, pore shape, pore orientation, porosity, connectivity, and the like. Fig. 2C is a schematic diagram providing a 3D printed Ti stent with squares formed using a 0-90 stacked arrangement.
Fig. 3 provides a schematic structural view of a 3D printed Ti stent with a triangular shape formed using a 0-60-120 ° stacked arrangement. In actual work, the scaffold with personalized design and specific pore microstructure can be prepared by regulating and controlling the fiber lamination of the scaffold according to the actual requirements of mechanical environments, bone defect degrees and the like of different areas to be repaired.
Fig. 4 is a schematic diagram of a technical route for preparing a stent by adopting a generalized design and a 3D printing technology according to the present invention.
1 is Ti6Al4V powder; 2, preparing a 3D printing Ti support by powder through laser sintering; 3, performing PDA coating on the obtained Ti support to prepare a 3D printing Ti-PDA support; 4, mixing the 3D printed Ti-PDA bracket with a solution containing BMP-2 to prepare a 3D printed Ti-PDA-BMP-2 bone defect repair tissue engineering bracket; and 5, obtaining the universal 3D printed Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold.
FIG. 5 is a schematic view showing that the implant of the present invention can promote the growth of bone tissue into a bone defect region.
1 is normal bone tissue; 2, implanting the bracket into the bone defect part; 3, a schematic diagram for displaying biological factors on a single bracket fiber after the 3D printing of the Ti bracket is locally amplified; 4, releasing various factors of the Ti scaffold fiber; 5, releasing factors on the surface and in the scaffold, recruiting osteoblasts and growing bone tissues; and 6, the bone defect area is gradually repaired along with the growth of bone tissues and the integration of the bone tissues with the peripheral area.
FIG. 6 is a graph of a Ti stent real object printed at 0-90 degrees in 3D and a general photograph of the Ti stent real object modified by polydopamine. C. D is a real object diagram of the structural scaffold with the angle of 0-60-120 degrees and a general picture modified by dopamine.
FIG. 7 is a graph showing the results of an in vivo bone repair experiment according to the present invention.
A is a bone defect region; b, implanting the support into the bone defect area, and displaying that the 3D printing support is completely embedded into the bone defect area; c, the bone tissue gradually grows after the stent is implanted for 1 month; D. and E is a picture of the bracket implanted for 2 months and 3 months respectively, and shows the growth of the new bone tissue.
Detailed Description
Example 1
1. Preparing a 3D printing Ti support
The Ti6Al4V powder was laser sintered to form a shaped fiber bundle, a 3D printed Ti scaffold obtained by stacking and splicing the fiber bundle at 0-90 ° or 0-60-120 °, as shown in fig. 6.
2. Preparing 3D printing Ti-PDA bracket
After the scaffold structure is constructed through 3D printing, surface modification is carried out by using PDA, and the method specifically comprises the following steps:
1) preparing a hydrochloric acid (HCL) solution with the concentration of 0.5 mol/L;
2) weighing 0.61g of Tris, adding the Tris into 500ml of water for dissolving, stirring, dropwise adding the solution of prepared 0.5mol/L HCL into the solution of prepared 0.5mol/L HCL until the pH value is 8.5, and preparing a Tris-HCL solution for later use;
3) dissolving Dopamine (DA) in the 150ml Tris-HCl solution, stirring and dissolving to prepare 2% DA-Tris-HCl solution;
4) and adding the 3D printing Ti support into the solution, stirring in a dark and unsealed state at 800-.
3. Preparing 3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold
Soaking the prepared 3D printed Ti-PDA bracket in BMP-2 aqueous solution containing 25 or 50 or 100 mu g/mL, fixing the prepared 3D printed Ti-PDA bracket on the surface of a matrix by virtue of the adsorption effect of phenolic hydroxyl and nitrogen-containing groups contained in PDA on the surface of the Ti-PDA bracket on BMP-2 in the solution, taking out the bracket after soaking for 8, 16 or 24 hours, and realizing the Ti-PDA-BMP-2 bone defect repair tissue engineering bracket with different concentrations, as shown in figure 6.
