CN1654028A - Tissue engineering complex grid shape stent forming method base on core dissolving technology - Google Patents
Tissue engineering complex grid shape stent forming method base on core dissolving technology Download PDFInfo
- Publication number
- CN1654028A CN1654028A CNA2005100112281A CN200510011228A CN1654028A CN 1654028 A CN1654028 A CN 1654028A CN A2005100112281 A CNA2005100112281 A CN A2005100112281A CN 200510011228 A CN200510011228 A CN 200510011228A CN 1654028 A CN1654028 A CN 1654028A
- Authority
- CN
- China
- Prior art keywords
- support
- inner core
- mould
- core
- solution
- 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
Landscapes
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
The method of complicated tubular netted tissue engineering rack forming technology based on core dissolving technique belongs to the field of tissue engineering rack manufacturing technology. The technological process includes first designing 3D model of rack and rack core; making rack core with water soluble material without biotoxicity through fast laminated formation; compounding solution of biocompatible material with proper amount of pore creating agent and coating the solution onto the rack core; air drying, soaking in distilled water to dissolve out rack core and pore creating agent, taking out and volatilizing water and coating different forming material with or without pore creating agent successively to form the tubular netted rack with complicated spatial structure, different material gradient and different pore gradient.
Description
Technical field
The present invention relates to a kind of tissue engineering complex grid shape stent forming method, belong to the shaping manufacturing technology field of tissue engineering bracket.
Background technology
Tissue engineering bracket for the cell growth provides the material base and the mechanical support of adhering to, is the basis of carrying out Tissue Engineering Study as one of organizational project three elements.Human tissue engineering specification requirement support has excellent biological compatibility, degradability; Has suitable mechanical property; Have the macro morphology similar and certain micropore mechanism to Target organ.The macroshape of its medium-height trestle has determined artificial organ or the final shape of organ basically.Is need be the support of principal character with the pipe network structure all in the organizational project of organ of major function structure in digestive tubes such as nerve trachea reparation, blood vessel, salivary gland, organizational project, respiratory tract, urethra and reproductive tract etc. with hollow tubular.In addition, in complex organ organizational projects such as liver, kidney, also need to have the tubular bracket of complex space net architecture as the basis.The forming technique of tissue engineering tubular scaffold mainly can be divided three classes at present: a class is aided with simple and mechanical based on hand finishing; The special mechanical molding of one class; One class is based on the forming technique of discrete/accumulation principle.
Hand finishing is that the typical technology of main manufacturing process is as follows: with Glass rod or teflon rod is inner core, with polycaprolactone (PGA) nonwoven web on Glass rod or teflon rod, sew up or the bonded joint place, after by hand timbering material being peeled off from inner core, can obtain the hollow tubular support.
Also the someone adopts the glass molds general laws to make tubular bracket by hand.[Pan Yong, Huang Wei, Ai Yufeng, Bears is violent, Zhang Linxi, Peng is surge, the pre-structure of tissue engineering artificial intravascular stent, Chinese shaping surgery magazine, 2003 (1), Vol.19, P44-46.] this method adopts Glass rod as inner core, uses thicker glass tubing as external mold, with the two combination afterwards as mould.Polycaprolactone (PGA) nonwoven web is mixed with crosslinked collagen solution, pour in the mold cavity, 4 ℃ of refrigerator overnight, dry back is manual peels off timbering material from mould, can obtain support.
Operation is simple for the hand finishing method, can be used for simple straight tube and be shaped, and is used for the research of organizational project cell culture technology more.The simple straight-tube shape support but this method only can be shaped, can't embark on journey has the tubular bracket of bifurcation structure.Because need by hand material to be peeled off from Glass rod, so this method is to the stent forming difficulty small-bore, that length/diameter is bigger.Limited by mould, this method processing flexibility is poor.
Special-purpose machinery shaping typical process---extrusion molding method.[Markus S.Widmer, Puneet K.Gupta, LichunLu, etc.Manufacture of porous biodegradable polymer conduits by an extrusion processfor guided tissue regeneration, Biomaterials 1998 (19) P1945-1955.] this method typical process flow is as follows: 1) material preparation.PLLA or PLGA material are made dichloromethane solution, and in solution, add a certain proportion of sodium chloride particle as perforating agent, behind the mix homogeneously that solution is freezing, and remove with freeze-drying and to desolvate.Shred less than the fragment of 5mm the material after the lyophilizing standby.2) extrusion molding.With the material fragment extruder of packing into of preparation, extruder at first is heated to material more than the fusing point of PLLA or PLGA, extrudes from nozzle with certain speed then, obtains the tubulose blank.3) with the NaCl granule perforating agent in solvent (water) the stripping support, promptly obtain tubular bracket after the drying.The advantage of this method is the support good reproducibility, the forming efficiency height.Shortcoming is that the kind of this method moulding material is limited, and has pyroprocess in the processing, and is bigger to the material property influence, is unfavorable for keeping biology, the mechanical property of material.This method single tube that only can be shaped simultaneously, the complex grid with bifurcation structure that can't be shaped is support and has material gradient and the support of function gradient structure.In this method, the fusion of material require experience will have a negative impact to biocompatible polymer material.
