CN102430151B - Tissue engineering bone cartilage composite bracket and integrated photocuringable forming method thereof - Google Patents
Tissue engineering bone cartilage composite bracket and integrated photocuringable forming method thereof Download PDFInfo
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- CN102430151B CN102430151B CN2011102605306A CN201110260530A CN102430151B CN 102430151 B CN102430151 B CN 102430151B CN 2011102605306 A CN2011102605306 A CN 2011102605306A CN 201110260530 A CN201110260530 A CN 201110260530A CN 102430151 B CN102430151 B CN 102430151B
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Abstract
The invention discloses a tissue engineering bone cartilage composite bracket and an integrated photocuringable forming method thereof. The tissue engineering bone cartilage composite bracket serves as a ceramic bracket, wherein the ceramic bracket is served as a bone-repair part, and a porous structure is arranged on the surface of the ceramic bracketbone-repair part of the porous structure; and the ceramic bracket is fixed on a supporting plate of a photocuringable quick forming machine. A laser scanning path is driven through a computer aided design (CAD) model; and laser directly exposes and cures a hydrogel bracket and a pure hydrogel bracket which contain a ceramic component onto the ceramic bracket sequentially to form a three-layer composite bracket. Therefore, quick and fine preparation of a three-dimensional composite bracket of bone cartilage-like tissue histomorphometry is realized; uncontrollable structures and low efficiency because of handwork in the preparation process of a traditional composite bracket are avoided; the preparation efficiency is improved; and a calcified cartilage-like layer bracket and a hydrogel cartilage bracket with subtle structures can be bonded and compounded on the surface of the ceramic bracket by means of a rivet and a two-phase material.
Description
Technical field
The present invention relates to the Biotechnology field, particularly tissue engineered bone cartilage compound rest and integrated optical curing molding method thereof.
Background technology
Because the self-reparing capability of adult's articular cartilage is limited, damaged for articular cartilage and bone, need surgical intervention usually clinically, comprises microfrature under Arthroscopic debridement, mirror, the autotransplantation of bone cartilage etc.The defects such as it is poor that above-mentioned means exist repairing effect, is limited to patient age and damaged area, and the graft source is limited.By in recent years, to the research of artificial bone cartilage defect repair, the osteochondral tissue engineering had had more deep development, and demonstrated the tremendous potential of application clinically.
The osteochondral tissue engineering rack includes simple bone (cartilage) support, bone cartilage compound rest and the kinds such as bone cartilage compound rest that comprise the calcified cartilage layer, most bone cartilage compound rest mainly relies on manual suture, the mode such as bonding to prepare, the operating process complexity, automatization and customization degree are low, and cause the structural instability of compound rest, after implanting, support easily produces delamination, the situation such as peel off, can't for cambium grow into and the fusion of support and surrounding tissue provides a good mechanics back-up environment.In addition, there is one deck calcified cartilage layer between the natural bone cartilage, it plays the carrying of cartilage pressure and the effect that stops vascular invasion supported, this transition structure of preparation calcified cartilage layer support is not considered in the preparation of conventional stent, and that hierarchy support prepared by the method that adopts 3 D-printing exists adhesion is poor, the support problem such as easily subside after implanting.
Summary of the invention
In order to overcome the defect of above-mentioned prior art, the object of the present invention is to provide tissue engineered bone cartilage compound rest and integrated optical curing molding method thereof, can prepare fast the osteochondral tissue engineering MULTILAYER COMPOSITE support that customizes profile, compound rest has the calcification layer of similar calcified cartilage layer function, rely on the hole of ceramic bone surface and colloid in surperficial bonding effect, can effectively improve the adhesive strength between compound rest, strengthen the stability after support is implanted, for growing into of cell and tissue provides a good mechanics back-up environment, it is high that this preparation method has precision, simple to operate, cycle is short, repeatable high advantage.