The prepared 3D-printed Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold was surgically implanted into the bone defect area of rabbits, and the results are shown in fig. 7.
Claims (5)
1. A3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold is characterized in that Ti6Al4V powder is sintered into a molded fiber bundle by a laser sintering technology, and the 3D printing Ti scaffold is prepared by splicing frameworks of different layers and angles of the fiber bundle; then under a certain condition, enabling dopamine to be polymerized on the fiber surface of the 3D printing Ti stent to form a PDA coating, thereby preparing the 3D printing Ti-PDA stent; and finally, loading BMP-2 on the surface of the PDA coating by the obtained 3D printed Ti-PDA scaffold through a method of adsorbing biological factors, and preparing the 3D printed Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold.
2. The 3D printed Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold of claim 1, wherein the 3D printed fibers are formed into a porous structure by layer-by-layer accumulation and splicing of different layers and angles, the pores are formed by intersecting and accumulating fibers of each layer within the range of 0-180 degrees, and finally regular pores such as 0-90 degree orthogonal row structure or 0-60-120 degree triangular structure are formed, or gradient and hierarchical intersecting structures are formed according to actual needs.
3. The 3D printed Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold according to claim 1, characterized in that it is prepared by the following method:
(1) preparing a 3D printing Ti support
(2) Preparing a 3D printing Ti-PDA bracket: preparing a DA-Tris-HCL solution, wherein the concentration of dopamine is 2g/L-8g/L, adding a 3D printing Ti bracket into the solution, stirring in a dark and unsealed state, taking out the bracket after DA self-polymerizes on the surface of Ti fibers to form PDA, and obtaining the 3D printing Ti-PDA bracket;
(3) soaking the prepared 3D printed Ti-PDA bracket in BMP-2 aqueous solution containing 25 or 50 or 100 mu g/mL, fixing the prepared 3D printed Ti-PDA bracket on the surface of a matrix by virtue of the adsorption effect of phenolic hydroxyl and nitrogen-containing groups contained in PDA on the surface of the 3D printed Ti-PDA bracket on BMP-2 in the solution, taking out the bracket after soaking for 8, 16 or 24 hours, and realizing the Ti-PDA-BMP-2 bone defect repair tissue engineering bracket with different concentrations.
4. The preparation method according to claim 3, wherein the 3D printing Ti support is prepared in the step (1) by forming a shaped fiber bundle from Ti6Al4V powder by laser sintering, and obtaining a 3D printing product by splicing structures of different layers and angles of the fiber bundle; the shape of the scaffold is manufactured individually by 3D printing according to the bone defect shapes of different areas to be repaired, or manufactured into a scaffold material with fixed shape by the SLM technology.
5. The preparation method according to claim 4, wherein the pores of the 3D printed Ti scaffold are regular pores with 0-90 ° orthogonal row structure or 0-60-120 ° triangular structure, or are formed into special gradient and hierarchical intersecting structures according to actual needs.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011139996.6A CN112107726A (en) | 2018-06-15 | 2018-06-15 | Preparation method of 3D-printed Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold |
| CN201810616827.3A CN108939156B (en) | 2018-06-15 | 2018-06-15 | 3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810616827.3A CN108939156B (en) | 2018-06-15 | 2018-06-15 | 3D printing Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold and preparation method thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011139996.6A Division CN112107726A (en) | 2018-06-15 | 2018-06-15 | Preparation method of 3D-printed Ti-PDA-BMP-2 bone defect repair tissue engineering scaffold |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108939156A CN108939156A (en) | 2018-12-07 |
