CN111995793A - Material for low-temperature 3D printing of porous polycaprolactone scaffold and printing method - Google Patents
Material for low-temperature 3D printing of porous polycaprolactone scaffold and printing method Download PDFInfo
- Publication number
- CN111995793A CN111995793A CN201910735130.2A CN201910735130A CN111995793A CN 111995793 A CN111995793 A CN 111995793A CN 201910735130 A CN201910735130 A CN 201910735130A CN 111995793 A CN111995793 A CN 111995793A
- Authority
- CN
- China
- Prior art keywords
- printing
- polycaprolactone
- solvent
- scaffold
- pore
- 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.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/26—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/10—Processes of additive manufacturing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
- B29C64/30—Auxiliary operations or equipment
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y10/00—Processes of additive manufacturing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y40/00—Auxiliary operations or equipment, e.g. for material handling
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y70/00—Materials specially adapted for additive manufacturing
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2201/00—Foams characterised by the foaming process
- C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
- C08J2201/044—Elimination of an inorganic solid phase
- C08J2201/0444—Salts
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
- C08J2367/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones
Landscapes
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Health & Medical Sciences (AREA)
- Manufacturing & Machinery (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Mechanical Engineering (AREA)
- Optics & Photonics (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention provides a material for low-temperature 3D printing of a porous polycaprolactone scaffold, which is prepared from the following raw materials in percentage by weight: 4-32% of polycaprolactone, 8-32% of pore-foaming agent and 60-80% of solvent; the porogenic agent is inorganic compound particles with the solubility higher than 10g/L in water and the solubility lower than 0.01g/L in an organic solvent; the solvent is an organic solvent in which the solubility of polycaprolactone is higher than 10 g/L. The 3D printing material provided by the invention can realize low-temperature 3D printing below 37 ℃, avoids the destruction of the polycaprolactone molecular structure caused by high-temperature printing, also avoids the destruction of the mechanical property of the polycaprolactone support, and is suitable for printing high-molecular-weight polycaprolactone. Meanwhile, the solvent and the pore-forming agent can be removed by a simple method, and the PCL porous scaffold with the set porosity is finally obtained, the microporous structure of the PCL porous scaffold is more favorable for the adhesion and infiltration growth of cells, the problems in the prior art are overcome, and the PCL porous scaffold has a very good application prospect.
Description
Technical Field
The invention relates to a printing material and a printing method for low-temperature 3D printing of a porous polycaprolactone support.
Background
The 3D printing technology, one of the rapid prototyping technologies, is a technology for constructing a three-dimensional object by stacking and bonding special materials such as metal powder, ceramic powder, plastic, biological tissue and the like layer by layer in a laser beam, hot melt nozzle and other modes through a computer software layering dispersion and numerical control forming system and finally stacking and forming by taking a computer three-dimensional design as a blueprint. The biological 3D technology is based on a computer three-dimensional model, and is a 3D printing technology for printing biological three-dimensional structures, in-vitro three-dimensional biological function bodies, regenerative medicine models and other biomedical products with complex structures and functions by an additive manufacturing method according to requirements of bionic forms, biological functions, cell specific micro-environments and the like of biological materials or cells through a dispersion-accumulation method.
Polycaprolactone (PCL) is a thermoplastic semi-crystalline polyester obtained by ring-opening polymerization of caprolactone using a diol as an initiator. The PCL has a melting point of 60 ℃, a glass transition temperature of-60 ℃, a decomposition temperature of 200 ℃, and a structural repeating unit of the PCL is provided with 5 nonpolar methylene groups and a polar ester group. PCL has good biocompatibility and can be completely biodegraded into water and carbon dioxide, so that the PCL can be widely applied to the field of biological materials and can be used as a drug sustained-release material and a tissue engineering scaffold. PCL has excellent toughness, a lower melting temperature and good thermal stability, and is therefore also an excellent 3D printing material. However, PCL has a low melting temperature, but it has a high viscosity at the melting temperature, requires a high extrusion pressure, is difficult to print, and has high requirements for printing equipment. Currently, PCL 3D printing is mainly performed at high temperatures, which typically are above 100 ℃ and even close to 200 ℃ decomposition temperature of PCL. The invention patent (with the patent number of CN201610676960.9) of 'a method for preparing a vascular wall stent by using a 3D printing technology and a preparation thereof' proposed by Zhou Wuyi and Huyang, etc. of south China agricultural university introduces a printing method of the vascular wall stent, wherein the polymer used for printing is a high-temperature molten high-molecular material, and the printing temperature is as high as 180 ℃. The phenomenon that the material is easy to yellow and degrade in the printing process is caused, the molecular structure of the PCL is damaged, and the performance of the printed bracket is influenced.