In order to achieve the above object, technical scheme of the present invention is achieved in that
A kind of integrated optical curing molding method of tissue engineered bone cartilage compound rest comprises the following steps:
Step 3, adopt the light-sensitive material polyethyleneglycol diacrylate, preparation is containing the hydrogel solution of ceramic powders, according to volume ratio by ceramic powders: polyethyleneglycol diacrylate: light trigger I-1173: deionized water=90: (30-50): (0.3-0.5): ratio (50-70) is evenly mixed, adopt ball mill ball milling 2-3 hour, be placed in type vacuum injecting and forming machine and remove bubble;
Step 4, adopt the light-sensitive material polyethyleneglycol diacrylate, the preparation hydrogel solution, according to volume ratio by polyethyleneglycol diacrylate: light trigger I-1173: deionized water=(30-50): (0.3-0.5): ratio (50-70) is evenly mixed, adopt magnetic stirrer to stir and at the uniform velocity stir 30-60min, be placed in type vacuum injecting and forming machine and remove bubble;
Step 5, ceramics bone frame is placed in to rapidform machine to have on the supporting plate of regulating calibrating installation, be placed in the prepared hydrogel solution containing ceramic powders of step 3, regulating ceramics bone frame aims at calcified cartilage layer support three-dimensional data profile, adjust the liquid level zero-bit, carry out hot spot scanning, the straight forming three dimensional structure;
Step 6, supporting plate is risen, to replace with containing the hydrogel solution of ceramic powders the prepared hydrogel solution of step 4, data are replaced by hydrogel cartilage support three-dimensional data, regulate ceramics bone frame and aim at calcified cartilage layer support three-dimensional data profile, adjust the liquid level zero-bit, carry out hot spot scanning, the straight forming three dimensional structure, make the MULTILAYER COMPOSITE support, be placed in deionized water repeatedly swelling, disinfect.
Described light trigger I-1173 is 2-hydroxy-2-methyl-1-phenyl-1-propyl group ketone.
Prepared tissue engineered bone cartilage MULTILAYER COMPOSITE support, comprise porous ceramics bone support 1, is solidified with the hydrogel support 2 containing ceramic component on porous ceramics bone support 1, containing on the hydrogel support 2 of ceramic component, is being solidified with pure water gel stent 3.
Porous ceramics bone support 1 surface has the pore structure on the similar natural bone surface of design in advance, be conducive to the infiltration of class calcified cartilage layer support in preparation process, and compound rest is implanted the rear limited infiltration of blood from ceramics bone frame to hydrogel cartilage support.
The mixture that the hydrogel support 2 that contains ceramic component is bioceramic and hydrogel, the formation of calcified cartilage layer tissue after can impelling compound rest to implant, play the effect of the calcified cartilage layer had between similar natural bone and cartilage, stop the intrusion of blood vessel from ceramics bone frame to hydrogel cartilage support, impel compound rest to implant the formation of rear cartilage.
Hydrogel cartilage support 3 solidify to form for the polyethyleneglycol diacrylate with biocompatibility, there is the curved-surface structure be complementary with implant site, after being convenient to compound rest and implanting and the coupling on natural joint surface, for the attaching of cell and the growth of tissue provide a good environment.
The present invention prepares on the basis of ceramics bone frame at rapid shaping, proposition be take the ceramics bracket surface as substrate, utilize Introduction To Stereolithography to prepare class calcified cartilage layer support and hydrogel cartilage support, realize the preparation of many Material claddings of multilamellar support, can prepare fast customization, bone cartilage MULTILAYER COMPOSITE support that bond strength is high, for the preparation of osteochondral tissue engineering compound rest provides customization, technique is simple, precision is high process.
The accompanying drawing explanation
Fig. 1 is process chart of the present invention.
Fig. 2 is ceramics bracket localization machine composition.
Fig. 3 is structural representation of the present invention, and wherein: Fig. 3 (a) is MULTILAYER COMPOSITE support front view; Fig. 3 (b) is the compound rest normal axomometric drawing.
Fig. 4 is the implant site schematic diagram of bone cartilage MULTILAYER COMPOSITE support.
The specific embodiment
Below in conjunction with accompanying drawing, the present invention is described in further detail.
With reference to Fig. 1, according to the Introduction To Stereolithography that utilizes of the present invention's proposition, the ceramics bracket prepared based on rapid shaping technique of take is substrate, relies on its porous surface, straight forming class calcified cartilage layer support and hydrogel cartilage support, and its concrete steps comprise:
A kind of integrated optical curing molding method of tissue engineered bone cartilage compound rest comprises the following steps:
Porous ceramics bone support 1 demand according to the support implant site, utilize three-dimensional reverse technology, extract the joint profile, through Geomagics and Pro/E software processes, design porous ceramics support, its upper surface profile is derived from the pass pitch surface, and has equally distributed at least 200 μ m holes, hole accounts for the 40-50% area, preparation prototype or minus; Class calcified cartilage layer backing thickness is 300 μ m, and hydrogel cartilage backing thickness is 1000 μ m, and threedimensional model saves as the .stl formatted file, adopts rapidform machine to prepare the ceramics bone frame minus, adopts gel casting process, prepares biscuit of ceramics; Perhaps adopt rapid shaping technique, directly solidify ceramic size, forming ceramic biscuit.Drying, the deresination technique such as come unstuck, high temperature sintering, prepare ceramics bone frame, or adopt additive method, and as the 3 D-printing method of forming, fusion sediment method etc. prepares ceramics bone frame.