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| CN109568674A (en) * | 2018-12-28 | 2019-04-05 | 上海纳米技术及应用国家工程研究中心有限公司 | Carry preparation method of the bionical bone repair porous scaffold of Types of Medicine and products thereof and application |
| CN110403736A (en) * | 2019-08-09 | 2019-11-05 | 常州市第二人民医院 | A kind of super porous titanium alloy of 3D printing facilitates bone surface method of modifying |
| CN111643725B (en) * | 2020-06-01 | 2021-05-07 | 四川大学 | Artificial bone material for repairing bone defect and preparation method of artificial bone particles |
| CN113476658A (en) * | 2021-07-16 | 2021-10-08 | 北京理工大学重庆创新中心 | Bessel beam-based bone joint implant surface treatment method |
| CN114099778A (en) * | 2021-09-30 | 2022-03-01 | 上海市浦东新区人民医院 | Composite scaffold for bone tissue engineering |
| CN114515356B (en) * | 2022-03-11 | 2023-02-10 | 福州大学 | Preparation method of bionic bone tissue engineering scaffold capable of resisting inflammation and promoting bone defect repair |
| CN116175956A (en) * | 2023-01-05 | 2023-05-30 | 北京大学 | Preparation method of attachable tissue engineering scaffold material based on suspension printing technology |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3454513A (en) * | 1965-07-30 | 1969-07-08 | Martin V Azarian | Metal powders coated with silica and a water soluble acetate |
| CN101889912A (en) * | 2010-08-05 | 2010-11-24 | 上海交通大学 | Preparation method of bio-ceramic coating titanium-wire sintering porous titanium artificial bone |
| CN102058904A (en) * | 2010-12-31 | 2011-05-18 | 重庆大学 | Biological functionalized nano titanium material and preparation method thereof |
| CN103060590A (en) * | 2013-01-08 | 2013-04-24 | 西北工业大学 | Preparation method of gradient porous titanium alloy |
| CN103751840A (en) * | 2014-02-12 | 2014-04-30 | 吴志宏 | Porous, controllable and low-modulus bone defect repair bracket and preparation method thereof |
| CN106270517A (en) * | 2016-08-16 | 2017-01-04 | 华中科技大学 | A kind of network structure part preparation method with composition gradient transitional lay double with hole |
| CN107349472A (en) * | 2017-06-30 | 2017-11-17 | 浙江德康医疗器械有限公司 | A kind of preparation method of the gradient porous titanium alloy of repetition of promotion bone fusion |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106474541B (en) * | 2015-08-31 | 2019-07-19 | 华东理工大学 | A kind of tissue engineering bracket of 3D and preparation method thereof |
| CN107029304A (en) * | 2016-10-24 | 2017-08-11 | 北京大学口腔医院 | Biological planting body and the method that active factors is prepared on matrix |
-
2018
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Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3454513A (en) * | 1965-07-30 | 1969-07-08 | Martin V Azarian | Metal powders coated with silica and a water soluble acetate |
| CN101889912A (en) * | 2010-08-05 | 2010-11-24 | 上海交通大学 | Preparation method of bio-ceramic coating titanium-wire sintering porous titanium artificial bone |
| CN102058904A (en) * | 2010-12-31 | 2011-05-18 | 重庆大学 | Biological functionalized nano titanium material and preparation method thereof |
| CN103060590A (en) * | 2013-01-08 | 2013-04-24 | 西北工业大学 | Preparation method of gradient porous titanium alloy |
| CN103751840A (en) * | 2014-02-12 | 2014-04-30 | 吴志宏 | Porous, controllable and low-modulus bone defect repair bracket and preparation method thereof |
| CN106270517A (en) * | 2016-08-16 | 2017-01-04 | 华中科技大学 | A kind of network structure part preparation method with composition gradient transitional lay double with hole |
| CN107349472A (en) * | 2017-06-30 | 2017-11-17 | 浙江德康医疗器械有限公司 | A kind of preparation method of the gradient porous titanium alloy of repetition of promotion bone fusion |
Non-Patent Citations (2)
| Title |
|---|
| 《Fabrication and Mechanical Characterisation of Titanium Lattices with Graded Porosity》;William van Grunsven et al;《Metals》;20140814;第4卷(第3期);第401-409页 * |
| 《基于增材制造技术的钛合金医用植入物》;周梦等;《中国科学: 技术科学》;20161031;第46卷(第11期);第1097-1115页 * |
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| CN112107726A (en) | 2020-12-22 |
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