Based on dispersing/pile up the typical process of the forming technique of principle---based on the negative norm casting [E.Sachlosa of 3 D-printing (3DP), N.Reisa, C.Ainsley, etc.Novel collagen scaffolds with predefinedinternal morphology made by solid freeform fabrication, Biomaterials 2003 (23), P1487-1497.].This method idiographic flow is as follows: 1) at first according to the cad model of the concrete shaped design negative norm tool of support, go up the prototype of making the negative norm tool at 3DP former Model-Maker II type equipment (U.S. Solidscape Inc. production) then.The prototype that obtains is immersed in the specific solvent, and the molten backing material that removes promptly obtains the negative norm tool behind the removal solvent.2) prepare the aqueous solution of collagen by certain requirements.Collagen solution is poured in the negative norm tool die cavity, and mould is put into-20 ℃ of refrigerator and cooled freeze.3) in-20 ℃ low temperature environment, refrigerated mould is put into alcoholic solution,, and slough ice crystal in the collagen-based materials negative norm tool dissolving.4) adopt the Freeze Drying Technique lyophilizing to be left collagen scaffold at last, remove the ethanol equal solvent, can obtain tissue engineering bracket.The advantage of the method is based on the 3 D-printing technology, has good forming accuracy and processing flexibility.The collagen-based materials but this method only can be shaped at present can't be formed in the synthetic macromolecular material that is most widely used in the organizational project.This method uses toxic material to make mould simultaneously, and material is residual to be can not be ignored the support performance impact.This method tube wall that can't be shaped equally has the tubular bracket of gradient-structure simultaneously.
In human tissue engineering, because the difference of destination organization or organ, and the difference of implementation method, to timbering material, performance demands such as the macro-size of support, microcellular structure, pore size, porosity, degradation cycle also have nothing in common with each other.For example, in the salivary gland tissues engineering that the Capital University of Medical Sciences carries out, require as follows to support: 1) porosity requires more than 85%, and micro-pore diameter is approximately 20～40 μ m, and has good connectivity between the micropore; 2) mechanical property: elastic strain is not less than 30%, and elastic modelling quantity is about 50～100KPa.3) about internal diameter 1mm, macro morphology is the straight tube of end sealing.And in the culturing in vivo scheme of intravascular tissue engineering, structure and mechanical property requirements to support are then more complicated: wish that 1) the tubular bracket wall construction can have and the similar laminated gradient structure of natural blood vessel wall, porosity, the pore size of each layer have nothing in common with each other; 2) good anticoagulation function; 3) support is pliable and tough, can resist more intrinsic pressure, good sewing properties, better elastic or the like.And in the organizational project of complex organs such as liver, kidney, the pipe network support that then more requires support to have the certain space network structure, the block support that perhaps has specific inner flow passage shape.
Total the above, organizational project is to multiformity and uncertainty that support requires, require the manufacturing process of support can be shaped multiple material, the support of can being shaped with complicated macro morphology, can be shaped has the manufacturing process of complicated microstructure.In the forming technique of present tissue engineering tubular scaffold, major defect is as follows:
(1) major defect of hand finishing method is the simple straight tubbiness support that only can be shaped, and to having the stent forming difficulty of big length/diameter ratio, more can't be shaped has the tubular bracket of bifurcation structure.This method processing flexibility is poor in addition, and the support repeatable accuracy is low.
(2) major defect of mechanical molding's method is can't be shaped to have the tubular bracket of bifurcation structure, and also can't be shaped has the multiple structure support, and the kind of this method formable material is limited, and the tube wall that also can't be shaped has the tubular bracket of gradient-structure.
(3) based on the negative norm casting of 3 D-printing (3DP), can be shaped and have the block support of inner flow passage structure, the major defect of this technology is as follows: 1) the moulding material kind is single, the collagen-based materials that only can be shaped at present, the synthetic macromolecular material that is most widely used in the present organizational project that can't be shaped.2) can't be shaped and have the support of material gradient and porosity gradient, and this technology relatively is suitable for being shaped and has the block support of specific inner flow passage, shaping thin-walled tubular bracket ability is relatively poor.3) employed mold materials has very strong bio-toxicity.Molten except that in the process at mould, the residual meeting of material causes adverse effect to the biocompatibility of support itself.
Summary of the invention
The present invention is directed to that the formable material kind that present tubular bracket technology exists is limited, can't be shaped has the cancellated tubular bracket in space and the tube wall that can't be shaped has the problem of the tubular bracket of material gradient and porosity gradient, has developed a kind of tissue engineering complex grid shape stent forming method based on soluble core technique.Purpose is for a kind of new stent forming method is provided, can satisfy structure and the performance requirement of organizational project to the support complexity, but the tubular bracket of formingspace pipe network structure or have the block support of interior pipe network structure, and the tube wall that can be shaped has the support of gradient-structure.
Technical scheme of the present invention is as follows:
A kind of tissue engineering complex grid shape stent forming method based on soluble core technique is characterized in that this method carries out as follows:
A), at first according to the spatial form and the support inner flow passage spatial form of support outline, utilize three-dimensional graphics software, the three-dimensional electronic model of design inner core or mould;
B), adopt inanimate object toxicity, water-soluble thermoplastic, utilize Rapid Prototyping technique, direct forming or indirectly forming step a) in the inner core or the mould of design;
C), the selected at least a examples of natural biocompatible materials that dissolves in the biocompatible polymer material of volatilizable organic solvent or be insoluble to neutral aqueous solution, with volatilizable solvent the biocompatible materials of selecting being mixed with mass volume ratio concentration respectively is 2%～20% serial solution;
D), in the serial solution that step (c) is prepared, add the water solublity porogen, biocompatible materials and porogen material are 1: 0～100 ratio adding by weight, and with the solution mix homogeneously; Described water solublity porogen adopts sodium chloride particle, ammonium bicarbonate granule, water solublity monosaccharide or disaccharidase granule.