Step 3, adopt the light-sensitive material polyethyleneglycol diacrylate, preparation is containing the hydrogel solution of ceramic powders, according to volume ratio by ceramic powders: polyethyleneglycol diacrylate: light trigger I-1173: deionized water=90: 40: 0.5: 60 ratio is evenly mixed, adopt ball mill ball milling 3 hours, be placed in type vacuum injecting and forming machine and remove bubble;
Step 4, adopt the light-sensitive material polyethyleneglycol diacrylate, the preparation hydrogel solution, according to volume ratio by polyethyleneglycol diacrylate: light trigger I-1173: the ratio of deionized water=40: 0.5: 60 is evenly mixed, adopt magnetic stirrer to stir and at the uniform velocity stir 50min, be placed in type vacuum injecting and forming machine and remove bubble;
Step 5, ceramics bone frame is placed in to rapidform machine to have on the supporting plate of regulating calibrating installation, be placed in the prepared hydrogel solution containing ceramic powders of step 3, regulating ceramics bone frame aims at calcified cartilage layer support three-dimensional data profile, adjust the liquid level zero-bit, carry out hot spot scanning, the straight forming three dimensional structure;
The specific embodiment of this step is: with reference to Fig. 2, adopt two-dimensional localization mechanism, by ceramics bone frame according to model the position in computer software magics and accurately being positioned on the rapid shaping machine supporting plate, adjust zero-bit, be placed in the prepared hydrogel solution containing ceramic powders of step 3, , carry out the scanning of class calcified cartilage layer data, the scanning process parameter is: solid state laser wavelength 355nm, spot diameter 0.20mm, model lift height 0.10mm, fill scanning speed 2500.00mm/s, fill vectorial spacing 0.10mm, support scanning speed 500mm/s, skip during preparation and support this step of scanning, across hop rate degree 12000.00mm/s, profile scan speed 3000mm/s, compensation diameter 0.1mm, worktable lifting speed 2.0mm/s, point supports 1.66ms sweep time, structure 1.37ms sweep time tangles,
Step 6, supporting plate is risen, to replace with containing the hydrogel solution of ceramic powders the prepared hydrogel solution of step 4, data are replaced by hydrogel cartilage support three-dimensional data, regulate ceramics bone frame and aim at calcified cartilage layer support three-dimensional data profile, adjust the liquid level zero-bit, carry out hot spot scanning, the straight forming three dimensional structure, make the MULTILAYER COMPOSITE support, be placed in deionized water repeatedly swelling, disinfect;
The specific embodiment of this step is: the rising supporting plate, solution is replaced with to the prepared hydrogel solution of step 4, data are replaced by hydrogel cartilage support three-dimensional data, regulating ceramics bone frame aims at calcified cartilage layer support three-dimensional data profile, adjust the liquid level zero-bit, the scanning of carrying out hydrogel cartilage support is solidified, the scanning process parameter is: solid state laser wavelength 355nm, spot diameter 0.20mm, model lift height 0.10mm, fill scanning speed 5500.00mm/s, fill vectorial spacing 0.10mm, support scanning speed 1000mm/s, skip during preparation and support this step of scanning, across hop rate degree 12000.00mm/s, profile scan speed 6000mm/s, compensation diameter 0.1mm, worktable lifting speed 2.0mm/s, point supports 0.50ms sweep time, structure 0.50ms sweep time tangles, after prepared by compound rest, take out, be placed in deionized water and clean, it is carried out to the processing such as follow-up sterilization, carry out external implantation.Now can adjust the two-dimensional localization mechanism position, the displacement ceramics bracket can repeat to prepare compound rest.
Light trigger I-1173 described in above-mentioned steps is 2-hydroxy-2-methyl-1-phenyl-1-propyl group ketone.
With reference to Fig. 3, prepared tissue engineered bone cartilage MULTILAYER COMPOSITE support, comprise porous ceramics bone support 1, be solidified with the hydrogel support 2 containing ceramic component on porous ceramics bone support 1, containing on the hydrogel support 2 of ceramic component, be solidified with pure water gel stent 3.
Fig. 4 is the distal femur position schematic diagram that the present invention implants new zealand rabbit, shows rack surface and articular surface SURFACES MATCHING in figure.