The existing low-temperature 3D PCL printing method is to select a lower molecular weight PCL polymer for printing at a relatively low temperature. The invention patent of 'a 3D printing process method of polycaprolactone low-temperature material and printing equipment thereof' (application number is CN 103980682B) by Nie Jiang, Chengan Tan et al, south China agricultural university, discloses a method for 3D printing of PCL at 85 ℃. The principle is that the PCL with lower molecular weight (weight average molecular weight is 3-8 ten thousand) can be molten at 85 ℃ for fused deposition molding. However, since PCL polymers with a molecular weight higher than 8 ten thousand cannot be melted at 85 ℃, this method is not suitable for 3D printing of PCL polymers with a molecular weight higher than 8 ten thousand.
Patent CN106178132A discloses a method for low-temperature 3D printing of polycaprolactone: mixing the mixed material of the bioactive glass powder and the calcium phosphate with a polyethylene lactone/dichloromethane solution, and performing low-temperature 3D printing to obtain the composite bone cement scaffold. However, the printing performance is improved by adding the mixed material of the bioactive glass powder and the calcium phosphate, and the prepared polycaprolactone bracket is difficult to obtain a micro-pore structure and is not beneficial to cell growth.
These problems described above limit the application of PCL in the field of biological 3D printing.
Disclosure of Invention
In order to solve the problems, the invention provides a material for low-temperature 3D printing of a porous polycaprolactone scaffold and a printing method.
The invention provides a material for low-temperature 3D printing of a porous polycaprolactone scaffold, which is prepared from the following raw materials in percentage by weight: 4-32% of polycaprolactone, 8-32% of pore-foaming agent and 60-80% of solvent;
the porogenic agent is inorganic compound particles with the solubility higher than 10g/L in water and the solubility lower than 0.01g/L in an organic solvent;
the solvent is an organic solvent in which the solubility of polycaprolactone is higher than 10 g/L.
Further, the material is composed of the following raw materials in percentage by weight: 10-20% of polycaprolactone, 10-20% of a pore-foaming agent and 70% of a solvent.
Further, the material is composed of the following raw materials in percentage by weight: 12% of polycaprolactone, 18% of pore-foaming agent and 70% of solvent.
Further, the pore-foaming agent is one or more of sodium chloride, calcium chloride, potassium chloride, copper chloride, sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, sodium sulfate, potassium sulfate and copper sulfate;
the solvent is one or more of chloroform, dichloromethane and tetrahydrofuran;
the molecular weight of the polycaprolactone is 3-30 ten thousand.
Further, the pore-foaming agent is sodium chloride, sodium bicarbonate or potassium sulfate;
the solvent is chloroform or tetrahydrofuran;
the molecular weight of the polycaprolactone is 10-15 ten thousand;
preferably, the first and second electrodes are formed of a metal,
the pore-foaming agent is potassium sulfate;
the solvent is chloroform;
the molecular weight of the polycaprolactone was 15 ten thousand.
Further, the particle size of the pore-foaming agent is less than 40 μm.
Further, the material is prepared by completely dissolving polycaprolactone in a solvent, adding a pore-forming agent, and uniformly mixing to obtain a printing material mixture; dispersing the printing material mixture in ultrasonic waves, then continuing stirring, and finally, performing ultrasonic dispersion again to obtain the printing material mixture;
preferably, the material is a printing material mixture obtained by completely dissolving polycaprolactone in a solvent, adding a pore-forming agent and uniformly mixing; and then, dispersing the printing material mixture in 40KHz ultrasonic waves for 5 minutes, taking out and stirring for 30 minutes, and finally, dispersing in 40KHz ultrasonic waves for 5 minutes again to obtain the printing material.
The invention also provides a method for low-temperature 3D printing of the porous polycaprolactone scaffold by using the material for low-temperature 3D printing of the porous polycaprolactone scaffold, which comprises the following steps:
(1) carrying out model design on the support to be printed by using software;
(2) setting printing parameters;
(3) printing the materials to obtain a support;
(4) and after printing, placing the printed bracket in a fume hood for 12 hours, then soaking the printed bracket in deionized water, removing a pore-forming agent and a residual solvent, and finally freeze-drying to obtain the porous carbon nano tube.
Further, the air conditioner is provided with a fan,
in the step (4), the weight-to-volume ratio of the bracket to the deionized water is 1:1000 (g: mL);
and/or, in step (4), the freeze-drying is pre-freezing at-20 ℃ overnight and then freeze-drying at-80 ℃ for 24 hours.