E), adopt the process of spraying, infiltration, electrospinning silk or casting that the serial solution for preparing in the step d) is deposited on the interior core outer surface of formed thereby in the step b) in order uniformly; Perhaps serial solution is poured in the dies cavity; And by dry naturally, vacuum drying or cryodesiccated method make its solvent evaporates.Every kind of material deposition quantity requires decision by support tube wall specific performance.
F), inner core or the mould that obtains in the step e) immersed in the distilled water molten inner core and the porogen of removing; After support taken out, adopt that nature dries from distilled water, vacuum drying or cryodesiccated method vapor away the moisture in the support, promptly make grid shape stent or have the used in tissue engineering support of specific inner flow passage.
Inanimate object toxicity described in the step b), water-soluble thermoplastic adopt monosaccharide, disaccharidase, water soluble polysaccharide or its mixture.
The biocompatible polymer material that dissolves in volatilizable organic solvent described in the step c) adopts polylactic acid and polymer, poly-Acetic acid, hydroxy-, bimol. cyclic ester, polylactic acid-poly-glycolide copolymer, polycaprolactone, poly-beta-hydroxy-butanoic acid ester, gathers beta-hydroxy-butanoic acid ester-poly-hydroxyl pentanoate copolymer, polycaprolactone-polyethylene glycol segmented copolymer or polyurethane; The described examples of natural biocompatible materials that is insoluble to neutral aqueous solution adopts collagen.Described volatilizable organic solvent adopts a kind of or wherein several mixed system in halogenated hydrocarbons, ethyl acetate, dioxane, oxolane, chloroform or the dichloromethane.
Can add the powder of TCP or HA in the solution that can in step c), be prepared.
The direct forming method of inner core of support described in the step b) or mould adopts melted extrusion forming technology, selective laser sintering or three-dimensional printing-forming; Described indirect forming technique process is as follows: at first adopt the prototype parts of making based on Rapid Prototyping technique, turn over system silica gel mould, utilize silica gel mould to make inner core or mould then; Or directly use rapid prototyping technology to make master mold, use master mold to make inner core or mould then.
The present invention compared with prior art has the following advantages and the salience effect: the present invention adopts inanimate object toxicity, material soluble in water to make inner core and mould, solved that various toxic solvents have shortened technological process to the influence of timbering material biocompatibility in the residual and inner core removal process of inner core material.The present invention adopts Rapid Prototyping technique to come the shaped bracket inner core, and it is big that Rapid Prototyping technique has the processing capacitive, can according to cad model directly, the characteristics fast that are shaped, guaranteed that the present invention has the ability of the complicated support that is shaped, and can realize customized support manufacturing.The present invention's support that tube wall has material gradient and porosity gradient structure that can be shaped.Suitable material of the present invention is extensive simultaneously, and widely used multiclass high molecular polymer and collagen-based materials etc. all can use the present invention to be shaped in the organizational project at present.The present invention adopts spraying, immerse processes such as wrapping up in deposited, casting, electrospinning silk applies, is sprayed on core surface with multiple material solution by a graded, thereby realizes the layering of tubular bracket wall and porosity gradient, material gradient shaping.By the sedimentary order of control material, adjustment deposition process parameters, the radial material gradient of may command tube wall.By adjusting micropore forming parameters, the radial porosity gradient of may command tube wall.This manufacturing process, huge processing flexibility with Rapid Prototyping technique, mutually combine with existing comparatively sophisticated stent forming technology, and adopt inanimate object toxicity, water miscible material to make the support holder, can well satisfy in the organizational project support, particularly to material, structure and the mechanical performance of tubular bracket complexity and the complexity of bio-compatible performance, many-sided requirement.
Description of drawings
Fig. 1 is a processing technology flow chart of the present invention.
The bifurcated tubular bracket sketch map that Fig. 2 has three-decker for the tube wall that adopts the present invention to make.
Fig. 3 is the amplification of A part among Fig. 2.
Fig. 4 is pipe network core arrangement figure in the support.
The specific embodiment
Fig. 1 is the process chart of a kind of tissue engineering complex grid shape stent forming method based on soluble core technique provided by the invention.The inventive method at first needs to utilize three-dimensional graphics software, the three-dimensional electronic model of design inner core or mould.When making tubular bracket, core shape is determined by the tubular bracket inner chamber.When making has the support of inner flow passage,,, the two assembling back is used simultaneously according to inner flow passage shaped design inner core then at first according to support outline pattern design outer mold.After inner core or mould design are finished, utilize Rapid Prototyping technique, adopt inanimate object toxicity, water-soluble thermoplastic, direct forming or be shaped indirectly designed inner core or mould.The manufactured materials of present inner core of the present invention or mould is water solublity monosaccharide, disaccharidase, polysaccharide and composition thereof, as glucose, maltose, sucrose and fructose etc.The direct forming method can adopt melted extrusion forming technology, selective laser sintering or three-dimensional printing-forming.Forming technique can adopt following method to carry out indirectly: at first adopt the prototype parts of making based on Rapid Prototyping technique, turn over system silica gel mould, utilize silica gel mould to make inner core or mould then; Or directly use rapid prototyping technology to make master mold, use master mold to make inner core or mould then.