Claims (3)
1. the integrated optical curing molding method of a tissue engineered bone cartilage compound rest, is characterized in that, comprises the following steps:
Step 1, employing gel injection-moulding or Stereolithography technology prepare porous ceramics bone support (1), and porous ceramics bone support (1) surface uniform distributed aperture is not less than the hole of 200 μ m;
Step 2, according to the ceramics bone frame size, calcified cartilage layer support and cartilage frame threedimensional model that design matches, and be converted into the .stl formatted file, through delamination software, process, by data importing photocureable rapid shaping machine;
Step 3, adopt the light-sensitive material polyethyleneglycol diacrylate, preparation is containing the hydrogel solution of ceramic powders, according to volume ratio by ceramic powders: polyethyleneglycol diacrylate: light trigger I-1173: deionized water=90:(30-50): (0.3-0.5): ratio (50-70) is evenly mixed, adopt ball mill ball milling 2-3 hour, be placed in type vacuum injecting and forming machine and remove bubble;
Step 4, adopt the light-sensitive material polyethyleneglycol diacrylate, the preparation hydrogel solution, according to volume ratio by polyethyleneglycol diacrylate: light trigger I-1173: deionized water=(30-50): (0.3-0.5): ratio (50-70) is evenly mixed, adopt magnetic stirrer to stir and at the uniform velocity stir 30-60min, be placed in type vacuum injecting and forming machine and remove bubble;
Step 5, ceramics bone frame (1) is placed in to rapidform machine to have on the supporting plate of regulating calibrating installation, be placed in the prepared hydrogel solution containing ceramic powders of step 3, regulating ceramics bone frame aims at calcified cartilage layer support three-dimensional data profile, adjust the liquid level zero-bit, carry out hot spot scanning, the straight forming three dimensional structure;
Step 6, supporting plate is risen, to replace with containing the hydrogel solution of ceramic powders the prepared hydrogel solution of step 4, data are replaced by hydrogel cartilage support three-dimensional data, regulate ceramics bone frame and aim at calcified cartilage layer support three-dimensional data profile, adjust the liquid level zero-bit, carry out hot spot scanning, the straight forming three dimensional structure, make the MULTILAYER COMPOSITE support, be placed in deionized water repeatedly swelling, disinfect.
2. the integrated optical curing molding method of a kind of tissue engineered bone cartilage compound rest according to claim 1, is characterized in that, comprises the following steps:
Step 1, employing gel injection-moulding or Stereolithography technology prepare porous ceramics bone support (1), and porous ceramics bone support (1) surface uniform distributed aperture is not less than the hole of 200 μ m;
Porous ceramics bone support (1) is according to the demand of support implant site, utilize three-dimensional reverse technology, extract the joint profile, through Geomagics and Pro/E software processes, design porous ceramics support, its upper surface profile is derived from the pass pitch surface, and has equally distributed at least 200 μ m holes, hole accounts for the 40-50% area, preparation prototype or minus; Class calcified cartilage layer backing thickness is 300 μ m, and hydrogel cartilage backing thickness is 1000 μ m, and threedimensional model saves as the .stl formatted file, adopts rapidform machine to prepare the ceramics bone frame minus, adopts gel casting process, prepares biscuit of ceramics; Perhaps adopt rapid shaping technique, directly solidify ceramic size, the forming ceramic biscuit, drying, deresination degumming tech, high temperature sintering, prepare ceramics bone frame, or adopt the 3 D-printing method of forming, the standby ceramics bone frame of fusion sediment legal system;
Step 2, according to the ceramics bone frame size, calcified cartilage layer support and cartilage frame threedimensional model that design matches, and be converted into the .stl formatted file, through delamination software, process, by data importing photocureable rapid shaping machine;
Step 3, adopt the light-sensitive material polyethyleneglycol diacrylate, preparation is containing the hydrogel solution of ceramic powders, according to volume ratio by ceramic powders: polyethyleneglycol diacrylate: the ratio of light trigger I-1173: deionized water=90:40:0.5:60 is evenly mixed, adopt ball mill ball milling 3 hours, be placed in type vacuum injecting and forming machine and remove bubble;
Step 4, adopt the light-sensitive material polyethyleneglycol diacrylate, the preparation hydrogel solution, according to volume ratio by polyethyleneglycol diacrylate: the ratio of light trigger I-1173: deionized water=40:0.5:60 is evenly mixed, adopt magnetic stirrer to stir and at the uniform velocity stir 50min, be placed in type vacuum injecting and forming machine and remove bubble;