The invention also provides a porous polycaprolactone scaffold, which is prepared by 3D printing the material for low-temperature 3D printing of the porous polycaprolactone scaffold according to the method.
The invention also provides application of the material for low-temperature 3D printing of the porous polycaprolactone scaffold in preparation of non-bone hard tissue and soft tissue repair materials.
In the invention, the room temperature is 25 +/-5 ℃, and the overnight time is 12 +/-2 h.
The material for low-temperature 3D printing of the porous polycaprolactone stent is not only suitable for the biological 3D printer (Envision Tec, Germany) in the embodiment of the invention, but also suitable for other biological 3D printers for extrusion printing (mainly comprising printing methods such as pneumatic, piston and spiral extrusion). When other biological 3D printers are adopted, corresponding structural design software can be selected according to specific printing requirements for designing a printing model, a support model file with a corresponding format and capable of being identified is output, and printing parameters are set according to actual conditions.
The invention provides a material for low-temperature 3D printing of a porous polycaprolactone scaffold, which is prepared by dissolving polycaprolactone in a solvent and mixing the dissolved polycaprolactone with a pore-forming agent sodium chloride, can realize low-temperature 3D printing below 37 ℃, avoids the destruction of a polycaprolactone molecular structure caused by high-temperature printing, also avoids the destruction of the mechanical property of the polycaprolactone scaffold, and is suitable for printing of high-molecular-weight polycaprolactone. Meanwhile, the solvent and the pore-forming agent can be removed by a simple method, and the PCL porous scaffold with the set porosity is finally obtained, the microporous structure of the PCL porous scaffold is more favorable for the adhesion and infiltration growth of cells, the problems in the prior art are overcome, and the PCL porous scaffold has a very good application prospect.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
FIG. 1 is a surface topography inspection (SEM) of a porous polycaprolactone scaffold obtained by low temperature 3D printing according to the present invention. A. Example 1; B. example 2; C. example 3; D. example 4; E. example 5.
FIG. 2 shows the adhesion growth of cells on the surface of PCL porous scaffold. A. Example 1 scaffold (porosity 20%); B. example 4 scaffolds (porosity 80%).
Detailed Description
The starting materials and equipment used in the embodiment of the present invention are known products and obtained by purchasing commercially available products unless otherwise specified. The printer of the present invention: 3D Bioplotter (Envision Tec, Germany).
Example 1 the invention relates to a low-temperature 3D printing porous polycaprolactone stent
1. Weight percent of printing material
32 percent of Polycaprolactone (PCL) with the molecular weight of 3 ten thousand, 60 percent of tetrahydrofuran solvent and 8 percent of sodium chloride serving as pore-foaming agent.
2. Printing method
(1) Model design: and (3) carrying out model design by using Creo software, setting the length of the bracket to be 60.0mm, the width to be 6.0mm and the height to be 1.0mm, and outputting the designed bracket model in stl format.
(2) Software processing: and processing the stl file output by the Creo software by using Magic software, and checking whether the model has defects or loopholes during design. And setting the number of printing layers to be 3 and the layer thickness to be 325 mu m, and outputting the model to be an stl file capable of identifying workstation software for a 3D printer after the processing is finished.
(3) Preparation of printing material: dissolving 32 wt% of polycaprolactone (molecular weight of 3 ten thousand) in 60 wt% of tetrahydrofuran, adding 8 wt% of sodium chloride, ultrasonically treating the mixed material for 5 minutes, then stirring for 30 minutes at 37 ℃, and ultrasonically treating again for 5 minutes after completion. And transferring the printing paste into a printing material barrel, centrifuging at 2000r/min for 10s to remove bubbles at the lower layer of the printing paste, sealing and placing in a refrigerator at 4 ℃ for later use.
(4) Printing: and after checking whether the software of the 3D printer and the printer computer workstation normally runs, loading the stl software generated by the processing of the Magic software by using the computer workstation. The diameter of the printing nozzle is selected to be 400 mu m, the printing gap is set to be 750 mu m, the printing temperature is set to be 37 ℃, the temperature of the carrying platform is set to be 20 ℃, the printing pressure is set to be 3.0bar, the printing speed is set to be 5mm/s, and the printing is started.
(5) Processing of the printed bracket: after the PCL scaffold was printed, the scaffold was moved into a fume hood to air dry overnight, and then the scaffold was dried in a weight to volume ratio of 1: soaking the PCL scaffold into deionized water at a ratio of 1000 (g: mL), replacing the deionized water every day, dissolving and removing sodium chloride in the scaffold, completely removing NaCl after soaking for 5 days, taking out the PCL scaffold after completely removing NaCl, pre-freezing at-20 ℃ overnight, and freeze-drying at-80 ℃ for 12 hours to remove water in the scaffold.