According to the requirement of support to material and mechanism, selected one or more tissue engineering bracket biocompatible materials, and material is dissolved in the volatile solvent are configured to mass volume ratio concentration and are 2%～20% serial solution.According to the requirement of support to micropore air strike rate, micropore size distribution and pore size, the water solublity perforating agent in selected certain proportion and certain footpath, and perforating agent is added in the serial solution of configuration mix homogeneously.The biocompatible materials of herein selecting for use, it promptly can be the polymeric material of synthetic, as the polymer of polylactic acid (PLA) and various configurations thereof, poly-Acetic acid, hydroxy-, bimol. cyclic ester (PGA claims polyglycolic acid again), polylactic acid-poly-glycolide copolymer (PLGA), polycaprolactone (PCL), poly-beta-hydroxy-butanoic acid ester (PHB), PHB-poly-hydroxyl valerate (PHV) copolymer, polycaprolactone (PCL)-Polyethylene Glycol (PEG) segmented copolymer or polyurethane (PU); Also can be the natural biological soluble materials that is insoluble to neutral water, as collagen.The volatile solvent that herein refers to can be a kind of or wherein several mixed system in halogenated hydrocarbons, ethyl acetate, dioxane, one or four dioxane, oxolane, chloroform or the dichloromethane; Also can be faintly acid or weak alkaline aqueous solution.After the solution preparation is finished, also can in solution, add TCP or HA powder to improve some performance of biocompatible materials.
After solution is purchased and finished, then material is deposited in core surface or the dies cavity by certain process sequence.In this step, first-selection need design the sedimentary order and the deposition of serial solution according to the distribution of material gradient in the tubular bracket wall and the distribution situation of porosity gradient.Then according to the order that realizes design, according to the quantity deposition materials of demand.During deposition materials, except that adopting means such as infiltration coating, spraying and casting commonly used, also can adopt electrospinning silk technology, to the core surface deposition materials.After the material deposition finishes, promptly obtain the blank that tube wall has the support of gradient-structure.The support blank that will have inner core and perforating agent at last immerses in the distilled water, molten inner core and mould and the perforating agent of removing.Support is taken out from distilled water, dry naturally or vacuum drying after, can obtain final support.
Embodiment 1:
Need to have the pipe network shape carrier tubular bracket of plane bifurcation structure in certain organizational project, its " trunk " locates maximum gauge is 3mm, and two bifurcation structures are arranged under the trunk, bifurcated diameter 3mm.The support tube wall has three-decker.Inwall needs the microcellular structure of aperture at 70um, and porosity is about 90%, and material is PLGA.Outer wall needs the microcellular structure of aperture at 120um, and porosity is about 75%, and material is identical with internal layer.Intermediate layer pore-free structure, material are the PCL-PET segmented copolymer.
(1) design support inner core.Use the three dimensional structure of SolidWorks three-dimensional CAD software design inner core, and the cad model of support inner core is output as the stl file form.
(2) employing melt extrudes technology (MEM technology) making inner core.The inner core moulding material is the mixture of maltose, glucose and sucrose.This material has good melted extrusion forming performance, and inanimate object toxicity is very easily water-soluble.On the MEM250-II type melted extrusion forming machine of Beijing Yin Hua laser fast forming and the production of Tool and Die Technology company limited, make the support inner core.Shape in the process at this inner core, the main technologic parameters of employing is: bed thickness 0.20mm, scanning speed 23mm/s.
(4) preparation shaping material solution.
Configuration solution a: with 4g PLGA (M η: 100,000) be dissolved in 50ml organic solvent one or four dioxane, be mixed with the polymer solution of 8% (wt/v).According to 9: 1 ratio of PLGA weight ratio, in solution, add through grinding, garbled particle diameter is at the NaCl of 60um～78um granule 36g, and stirs on magnetic stirrer, and is standby.
Configuration solution b: the PCL-PET copolymer of 3.0g is dissolved in 15ml by organic solvent, is mixed with the polymer solution of 20% (wt/v); The mixed liquor that organic solvent adopts one or four dioxane and oxolane to be mixed with in 5: 1 by volume.
Solution c: with 1.5g PLGA (M η: 100,000) be dissolved in 15ml organic solvent one or four dioxane, be mixed with the polymer solution of 10% (wt/v).According to NaCl and 3: 1 ratio of PLGA weight ratio, in solution, add, and on magnetic stirrer, stir through grinding, the NaCl granule of garbled particle diameter about 120 μ m, standby.
(5) wrap up in compress material.
The support inner core slowly, is vertically immersed among the solution a, inner core is slowly proposed, and it is suspended on the homemade rotator.Open rotator, allow the inner core natural air drying.After 15 minutes, repeat above-mentioned steps.By that analogy, on core surface, apply 6 layers of solution a.
Inner core is inserted ventilated chamber, air-dry 1 hour.
Adopt to wrap up in core surface in the same way and apply 4 layers of solution b.
Inner core is inserted ventilated chamber, air-dry 1 hour.
Wrap up in the same way at last and apply 6 layers of solution c.
Inner core was put into fume hood air-dry 48 hours.
(6) air-dry inner core is immersed in the distilled water, soaked 36 hours, liquid was changed once every 4～8 hours in the centre.Molten support holder and the porogen of going.
(7) support is taken out from distilled water, vacuum drying can obtain final support.
Final support sketch map as shown in Figure 2.Wherein the enlarged drawing of local A is as shown in Figure 3 among Fig. 2.Among Fig. 3, a is that porosity is 90%, the aperture about 70um the PLGA layer.B is the PCL-PET copolymeric material layer of atresia.C be the aperture about 120um, porosity is 75% PLGA layer.
Embodiment 2
Preparation has the three-dimensional block support of interior pipe network.This internal stent has the interior pipe network that is interconnected.Pipe network has three sheaf space bifurcation structures in this support, the level Four caliber, and its diameter is followed successively by 1200 μ m, 900 μ m, 600 μ m, 300 μ m.Interior tubular mesh shape as shown in Figure 3.This rack making flow process is as follows:
(1) according to the shape of interior pipe network, adopts pipe network inner core in the Solidworks software design.According to the support face shaping, design support outline inner core.And respectively the model that obtains is output as stl file.Interior pipe network core shape as shown in Figure 4
(2) based on the indirect interior pipe network inner core that is shaped of stereolithography technology.