Step 5, ceramics bone frame is placed in to rapidform machine to have on the supporting plate of regulating calibrating installation, be placed in the prepared hydrogel solution containing ceramic powders of step 3, regulating ceramics bone frame aims at calcified cartilage layer support three-dimensional data profile, adjust the liquid level zero-bit, carry out hot spot scanning, the straight forming three dimensional structure;
The specific embodiment of this step is: adopt two-dimensional localization mechanism, by ceramics bone frame according to model the position in computer software magics and accurately being positioned on the rapid shaping machine supporting plate, adjust zero-bit, be placed in the prepared hydrogel solution containing ceramic powders of step 3, carry out the scanning of class calcified cartilage layer data, the scanning process parameter is: solid state laser wavelength 355nm, spot diameter 0.20mm, model lift height 0.10mm, fill scanning speed 2500.00mm/s, fill vectorial spacing 0.10mm, support scanning speed 500mm/s, skip during preparation and support this step of scanning, across hop rate 12000.00mm/s, profile scan speed 3000mm/s, compensation diameter 0.1mm, worktable lifting speed 2.0mm/s, point supports 1.66ms sweep time, structure 1.37ms sweep time tangles,
Step 6, supporting plate is risen, to replace with containing the hydrogel solution of ceramic powders the prepared hydrogel solution of step 4, data are replaced by hydrogel cartilage support three-dimensional data, regulate ceramics bone frame and aim at calcified cartilage layer support three-dimensional data profile, adjust the liquid level zero-bit, carry out hot spot scanning, the straight forming three dimensional structure, make the MULTILAYER COMPOSITE support, be placed in deionized water repeatedly swelling, disinfect;
The specific embodiment of this step is: the rising supporting plate, solution is replaced with to the prepared hydrogel solution of step 4, data are replaced by hydrogel cartilage support three-dimensional data, regulating ceramics bone frame aims at calcified cartilage layer support three-dimensional data profile, adjust the liquid level zero-bit, the scanning of carrying out hydrogel cartilage support is solidified, the scanning process parameter is: solid state laser wavelength 355nm, spot diameter 0.20mm, model lift height 0.10mm, fill scanning speed 5500.00mm/s, fill vectorial spacing 0.10mm, support scanning speed 1000mm/s, skip during preparation and support this step of scanning, across hop rate degree 12000.00mm/s, profile scan speed 6000mm/s, compensation diameter 0.1mm, worktable lifting speed 2.0mm/s, point supports 0.50ms sweep time, structure 0.50ms sweep time tangles, after prepared by compound rest, take out, be placed in deionized water and clean, it is carried out to follow-up disinfecting.
3. the integrated optical curing molding method of a kind of tissue engineered bone cartilage compound rest according to claim 1 and 2, is characterized in that, the light trigger I-1173 described in step is 2-hydroxy-2-methyl-1-phenyl-1-propyl group ketone.
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| CN103463676B (en) * | 2013-08-14 | 2016-01-20 | 西安交通大学 | A kind of bionic bone/cartilage composite scaffold and preparation technology thereof and fixing means |
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| CN103989541B (en) * | 2014-05-19 | 2016-04-27 | 西安交通大学 | There is the preparation method of the high strength composite bone cartilage frame of complex profile |
| CN103976805B (en) * | 2014-05-29 | 2016-03-30 | 西安交通大学 | The manufacture method of hydrogel/high molecular polymer thin film muscular tissue support |
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| BR112018007052B1 (en) * | 2015-10-09 | 2023-01-17 | Ossiform Aps | PROCESS FOR 3D PRINTING A THREE-DIMENSIONAL OBJECT |
| CN106421904B (en) * | 2016-09-19 | 2019-07-23 | 西安交通大学 | A kind of method that gel injection-moulding 3D printing and electroreduction prepare porous implant |
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| CN108478871B (en) * | 2018-04-17 | 2020-10-13 | 四川大学 | Integrated bone-cartilage repair scaffold and preparation method thereof |
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| CN110404108B (en) * | 2019-08-02 | 2021-11-23 | 武汉理工大学 | Double-layer bone-cartilage repair scaffold and preparation method thereof |
| WO2022126594A1 (en) * | 2020-12-18 | 2022-06-23 | 中国科学院深圳先进技术研究院 | Fractal scaffold construction method for bone tissue engineering |
| CN112957523B (en) * | 2021-02-09 | 2021-12-07 | 浙江大学 | Bionic composite stent for synchronously repairing soft and hard tissue defects and forming method based on 3D printing |
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