Embodiment 2, the low-temperature 3D printing porous polycaprolactone stent
1. Weight percent of printing material
18 percent of Polycaprolactone (PCL) with the molecular weight of 10 ten thousand, 70 percent of tetrahydrofuran solvent and 12 percent of sodium bicarbonate serving as a pore-foaming agent.
2. Printing method
(1) Model design: and (3) carrying out model design by using Creo software, setting the length of the bracket to be 60.0mm, the width to be 6.0mm and the height to be 1.0mm, and outputting the designed bracket model in stl format.
(2) Software processing: and processing the stl file output by the Creo software by using Magic software, and checking whether the model has defects or loopholes during design. And setting the number of printing layers to be 3 and the layer thickness to be 325 mu m, and outputting the model to be an stl file capable of identifying workstation software for a 3D printer after the processing is finished.
(3) Preparation of printing material: dissolving 18 wt% of polycaprolactone (molecular weight 10 ten thousand) in 70 wt% of tetrahydrofuran, adding 12 wt% of sodium bicarbonate, sonicating the mixture for 5 minutes, then stirring at 37 ℃ for 30 minutes, and again sonicating for 5 minutes after completion. And transferring the printing paste into a printing material barrel, centrifuging at 2000r/min for 10s to remove bubbles at the lower layer of the printing paste, sealing and placing in a refrigerator at 4 ℃ for later use.
(4) Printing: and after checking whether the software of the 3D printer and the printer computer workstation normally runs, loading the stl software generated by the processing of the Magic software by using the computer workstation. The diameter of the printing nozzle is selected to be 400 mu m, the printing gap is set to be 750 mu m, the printing temperature is set to be 37 ℃, the temperature of the carrying platform is set to be 20 ℃, the printing pressure is set to be 2.0bar, the printing speed is set to be 5mm/s, and the printing is started.
(5) Processing of the printed bracket: after the PCL scaffold was printed, the scaffold was moved into a fume hood to air dry overnight, and then the scaffold was dried in a weight to volume ratio of 1: soaking the PCL stent in deionized water at a ratio of 1000 (g: mL) for 5 days, dissolving and removing sodium bicarbonate in the stent by replacing the deionized water every day, completely removing the sodium bicarbonate after soaking for 5 days, taking out the PCL stent after completely removing the sodium bicarbonate, pre-freezing the PCL stent at-20 ℃ overnight, and freeze-drying the PCL stent at-80 ℃ for 12 hours to remove water in the stent.
Embodiment 3, the low-temperature 3D printing porous polycaprolactone stent
1. Weight percent of printing material
12% of Polycaprolactone (PCL) with the molecular weight of 15 ten thousand, 70% of chloroform as a solvent and 18% of potassium sulfate as a pore-foaming agent.
2. Printing method
(1) Model design: and (3) carrying out model design by using Creo software, setting the length of the bracket to be 60.0mm, the width to be 6.0mm and the height to be 1.0mm, and outputting the designed bracket model in stl format.
(2) Software processing: and processing the stl file output by the Creo software by using Magic software, and checking whether the model has defects or loopholes during design. And setting the number of printing layers to be 3 and the layer thickness to be 325 mu m, and outputting the model to be an stl file capable of identifying workstation software for a 3D printer after the processing is finished.
(3) Preparation of printing material: dissolving 12% by weight of polycaprolactone (molecular weight 15 ten thousand) in 70% by weight of chloroform, adding 18% by weight of potassium sulfate, subjecting the mixture to ultrasound for 5 minutes, stirring at 37 ℃ for 30 minutes, and subjecting the mixture to ultrasound again for 5 minutes. And transferring the printing paste into a printing material barrel, centrifuging at 2000r/min for 10s to remove bubbles at the lower layer of the printing paste, sealing and placing in a refrigerator at 4 ℃ for later use.
(4) Printing: and after checking whether the software of the 3D printer and the printer computer workstation normally runs, loading the stl software generated by the processing of the Magic software by using the computer workstation. The diameter of the printing nozzle is selected to be 400 mu m, the printing gap is set to be 750 mu m, the printing temperature is set to be 37 ℃, the temperature of the carrying platform is set to be 20 ℃, the printing pressure is set to be 0.8bar, the printing speed is set to be 5mm/s, and the printing is started.