Pipe network inner core in the laser stereolithography forming machine Auro-350 type uv equipment that at first uses Beijing Yin Hua laser fast forming and Tool and Die Technology company limited to produce is shaped.Moulding material is DSM Somos WaterShedTM 11120 photosensitive resins.Utilize the interior pipe network holder of shaping resin to make core, turn over the system silica gel mould.Fused maltose material is poured in the silica gel mould, and cooling back die sinking obtains pipe network inner core in the water solublity.
(3) based on the outline inner core direct forming that melt extrudes technology.
The MEM250-II type melted extrusion forming system that uses Beijing Yin Hua laser fast forming and Tool and Die Technology company limited to produce makes support outline holder.Moulding material is the mixture of maltose, glucose and sucrose.The main technologic parameters that adopts is: bed thickness 0.20mm, scanning speed 23mm/s.
Interior pipe network holder and outline holder are assembled, obtain support negative norm tool.
(3) with 3g PLGA (M
η: 100,000) be dissolved in 20ml one, four dioxane, be mixed with the polymer solution of 15% (wt/v).
(4) solution-cast of preparation in the step (3) is gone in the support negative norm tool of step (2) preparation, and mould put into-30 ℃ refrigerator and cooled and froze 4 hours.
(5) mould is put into freezer dryer, lyophilization 48 hours.
(6) support after the lyophilization is put into distilled water and soaked 24 hours, changed liquid once every 4～8 hours therebetween.
(7), can obtain having the support of specific interior pipe network and outline with support vacuum drying or natural air drying.
Embodiment 3
Preparation has the common bile duct support of plane bifurcation structure.This support macrostructure is that an internal diameter is the house steward of 9mm, tells the bifurcated that two internal diameters of face are respectively 8mm and 6mm.Tube wall requires the pore-free structure, and the stent forming material is PLLGA.
(1) design support inner core.Use the three dimensional structure of SolidWorks three-dimensional CAD software design inner core, and the cad model of support inner core is output as the stl file form.
(2) based on the inner core direct forming that melt extrudes technology.
The MEM250-II type melted extrusion forming system that uses Beijing Yin Hua laser fast forming and Tool and Die Technology company limited to produce makes support outline holder.Moulding material is the mixture of maltose, glucose and sucrose.The main technologic parameters that adopts is: bed thickness 0.20mm, scanning speed 23mm/s.
(3) 1g PLL6A (Mv:1000) is dissolved in the 50ml chloroform, is mixed with the polymer solution of 2% (wt/v).
(4) solution is poured into (C-MART board, W-71 type) in the air atomization spray gun, material evenly is sprayed on core surface.During spraying, inner core is placed in the square glass frame that three side sealing closes, the temperature in the instrument bezel is controlled at about 45 ℃.During spraying, inner core rotates around house steward's axis with 5-10 rev/min speed.The used compressed air of spray gun is provided by the plastics trachea by air compressor.Before the plastics trachea inserts spray gun, through 60 ℃ of water baths with the heating tube compressed air.Inner core is 8cm apart from the spray tip distance during spraying.Every spraying 30 seconds minutes paused 1 minute.Spray repeatedly 5 times.
(5) after spraying finishes, the inner core taking-up was put into the fume hood natural air drying 24 hours.Put into distilled water then and soaked 36 hours, changed liquid once every 4～8 hours therebetween.
(7) with support vacuum drying or natural air drying, get final product the common bile duct support.
Claims (5)
1, a kind of tissue engineering complex grid shape stent forming method based on soluble core technique is characterized in that this method carries out as follows:
A), at first according to the spatial form and the support inner flow passage spatial form of support outline, utilize three-dimensional graphics software, the three-dimensional electronic model of design inner core or mould;
B), adopt inanimate object toxicity, water-soluble thermoplastic, utilize Rapid Prototyping technique, direct forming or indirectly forming step a) in the inner core or the mould of design;
C), the selected at least a examples of natural biocompatible materials that dissolves in the biocompatible polymer material of volatile organic solvent or be insoluble to neutral aqueous solution, with volatilizable solvent the biocompatible materials of selecting being mixed with mass volume ratio concentration respectively is 2%～20% serial solution;
D), in the serial solution that step (c) is prepared, add porogen, biocompatible materials and porogen material are that 1: 0～100 ratio adds by weight, and with the solution mix homogeneously; Porogen adopts the mixture of sodium chloride particle, ammonium bicarbonate granule, water solublity monosaccharide or disaccharidase solid particle or above-mentioned several porogen.
E), adopt the process of spraying, infiltration, casting or electrospinning silk to uniformly spray, wrap up in the serial solution for preparing in the step d) on the interior core outer surface that applies formed thereby in step b) in order; Perhaps serial solution is poured in the dies cavity; And by dry naturally, vacuum drying or cryodesiccated method make its solvent evaporates;
F), inner core or the mould that obtains in the step e) immersed in the distilled water molten inner core and the porogen of removing; After support taken out, adopt that nature dries from distilled water, vacuum drying or cryodesiccated method vapor away the moisture in the support, promptly make grid shape stent or have the used in tissue engineering support of specific inner flow passage.
2. according to the described preparation method of claim 1, it is characterized in that: the inanimate object toxicity described in the step b), water-soluble thermoplastic adopt monosaccharide, disaccharidase, water soluble polysaccharide or its mixture.
3. according to the described preparation method of claim 1, it is characterized in that: the biocompatible polymer material that dissolves in volatile organic solvent described in the step c) adopts polylactic acid and polymer, poly-Acetic acid, hydroxy-, bimol. cyclic ester, polylactic acid-poly-glycolide copolymer, polycaprolactone, poly-beta-hydroxy-butanoic acid ester, gathers beta-hydroxy-butanoic acid ester-poly-hydroxyl pentanoate copolymer, polycaprolactone-polyethylene glycol segmented copolymer or polyurethane; The described examples of natural biocompatible materials that is insoluble to neutral aqueous solution adopts collagen.Described volatilizable organic solvent adopts a kind of or wherein several mixed system in halogenated hydrocarbons, ethyl acetate, one or four dioxane, dioxane, oxolane, chloroform or the dichloromethane.
4. according to claim 1,2 or 3 described preparation methoies, it is characterized in that: the powder that adds TCP or HA in the solution that can in step c), be prepared.
5. according to the described preparation method of claim 1, it is characterized in that: the direct forming method of inner core of support described in the step b) or mould, adopt melted extrusion forming technology, selective laser sintering or three-dimensional printing-forming; Described indirect forming technique process is as follows: at first adopt the prototype parts of making based on Rapid Prototyping technique, turn over system silica gel mould, utilize silica gel mould to make inner core or mould then; Or directly use rapid prototyping technology to make master mold, use master mold to make inner core or mould then.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100112281A CN100490762C (en) | 2005-01-21 | 2005-01-21 | Tissue engineering complex grid shape stent forming method base on core dissolving technology |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100112281A CN100490762C (en) | 2005-01-21 | 2005-01-21 | Tissue engineering complex grid shape stent forming method base on core dissolving technology |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1654028A true CN1654028A (en) | 2005-08-17 |
| CN100490762C CN100490762C (en) | 2009-05-27 |
Family
ID=34894171
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100112281A Expired - Fee Related CN100490762C (en) | 2005-01-21 | 2005-01-21 | Tissue engineering complex grid shape stent forming method base on core dissolving technology |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100490762C (en) |
Cited By (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100457187C (en) * | 2006-11-10 | 2009-02-04 | 中国人民解放军第二军医大学 | VEGF slowly releasing injection microsphere support and its prepn and use |
| CN101693123B (en) * | 2009-09-29 | 2012-07-25 | 同济大学 | Method for constructing composite structure tissue engineering bracket containing different extracellular matrixes |
| CN103341989A (en) * | 2013-07-08 | 2013-10-09 | 上海大学 | Regeneration bone scaffold forming system and method based on comprehensive 3D printing formation |
| CN104382670A (en) * | 2014-12-08 | 2015-03-04 | 西安交通大学 | Bionic construction method of artificial organics |
| CN104383606A (en) * | 2014-10-27 | 2015-03-04 | 北京航空航天大学 | High-strength high-elasticity intravascular stent and preparation method thereof |
| CN105031725A (en) * | 2015-07-13 | 2015-11-11 | 上海市第六人民医院 | Method for constructing segmental personalized human urethral three-dimensional stent material |
| CN105216316A (en) * | 2015-10-14 | 2016-01-06 | 上海大学 | A kind of combined forming process of multiple dimensioned passage |
| CN105310794A (en) * | 2015-02-14 | 2016-02-10 | 李贵才 | Method for preparing porous artificial nerve conduit with orientation structures on inner walls |
| CN105435314A (en) * | 2015-12-14 | 2016-03-30 | 李雷 | Preparation method of covered endovascular stent-graft |
| CN105616043A (en) * | 2016-03-18 | 2016-06-01 | 常州大学 | 3D printing and injection molding based silicone individualized airway stent preparation technology |
| CN106264781A (en) * | 2015-06-25 | 2017-01-04 | 李雷 | The manufacture method of overlay film frame, system |
| CN106581748A (en) * | 2016-12-09 | 2017-04-26 | 东华大学 | Production method of three-dimensional structured poly(glycerol-sebacate)-based macro-porous scaffold |
| CN106710416A (en) * | 2015-07-30 | 2017-05-24 | 上海微创医疗器械（集团）有限公司 | Vessel model, making method thereof, and device for making vessel model |
| CN106710406A (en) * | 2015-07-21 | 2017-05-24 | 上海微创医疗器械（集团）有限公司 | Vascular model and manufacturing method thereof, and spraying equipment |
| CN106710407A (en) * | 2015-07-30 | 2017-05-24 | 上海微创医疗器械（集团）有限公司 | Blood vessel model, manufacturing method thereof, and device for making blood vessel model |
| CN107049485A (en) * | 2017-03-29 | 2017-08-18 | 广州迈普再生医学科技有限公司 | The preparation method and tissue model of a kind of tissue model with cavity structure |
| CN107283594A (en) * | 2017-06-27 | 2017-10-24 | 闽江学院 | A kind of method that utilization 3D printing makes bodiless lacquer |
| CN107296669A (en) * | 2017-05-18 | 2017-10-27 | 西安交通大学 | A kind of outer suspension holdfast of degradable tracheae and its indirect 3D printing method |
| CN108452373A (en) * | 2017-06-21 | 2018-08-28 | 三的部落（上海）科技股份有限公司 | 3D printing biological support and its preparation method and application with gene slow releasing function |