(5) Processing of the printed bracket: after the PCL scaffold was printed, the scaffold was moved into a fume hood to air dry overnight, and then the scaffold was dried in a weight to volume ratio of 1: soaking the PCL bracket into deionized water at a ratio of 1000 (g: mL), replacing the deionized water every day, dissolving and removing potassium sulfate in the bracket, completely removing the potassium sulfate after soaking for 5 days, taking out the PCL bracket after completely removing the potassium sulfate, pre-freezing at-20 ℃ overnight, freeze-drying at-80 ℃ for 12 hours, and removing water in the bracket.
Example 4 Low temperature 3D printing porous polycaprolactone scaffold
1. Weight percent of printing material
4 percent of Polycaprolactone (PCL) with molecular weight of 30 ten thousand, 80 percent of solvent chloroform and 16 percent of pore-foaming agent sodium chloride.
2. Printing method
(1) Model design: and (3) carrying out model design by using Creo software, setting the length of the bracket to be 60.0mm, the width to be 6.0mm and the height to be 1.0mm, and outputting the designed bracket model in stl format.
(2) Software processing: and processing the stl file output by the Creo software by using Magic software, and checking whether the model has defects or loopholes during design. And setting the number of printing layers to be 3 and the layer thickness to be 325 mu m, and outputting the model to be an stl file capable of identifying workstation software for a 3D printer after the processing is finished.
(3) Preparation of printing material: dissolving 4 wt% of polycaprolactone (molecular weight 30 ten thousand) in 80 wt% of chloroform, adding 16 wt% of sodium chloride, subjecting the mixture to ultrasound for 5 minutes, stirring at 37 ℃ for 30 minutes, and subjecting the mixture to ultrasound again for 5 minutes. And transferring the printing paste into a printing material barrel, centrifuging at 2000r/min for 10s to remove bubbles at the lower layer of the printing paste, sealing and placing in a refrigerator at 4 ℃ for later use.
(4) Printing: and after checking whether the software of the 3D printer and the printer computer workstation normally runs, loading the stl software generated by the processing of the Magic software by using the computer workstation. The diameter of the printing nozzle is selected to be 400 mu m, the printing gap is set to be 750 mu m, the printing temperature is set to be 37 ℃, the temperature of the carrying platform is set to be 20 ℃, the printing pressure is set to be 0.8bar, the printing speed is set to be 5mm/s, and the printing is started.
(5) Processing of the printed bracket: after the PCL scaffold was printed, the scaffold was moved into a fume hood to air dry overnight, and then the scaffold was dried in a weight to volume ratio of 1: soaking the PCL scaffold into deionized water at a ratio of 1000 (g: mL), replacing the deionized water every day, dissolving and removing sodium chloride in the scaffold, completely removing NaCl after soaking for 5 days, taking out the PCL scaffold after completely removing NaCl, pre-freezing at-20 ℃ overnight, and freeze-drying at-80 ℃ for 12 hours to remove water in the scaffold.
Example 5 Low temperature 3D printing porous polycaprolactone Stent
1. Weight percent of printing material
8 percent of Polycaprolactone (PCL) with the molecular weight of 10 ten thousand, 60 percent of tetrahydrofuran solvent and 32 percent of sodium chloride serving as pore-foaming agent.
2. Printing method
(1) Model design: and (3) carrying out model design by using Creo software, setting the length of the bracket to be 60.0mm, the width to be 6.0mm and the height to be 1.0mm, and outputting the designed bracket model in stl format.
(2) Software processing: and processing the stl file output by the Creo software by using Magic software, and checking whether the model has defects or loopholes during design. And setting the number of printing layers to be 3 and the layer thickness to be 325 mu m, and outputting the model to be an stl file capable of identifying workstation software for a 3D printer after the processing is finished.
(3) Preparation of printing material: dissolving 8% by weight of polycaprolactone (molecular weight 10 ten thousand) in 60% by weight of tetrahydrofuran, adding 32% by weight of sodium chloride, subjecting the mixture to ultrasound for 5 minutes, stirring at 37 ℃ for 30 minutes, and subjecting the mixture to ultrasound again for 5 minutes. And transferring the printing paste into a printing material barrel, centrifuging at 2000r/min for 10s to remove bubbles at the lower layer of the printing paste, sealing and placing in a refrigerator at 4 ℃ for later use.
(4) Printing: and after checking whether the software of the 3D printer and the printer computer workstation normally runs, loading the stl software generated by the processing of the Magic software by using the computer workstation. The diameter of the printing nozzle is selected to be 400 mu m, the printing gap is set to be 750 mu m, the printing temperature is set to be 37 ℃, the temperature of the carrying platform is set to be 20 ℃, the printing pressure is set to be 0.8bar, the printing speed is set to be 5mm/s, and the printing is started.
(5) Processing of the printed bracket: after the PCL scaffold was printed, the scaffold was moved into a fume hood to air dry overnight, and then the scaffold was dried in a weight to volume ratio of 1: soaking the PCL scaffold into deionized water at a ratio of 1000 (g: mL), replacing the deionized water every day, dissolving and removing sodium chloride in the scaffold, completely removing NaCl after soaking for 5 days, taking out the PCL scaffold after completely removing NaCl, pre-freezing at-20 ℃ overnight, and freeze-drying at-80 ℃ for 12 hours to remove water in the scaffold.
The beneficial effects of the invention are verified by the following specific test examples:
test example 1 detection of porous polycaprolactone scaffold obtained by low-temperature 3D printing according to the invention
And (3) taking the porous polycaprolactone scaffold obtained by low-temperature 3D printing in the embodiment 1-5, and carrying out residual solvent content detection, surface morphology detection and porosity detection. The results are shown in table 1, table 2 and fig. 1.
And (3) residual solvent detection: the residual solvent content in the printing support is detected by using a headspace gas chromatography (HS-GC), and the residual solvent content in the support is required to be lower than 0.06 percent specified by pharmacopoeia.
Surface topography detection: and detecting the surface topography of the printing support by using a Scanning Electron Microscope (SEM).
And (3) detecting porosity: and detecting the porosity of the support obtained after printing by using a pycnometer method, wherein the porosity of the support obtained after printing is required to be not deviated from the set porosity by more than 5%.
Table 1 residual solvent content of porous polycaprolactone scaffolds obtained by low temperature 3D printing according to the invention
| Group of | Residual solvent content (%) |
| Example 1 | 4.6×10-5 |
| Example 2 | 5.4×10-5 |
| Example 3 | 3.4×10-5 |
| Example 4 | 8.1×10-5 |
| Example 5 | 6.3×10-5 |
TABLE 2 porosity of porous polycaprolactone scaffolds obtained by low temperature 3D printing according to the invention
| Group of | Porosity (%) | Setting porosity (%) | Deviation (%) |
| Example 1 | 19.22 | 20 | 3.9 |
| Example 2 | 39.21 | 40 | 1.98 |
| Example 3 | 61.12 | 60 | 1.87 |
| Example 4 | 82.32 | 80 | 2.9 |
| Example 5 | 81.85 | 80 | 2.31 |
The test result shows that: the content of residual solvent in the porous polycaprolactone scaffold obtained by low-temperature 3D printing is lower than 0.06 percent (table 1) specified by pharmacopoeia; and the porosity deviation of the porous polycaprolactone scaffold obtained by low-temperature 3D printing is 1.87-3.9% and less than 5% (table 2), and the specification error is small and meets the requirement. From table 2 and fig. 1, it can be further understood that the printing material of the present invention can be printed to obtain PCL porous scaffolds with different porosities and pore structures according to needs.
The PCL porous scaffolds prepared in example 1 (porosity 20%) and the PCL porous scaffolds prepared in example 4 (porosity 80%) were co-cultured with 3T3 mouse fibroblasts for 7 days, and then the growth of the cells was observed. The results are shown in FIG. 2. As shown in figure 2, the polycaprolactone scaffold prepared by the invention has a porous structure and a certain porosity, is beneficial to cell adhesion and growth, and meets the requirements of tissue engineering repair material scaffolds.
In conclusion, the invention provides a material for low-temperature 3D printing of a porous polycaprolactone scaffold, which is prepared by dissolving polycaprolactone in a solvent and then mixing the dissolved polycaprolactone with a pore-forming agent sodium chloride, and the material can realize low-temperature 3D printing below 37 ℃, avoid the destruction of the molecular structure of polycaprolactone caused by high-temperature printing, avoid the destruction of the mechanical property of the polycaprolactone scaffold, and is suitable for printing high-molecular-weight polycaprolactone. Meanwhile, the solvent and the pore-forming agent can be removed by a simple method, and the PCL porous scaffold with the set porosity is finally obtained, the microporous structure of the PCL porous scaffold is more favorable for the adhesion and infiltration growth of cells, the problems in the prior art are overcome, and the PCL porous scaffold has a very good application prospect.
Claims (11)
1. The utility model provides a material that is used for porous polycaprolactone support of low temperature 3D printing which characterized in that: the material consists of the following raw materials in percentage by weight: 4-32% of polycaprolactone, 8-32% of pore-foaming agent and 60-80% of solvent;
the porogenic agent is inorganic compound particles with the solubility higher than 10g/L in water and the solubility lower than 0.01g/L in an organic solvent;
the solvent is an organic solvent in which the solubility of polycaprolactone is higher than 10 g/L.
2. The material of claim 1, wherein: the material consists of the following raw materials in percentage by weight: 10-20% of polycaprolactone, 10-20% of a pore-foaming agent and 70% of a solvent.
3. The material of claim 2, wherein: the material consists of the following raw materials in percentage by weight: 12% of polycaprolactone, 18% of pore-foaming agent and 70% of solvent.
4. A material according to any one of claims 1 to 3, wherein: the pore-forming agent is one or more of sodium chloride, calcium chloride, potassium chloride, copper chloride, sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, sodium sulfate, potassium sulfate and copper sulfate;
the solvent is one or more of chloroform, dichloromethane and tetrahydrofuran;
the molecular weight of the polycaprolactone is 3-30 ten thousand.
5. The material of claim 4, wherein: the pore-foaming agent is sodium chloride, sodium bicarbonate or potassium sulfate;
the solvent is chloroform or tetrahydrofuran;
the molecular weight of the polycaprolactone is 10-15 ten thousand;
preferably, the first and second electrodes are formed of a metal,
the pore-foaming agent is potassium sulfate;
the solvent is chloroform;
the molecular weight of the polycaprolactone was 15 ten thousand.
6. A material according to any one of claims 1 to 3, wherein: the particle size of the pore-foaming agent is less than 40 μm.
7. A material according to any one of claims 1 to 3, wherein: the printing material is prepared by completely dissolving polycaprolactone in a solvent, adding a pore-foaming agent, and uniformly mixing to obtain a printing material mixture; dispersing the printing material mixture in ultrasonic waves, then continuing stirring, and finally, performing ultrasonic dispersion again to obtain the printing material mixture;
preferably, the material is a printing material mixture obtained by completely dissolving polycaprolactone in a solvent, adding a pore-forming agent and uniformly mixing; and then, dispersing the printing material mixture in 40KHz ultrasonic waves for 5 minutes, taking out and stirring for 30 minutes, and finally, dispersing in 40KHz ultrasonic waves for 5 minutes again to obtain the printing material.
8. A method for low-temperature 3D printing of a porous polycaprolactone scaffold by using the material for low-temperature 3D printing of the porous polycaprolactone scaffold as claimed in any one of claims 1 to 7, characterized in that: it comprises the following steps:
(1) carrying out model design on the support to be printed by using software;
(2) setting printing parameters;
(3) printing the material of any one of claims 1 to 7 to obtain a support;
(4) and after printing, placing the printed bracket in a fume hood for 12 hours, then soaking the printed bracket in deionized water, removing a pore-forming agent and a residual solvent, and finally freeze-drying to obtain the porous carbon nano tube.
9. The method of claim 8, wherein:
in the step (4), the weight-to-volume ratio of the bracket to the deionized water is 1:1000 (g: mL);
and/or, in step (4), the freeze-drying is pre-freezing at-20 ℃ overnight and then freeze-drying at-80 ℃ for 24 hours.
10. A porous polycaprolactone stent is characterized in that: the material for low-temperature 3D printing of the porous polycaprolactone scaffold is obtained by 3D printing of the material for low-temperature 3D printing of the porous polycaprolactone scaffold according to the method of claim 8 or 9.
11. Use of the porous polycaprolactone scaffold printed according to the method of claim 8 or 9 for low temperature 3D printing of the material of the porous polycaprolactone scaffold of any one of claims 1 to 7 for the preparation of non-osseous hard tissue, soft tissue repair material.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910735130.2A CN111995793A (en) | 2019-08-09 | 2019-08-09 | Material for low-temperature 3D printing of porous polycaprolactone scaffold and printing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910735130.2A CN111995793A (en) | 2019-08-09 | 2019-08-09 | Material for low-temperature 3D printing of porous polycaprolactone scaffold and printing method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111995793A true CN111995793A (en) | 2020-11-27 |
Family
ID=73461424
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910735130.2A Pending CN111995793A (en) | 2019-08-09 | 2019-08-09 | Material for low-temperature 3D printing of porous polycaprolactone scaffold and printing method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111995793A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112743850A (en) * | 2020-12-23 | 2021-05-04 | 华中科技大学鄂州工业技术研究院 | Preparation method of low-temperature biological 3D printing composite stent |
| CN112972765A (en) * | 2021-02-22 | 2021-06-18 | 苏州大学 | Silk fibroin 3D printing biological ink and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101264341A (en) * | 2008-04-11 | 2008-09-17 | 东华大学 | Three-dimensional porous tissue engineering bracket material, preparation and application thereof |
| CN102321352A (en) * | 2011-03-18 | 2012-01-18 | 华东理工大学 | Polycaprolactone in mesoporous structure and preparation method and application thereof |
| CN106668948A (en) * | 2017-03-01 | 2017-05-17 | 北京大学第三医院 | Tissue engineering stent based on low-temperature rapid modeling and preparation method thereof |
| CN107823715A (en) * | 2017-10-20 | 2018-03-23 | 昆明理工大学 | A kind of compound porous bone tissue engineering scaffolds of PCL/HA and preparation method thereof |
-
2019
- 2019-08-09 CN CN201910735130.2A patent/CN111995793A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101264341A (en) * | 2008-04-11 | 2008-09-17 | 东华大学 | Three-dimensional porous tissue engineering bracket material, preparation and application thereof |
| CN102321352A (en) * | 2011-03-18 | 2012-01-18 | 华东理工大学 | Polycaprolactone in mesoporous structure and preparation method and application thereof |
| CN106668948A (en) * | 2017-03-01 | 2017-05-17 | 北京大学第三医院 | Tissue engineering stent based on low-temperature rapid modeling and preparation method thereof |
| CN107823715A (en) * | 2017-10-20 | 2018-03-23 | 昆明理工大学 | A kind of compound porous bone tissue engineering scaffolds of PCL/HA and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112743850A (en) * | 2020-12-23 | 2021-05-04 | 华中科技大学鄂州工业技术研究院 | Preparation method of low-temperature biological 3D printing composite stent |
| CN112972765A (en) * | 2021-02-22 | 2021-06-18 | 苏州大学 | Silk fibroin 3D printing biological ink and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Lam et al. | Scaffold development using 3D printing with a starch-based polymer | |
| Naghieh et al. | Combinational processing of 3D printing and electrospinning of hierarchical poly (lactic acid)/gelatin-forsterite scaffolds as a biocomposite: Mechanical and biological assessment | |
| Mota et al. | Additive manufacturing techniques for the production of tissue engineering constructs | |
| Gomes et al. | Alternative tissue engineering scaffolds based on starch: processing methodologies, morphology, degradation and mechanical properties | |
| Hutmacher | Scaffold design and fabrication technologies for engineering tissues—state of the art and future perspectives | |
| Wu et al. | A “room-temperature” injection molding/particulate leaching approach for fabrication of biodegradable three-dimensional porous scaffolds | |
| Wu et al. | In vitro degradation of three-dimensional porous poly (D, L-lactide-co-glycolide) scaffolds for tissue engineering | |
| KR101929661B1 (en) | Injectable composition for filler comprising porous biodegradable microspheres and water soluble natural polymers | |
| Leong et al. | Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs | |
| More et al. | Polylactic acid (PLA) membrane—significance, synthesis, and applications: a review | |
| Hou et al. | Porous polymeric structures for tissue engineering prepared by a coagulation, compression moulding and salt leaching technique | |
| Jiang et al. | Morphology, wettability, and mechanical properties of polycaprolactone/hydroxyapatite composite scaffolds with interconnected pore structures fabricated by a mini‐deposition system | |
| Gloria et al. | From 3D hierarchical scaffolds for tissue engineering to advanced hydrogel-based and complex devices for in situ cell or drug release | |
| Darus et al. | Techniques for fabrication and construction of three-dimensional bioceramic scaffolds: Effect on pores size, porosity and compressive strength | |
| CN111995793A (en) | Material for low-temperature 3D printing of porous polycaprolactone scaffold and printing method | |
| Zhang et al. | Fabrication of three dimensional polymeric scaffolds with spherical pores | |
| Allaf | Melt-molding technologies for 3D scaffold engineering | |
| Akbarzadeh et al. | Hierarchical polymeric scaffolds support the growth of MC3T3-E1 cells | |
| Ghosh et al. | The double porogen approach as a new technique for the fabrication of interconnected poly (L-lactic acid) and starch based biodegradable scaffolds | |
| Li et al. | Current status of additive manufacturing for tissue engineering scaffold | |
| CN108379668A (en) | A kind of preparation method with hydrophilic polylactic acid porous scaffold material | |
| Piszko et al. | Brief review on poly (glycerol sebacate) as an emerging polyester in biomedical application: Structure, properties and modifications | |
| Liu et al. | Low‐Temperature Deposition Manufacturing: A Versatile Material Extrusion‐Based 3D Printing Technology for Fabricating Hierarchically Porous Materials | |
| Ashraf et al. | The cross-linked polyvinyl alcohol/hydroxyapatite nanocomposite foam | |
| Ghosh et al. | Development of porous lamellar poly (l-lactic acid) scaffolds by conventional injection molding process |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20201127 |
|
| RJ01 | Rejection of invention patent application after publication |