| CN109701092A (en) * | 2019-01-29 | 2019-05-03 | 西安交通大学医学院第一附属医院 | The medical biliary tract rack material of degradable (the P3/4HB-PCL)-PU of one kind and preparation method |
| CN110115648A (en) * | 2019-05-15 | 2019-08-13 | 四川兴泰普乐医疗科技有限公司 | A kind of preparation method of 3D printing degradable blood vessel bracket |
| CN110859995A (en) * | 2019-11-14 | 2020-03-06 | 浙江大学 | Drug sustained-release coating based on double-layer heterogeneous structure and preparation method and application thereof |
| CN111148483A (en) * | 2017-07-28 | 2020-05-12 | 斯特拉塔西斯公司 | Method and system for manufacturing an object with vascular properties |
| CN111265715A (en) * | 2020-01-21 | 2020-06-12 | 上海交通大学 | Tissue engineering tubular organ preparation method |
| CN113144286A (en) * | 2021-04-21 | 2021-07-23 | 四川大学华西医院 | Degradable self-supporting artificial bile duct and preparation method thereof |
| US11549012B2 (en) | 2017-07-28 | 2023-01-10 | Stratasys Ltd. | Formulations usable in additive manufacturing of a three-dimensional object made of a soft material |
| US11559936B2 (en) | 2017-07-28 | 2023-01-24 | Stratasys Ltd. | Additive manufacturing processes employing a material featuring properties of a soft bodily tissue |
| US11696832B2 (en) | 2017-07-28 | 2023-07-11 | Stratasys Ltd. | Method and system for fabricating object featuring properties of a hard tissue |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3797010A4 (en) * | 2018-05-21 | 2022-03-16 | The University Of Sydney | A method of fabricating a casting |
-
2005
- 2005-01-21 CN CNB2005100112281A patent/CN100490762C/en not_active Expired - Fee Related
Cited By (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100457187C (en) * | 2006-11-10 | 2009-02-04 | 中国人民解放军第二军医大学 | VEGF slowly releasing injection microsphere support and its prepn and use |
| CN101693123B (en) * | 2009-09-29 | 2012-07-25 | 同济大学 | Method for constructing composite structure tissue engineering bracket containing different extracellular matrixes |
| CN103341989B (en) * | 2013-07-08 | 2015-07-29 | 上海大学 | The comprehensive Regenerated Bone stent forming System and method for be shaped is printed based on 3D |
| CN103341989A (en) * | 2013-07-08 | 2013-10-09 | 上海大学 | Regeneration bone scaffold forming system and method based on comprehensive 3D printing formation |
| CN104383606A (en) * | 2014-10-27 | 2015-03-04 | 北京航空航天大学 | High-strength high-elasticity intravascular stent and preparation method thereof |
| CN104382670B (en) * | 2014-12-08 | 2016-05-04 | 西安交通大学 | A kind of bionical construction method of artificial organs |
| CN104382670A (en) * | 2014-12-08 | 2015-03-04 | 西安交通大学 | Bionic construction method of artificial organics |
| CN105310794A (en) * | 2015-02-14 | 2016-02-10 | 李贵才 | Method for preparing porous artificial nerve conduit with orientation structures on inner walls |
| CN106264781A (en) * | 2015-06-25 | 2017-01-04 | 李雷 | The manufacture method of overlay film frame, system |
| CN105031725A (en) * | 2015-07-13 | 2015-11-11 | 上海市第六人民医院 | Method for constructing segmental personalized human urethral three-dimensional stent material |
| CN106710406A (en) * | 2015-07-21 | 2017-05-24 | 上海微创医疗器械（集团）有限公司 | Vascular model and manufacturing method thereof, and spraying equipment |
| CN106710416A (en) * | 2015-07-30 | 2017-05-24 | 上海微创医疗器械（集团）有限公司 | Vessel model, making method thereof, and device for making vessel model |
| CN106710407A (en) * | 2015-07-30 | 2017-05-24 | 上海微创医疗器械（集团）有限公司 | Blood vessel model, manufacturing method thereof, and device for making blood vessel model |
| CN105216316B (en) * | 2015-10-14 | 2017-10-24 | 上海大学 | A kind of combined forming process of multiple dimensioned passage |
| CN105216316A (en) * | 2015-10-14 | 2016-01-06 | 上海大学 | A kind of combined forming process of multiple dimensioned passage |
| CN105435314A (en) * | 2015-12-14 | 2016-03-30 | 李雷 | Preparation method of covered endovascular stent-graft |
| WO2017101583A1 (en) * | 2015-12-14 | 2017-06-22 | 李雷 | Method for preparing membrane-covered intravascular stent |
| CN105616043A (en) * | 2016-03-18 | 2016-06-01 | 常州大学 | 3D printing and injection molding based silicone individualized airway stent preparation technology |
| CN106581748B (en) * | 2016-12-09 | 2019-06-04 | 东华大学 | A kind of preparation method of three-dimensional structure sebacic acid and propyl tri-alcohol ester sill macropore bracket |
| CN106581748A (en) * | 2016-12-09 | 2017-04-26 | 东华大学 | Production method of three-dimensional structured poly(glycerol-sebacate)-based macro-porous scaffold |
| CN107049485A (en) * | 2017-03-29 | 2017-08-18 | 广州迈普再生医学科技有限公司 | The preparation method and tissue model of a kind of tissue model with cavity structure |
| CN107049485B (en) * | 2017-03-29 | 2021-09-17 | 广州迈普再生医学科技股份有限公司 | Preparation method of tissue model with cavity structure and tissue model |
| CN107296669A (en) * | 2017-05-18 | 2017-10-27 | 西安交通大学 | A kind of outer suspension holdfast of degradable tracheae and its indirect 3D printing method |
| CN108452373B (en) * | 2017-06-21 | 2021-06-01 | 三的部落（上海）科技股份有限公司 | 3D printing biological scaffold with gene slow release effect and preparation method and application thereof |
| CN108452373A (en) * | 2017-06-21 | 2018-08-28 | 三的部落（上海）科技股份有限公司 | 3D printing biological support and its preparation method and application with gene slow releasing function |
| CN107283594A (en) * | 2017-06-27 | 2017-10-24 | 闽江学院 | A kind of method that utilization 3D printing makes bodiless lacquer |
| US11549012B2 (en) | 2017-07-28 | 2023-01-10 | Stratasys Ltd. | Formulations usable in additive manufacturing of a three-dimensional object made of a soft material |
| CN111148483B (en) * | 2017-07-28 | 2022-11-15 | 斯特拉塔西斯公司 | Method and system for manufacturing an object with vascular properties |
| US11939468B2 (en) | 2017-07-28 | 2024-03-26 | Stratasys Ltd. | Formulations usable in additive manufacturing of a three-dimensional object made of a soft material |
| US11801630B2 (en) | 2017-07-28 | 2023-10-31 | Stratasys Ltd. | Method and system for fabricating object featuring properties of a blood vessel |
| US11696832B2 (en) | 2017-07-28 | 2023-07-11 | Stratasys Ltd. | Method and system for fabricating object featuring properties of a hard tissue |
| US11559936B2 (en) | 2017-07-28 | 2023-01-24 | Stratasys Ltd. | Additive manufacturing processes employing a material featuring properties of a soft bodily tissue |
| CN111148483A (en) * | 2017-07-28 | 2020-05-12 | 斯特拉塔西斯公司 | Method and system for manufacturing an object with vascular properties |
| CN109701092A (en) * | 2019-01-29 | 2019-05-03 | 西安交通大学医学院第一附属医院 | The medical biliary tract rack material of degradable (the P3/4HB-PCL)-PU of one kind and preparation method |
| CN109701092B (en) * | 2019-01-29 | 2021-11-09 | 西安交通大学医学院第一附属医院 | Degradable (P3/4HB-PCL) -PU medical biliary tract stent material and preparation method thereof |
| CN110115648A (en) * | 2019-05-15 | 2019-08-13 | 四川兴泰普乐医疗科技有限公司 | A kind of preparation method of 3D printing degradable blood vessel bracket |
| CN110115648B (en) * | 2019-05-15 | 2021-01-22 | 四川兴泰普乐医疗科技有限公司 | Preparation method of degradable intravascular stent by 3D printing |
| CN110859995A (en) * | 2019-11-14 | 2020-03-06 | 浙江大学 | Drug sustained-release coating based on double-layer heterogeneous structure and preparation method and application thereof |
| CN111265715A (en) * | 2020-01-21 | 2020-06-12 | 上海交通大学 | Tissue engineering tubular organ preparation method |
| CN113144286B (en) * | 2021-04-21 | 2022-12-09 | 四川大学华西医院 | Degradable self-supporting artificial bile duct and preparation method thereof |
| CN113144286A (en) * | 2021-04-21 | 2021-07-23 | 四川大学华西医院 | Degradable self-supporting artificial bile duct and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100490762C (en) | 2009-05-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100490762C (en) | Tissue engineering complex grid shape stent forming method base on core dissolving technology | |
| CN107693846B (en) | A kind of bionical vascularization soft tissue and preparation method thereof with multilayer blood vessel structure | |
| Gao et al. | Fabrication of electrospun nanofibrous scaffolds with 3D controllable geometric shapes | |
| Zhu et al. | Biofabrication of tissue scaffolds | |
| Liu et al. | Multinozzle low‐temperature deposition system for construction of gradient tissue engineering scaffolds | |
| US20040258729A1 (en) | Tissue engineering scaffolds | |
| Zhang et al. | A review of preparation methods of porous skin tissue engineering scaffolds | |
| Seunarine et al. | 3D polymer scaffolds for tissue engineering | |
| Mobini et al. | Bioactivity and biocompatibility studies on silk-based scaffold for bone tissue engineering | |
| Koyyada et al. | Recent advancements and associated challenges of scaffold fabrication techniques in tissue engineering applications | |
| CN107137775B (en) | Preparation method of thermosetting elastomer tissue engineering scaffold with multistage pore structure | |
| KR101019186B1 (en) | Method for preparing 3-dimensional porous polymer scaffold | |
| CN107308502A (en) | 3D printing support of composite load growth factor microballoon and preparation method thereof | |
| CN105457101A (en) | Preparation method of small-caliber intravascular stent of three-layer structure | |
| KR102316548B1 (en) | Two-step phase separation-based 3D bioplotting for macro/nanoporous collagen scaffolds comprised of nanofibrous collagen filaments | |
| Li et al. | Current status of additive manufacturing for tissue engineering scaffold | |
| KR101387159B1 (en) | Making method for dual-pore scaffold and the scaffold | |
| CA2962927A1 (en) | Nanofiber structures and methods of synthesis and use thereof | |
| Tan et al. | Design and fabrication of a non-clogging scaffold composed of semi-permeable membrane | |
| CN103143062A (en) | Three-dimensional controllable incremental forming method and forming system for active osteochondral integrated gradient scaffold | |
| CN112743850B (en) | Preparation method of low-temperature biological 3D printing composite stent | |
| Allaf | Melt-molding technologies for 3D scaffold engineering | |
| CN113244460A (en) | Oriented microchannel bracket for promoting tissue regeneration and preparation method thereof | |
| Safinsha et al. | Composite scaffolds in tissue engineering | |
| CN103171153A (en) | Process method for pneumatically extruding, depositing and molding porous biological bone scaffold |
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: 20090527 Termination date: 20130121 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |