KR101275659B1 - Method for fabricating a three dimensional scaffold using a knitting machine and a scaffold thereof - Google Patents

Abstract

PURPOSE: A method for manufacturing a three dimensional scaffold using a knitting machine and the scaffold manufactured by the same are provided to control the shape, length, and thickness of a fiber, and the knitting method of the fiber, thereby manufacturing the various shapes of the scaffolds with the simple method. CONSTITUTION: A method for manufacturing a three dimensional scaffold using a knitting machine comprises the following steps: a step(S110) of manufacturing a string which has a predetermined diameter and is knitted with biocompatible fibers applied to the knitting machine; a step(S120) of manufacturing a sheet with the strings applied to the knitting machine; a step(S130) of inserting the manufactured sheet into a mold having a certain shape; a step(S140) of mutually coupling the fibers forming the sheet by heating the mold; and a step(S150) of separating the sheet from the mold. [Reference numerals] (S105) Control porosity of a sustentacular cell by controlling interval of a snitch included in a knitting machine; (S110) Manufacture a string which has a predetermined diameter and is knitted with biocompatible fibers applied to the knitting machine; (S120) Manufacture a sheet with the strings applied to the knitting machine; (S130) Insert the manufactured sheet into a mold having a certain shape; (S140) Mutually couple the fibers forming the sheet by heating the mold; (S150) Separate the sheet from the mold

Description

Method for fabricating a three dimensional scaffold using a knitting machine and a scaffold

The present invention relates to a three-dimensional cell support manufacturing method using a knitting machine and a cell support thereof.

Tissue engineering based on mechanical engineering is a research field that induces normal function by restoring, regenerating or replacing damaged or malfunctioning tissues or organs using biotechnology. In tissue engineering, many researches have been carried out to restore the function or damage of organs by artificially making damaged tissues through in vitro cell culture and transplanting them into damaged parts. In order to collect the necessary tissue to culture and proliferate the cells to form new tissues and organs, a three-dimensional scaffold is required.

The cell support is applicable in vivo or in vitro, and can be used as a human volume filler when applied in vivo. The cell support can satisfy the following conditions. First, the cell support maintains the shape of the biological tissue to be regenerated, induces adhesion, proliferation, and differentiation of the cells to be cultured effectively, and plays a role as a supporter with high biocompatibility, and then needs to be safely absorbed and degraded in vivo. There is. However, there is a limit in reproducing the function of each organ of the human body because of limitations of histocompatibility biomaterials that are degraded in vivo and tissue engineering techniques that can differentiate and grow into various biological tissues.

According to the prior art, the cell support is a salt leaching method (Solvent-casting and particulate-leaching technique: AG Mikos et al., Polymer, 35, 1068, 1994), mixed with a single crystal salt and dried to dissolve the salt in water, effervescent salt It is prepared by foaming (gas forming salt method), high pressure gas expansion method (high pressure gas expansion method), emulsion freeze-drying method, phase separation method (phase separation) and the like.

However, these prior arts are inferior in reproducibility, and have limitations in producing a complicated or precise three-dimensional structure. In addition, the pore size and porosity cannot be freely controlled in the fabrication of the porous structure, and the interconnectivity of the pore space is degraded, resulting in cell growth and nutrient supply, diffusion and delivery into the artificial support. There is a difficulty, and it takes a long time to manufacture and requires expensive equipment during manufacturing.

In addition, most of the methods according to the related art use a high temperature or a high pressure, or a solvent such as chloroform or methylene chloride is used as a solvent to dissolve the polymer material. However, such a method requires separate equipment for high temperature and high pressure, and takes a long time to remove the solvent, thus increasing the manufacturing time and raising the problem of controlling the residual amount of the solvent to be kept below 10 ppm. . In particular, in the case of the porous support used for very sensitive body parts, there is a problem that the residual amount of the solvent should be maintained at 1 ppb or less.

The above-described background technology is technical information that the inventor holds for the derivation of the present invention or acquired in the process of deriving the present invention, and can not necessarily be a known technology disclosed to the general public prior to the filing of the present invention.

The present invention provides a three-dimensional cell support manufacturing method and a cell support using a knitting machine for producing a cell support having a different porosity by a simple method by adjusting the set value of the knitting machine.

In addition, the present invention provides a three-dimensional cell support manufacturing method and a cell support using a knitting machine that can manufacture a cell support of various shapes by a simple manufacturing method by adjusting the shape, length, thickness, fiber weaving method, etc. to provide.

The technical problems other than the present invention can be easily understood from the following description.

According to an aspect of the invention, applying the biocompatible fibers to the knitting machine to produce a string having a predetermined diameter and twisted biocompatible fibers; Manufacturing a sheet by applying the twisted string of the biocompatible fibers to a knitting machine; Inserting the manufactured sheet into a mold of a specific shape; Heating the mold to bond the biocompatible fibers forming the sheet to each other; And it provides a three-dimensional cell support manufacturing method using a knitting machine comprising the step of separating the sheet in which the biocompatible fibers are bonded to the template.

Here, in the step of producing the twisted string of the biocompatible fibers, the diameter of the string twisted the biocompatible fibers may be determined corresponding to the thickness of the sheet set in advance.

The mold may have a cylindrical shape, and the inserting of the manufactured sheet into a mold having a specific shape may include inserting a cylindrical sheet formed by rolling the manufactured sheet in one direction to a cylindrical mold.

In the manufacturing of the sheet, the sheet produced by applying the twisted string of the biocompatible fibers to a knitting machine is a flat sheet, and the width of the flat sheet is determined in correspondence with the cylindrical diameter of the cylindrical sheet set in advance. Can be.

In addition, the embodiment may further comprise adjusting the pores of the cell support by adjusting the interval of the knitting needle included in the knitting machine, before the step of producing the twisted string of the biocompatible fibers.

Here, in the step of bonding the biocompatible fibers forming the sheet to each other by heating the mold, the temperature for heating the mold may be a temperature 5 degrees lower than the melting point of the biocompatible fibers to the melting point.

In addition, the biocompatible fiber is polycaprolactone (PCL: Polycaprolactone), the temperature for heating the mold may be 55 to 60 degrees, the heating time may be 10 minutes.

Here, the cross-sectional diameter of the biocompatible fibers may be 30㎛ to 500㎛, the biocompatible fibers may be any one of short fibers, diplexes, triplets and cord yarns.

Other aspects, features, and advantages will become apparent from the following drawings, claims, and detailed description of the invention.

The three-dimensional cell support manufacturing method and the cell support using the knitting machine according to the present invention has the effect of producing a cell support having a different porosity by a simple method by adjusting the set value of the knitting machine.

In addition, the three-dimensional cell support manufacturing method and the cell support using the knitting machine according to the present invention can manufacture a cell support of various shapes by a simple manufacturing method by controlling the shape, length, thickness, the way of weaving fibers, etc. It has an effect.

1 is a flow chart of a three-dimensional cell support manufacturing method using a knitting machine according to an embodiment of the present invention.
2 to 8 is a view showing in order the concept of manufacturing a cell support using a knitting machine according to an embodiment of the present invention.
9 to 14 are photographs showing the process of manufacturing the actual cell support using a three-dimensional cell support manufacturing method using a knitting machine according to an embodiment of the present invention.
15a and 15b are optical micrographs of the cell support produced by the three-dimensional cell support manufacturing method using a knitting machine according to an embodiment of the present invention.
16a to 16d are electron micrographs of the cell support produced by the three-dimensional cell support manufacturing method using a knitting machine according to an embodiment of the present invention.

While the invention is susceptible to various modifications and alternative forms, specific embodiments thereof are shown by way of example in the drawings and will herein be described in detail. It is to be understood, however, that the invention is not to be limited to the specific embodiments, but includes all modifications, equivalents, and alternatives falling within the spirit and scope of the invention.

Terms including ordinal numbers such as first and second may be used to describe various components, but the components are not limited by the terms. The terms are used only for the purpose of distinguishing one component from another.

When a component is referred to as being "connected" or "connected" to another component, it may be directly connected to or connected to that other component, but it may be understood that other components may be present in between. Should be.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Singular expressions include plural expressions unless the context clearly indicates otherwise. In this specification, the terms "comprises" or "having" and the like refer to the presence of stated features, integers, steps, operations, elements, components, or combinations thereof, But do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, or combinations thereof.

The term " part, "" module," " means, "or the like, which is described in the specification, refers to a unit for processing at least one function or operation and may be implemented by hardware or software or a combination of hardware and software .

In the following description of the present invention with reference to the accompanying drawings, the same components are denoted by the same reference numerals regardless of the reference numerals, and redundant explanations thereof will be omitted. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. In the following description, well-known functions or constructions are not described in detail since they would obscure the invention in unnecessary detail.

1 is a flow chart of a three-dimensional cell support manufacturing method using a knitting machine according to an embodiment of the present invention.

This embodiment is characterized by producing a cell support having a desired porosity using a knitting machine. That is, the present embodiment is characterized by producing a cell support having a different porosity by a simple method by adjusting the set value of the knitting machine.

Knitting machine used in the present invention is a machine for supplying a predetermined thread to the needle (needle), the knitting needle makes a loop (nose), the nose is a machine that produces the knitted fabric in the longitudinal and transverse direction, and the type Basic techniques for knitting machines, such as operating principle, knitting cycle, etc., are readily available to those skilled in the art, and thus detailed descriptions thereof will be omitted.

Knitting machine applicable to the present invention can be a product of various manufacturers, this embodiment used a knitting machine of the model name KH-111 of BROTHER, Japan. This product consists of a main body in which a large number of knitting needles are arranged, and a carriage that twists the fibers caught in the knitting needles to produce a knitted fabric. Of course not.

In step S105, the pore of the cell support is controlled by adjusting the tension applied to the biocompatible fibers supplied to the knitting machine. Specifically, by adjusting the number of dials to determine the tension of the knitting machine, it is possible to adjust the pitch of the string corresponding to the desired porosity. That is, the knitting machine needs a means for adjusting the tension by pulling the yarn to be fed in a specific direction, the tightness of the string spacing of the fabric can be determined by this tension, the line spacing in this embodiment is Porosity can be determined.

In step S110, a biocompatible fiber is applied to a knitting machine to produce a twisted string having a predetermined diameter. The diameter of the string in which the biocompatible fibers are twisted may be determined corresponding to the thickness of the sheet to be described later. Cords twisted with biocompatible fibers may be produced by weaving in various patterns, and various cell supports may be formed according to the patterns.

The biocompatible fiber used in the present embodiment may be any one of short fibers, two-ply yarns, three-ply yarns, and cord yarns. In addition, the biocompatible fibers may be biocompatible thermoplastic polymer sutures. Specifically, the biocompatible fibers may be formed of polycaprolactone (PCL: Polycaprolactone) or polydioxanone (PDO: Polydioxanone). In addition, biocompatible fibers for preparing cell supports include polypropylene (PP: Polypropylene), polyamino acids, polyanhydrides, polyorthoesters, polyglycolic acid (PGA), polylactic acid (PLA), and copolymers thereof. Lactic-glycolic acid (PLGA) or the like. In addition, the biocompatible short fiber longitudinal section diameter (width) may be 30 μm to 500 μm.

Since the porosity of the cell support, its shape, etc. can be determined by adjusting the shape, length, thickness, fiber weaving method, etc. of the biocompatible fiber, the present invention is characterized by producing a cell support having various shapes by a simple manufacturing method.

The twisted string of biocompatible fibers can be produced by the knitting principle of the knitting machine, for example, by forming two or three needle noses from the biocompatible fibers and twisting the needle noses together. Thereafter, the carriage of the knitting machine is repeatedly moved from side to side to produce a long twisted line having a length sufficient to produce a sheet of a desired size. As described above, a technique for producing knitted fabric using fibers is obvious to those skilled in the art, and thus detailed description thereof will be omitted.

In step S120, a sheet is manufactured by applying the twisted string of the biocompatible fibers to the knitting machine. In other words, a long cord twisted with biocompatible fibers is put into a knitting machine to make a needle nose corresponding to a preset diameter when fabricating a cell support. Here, the diameter refers to a specific size of the completed cell support, for example, when the cell support is made of a cylindrical may refer to the diameter of the cylindrical. Thereafter, the carriage of the knitting machine is moved to the left and right to produce a sheet having a predetermined length.

According to this application, since the yarn constituting the sheet is a twisted string of the above-mentioned biocompatible fibers, pores are formed by itself, and pores are formed even when purging or enclosing as shown in the drawing, thereby producing a porous cell support. .

Here, the shape of the sheet produced by applying the twisted string of biocompatible fibers to the knitting machine may be initially planar. Since such a planar sheet can be rolled up to be a cylindrical sheet as described above, the width of the planar sheet can be determined corresponding to the cylindrical diameter of a predetermined cylindrical sheet. That is, when the cylindrical sheet is formed by winding the planar sheet so that the inside is densely filled, the larger the width of the planar sheet is, the larger the cylinder diameter of the cylindrical sheet is, so that the size of the planar sheet width corresponds to the cylindrical diameter of the cylindrical sheet to be manufactured. Can be determined.

In step S130, the manufactured sheet is inserted into a mold of a specific shape. Here, the shape of the mold may be a hollow cylinder inside. The fabricated flat sheet can be rolled in one direction into a cylindrical sheet and then inserted into a cylindrical mold.

In step S140, the biocompatible fibers forming the sheet by heating the mold are bonded to each other. Here, the temperature for heating the mold may be near the melting point of the biocompatible fibers, for example, from a temperature 5 degrees below the melting point of the biocompatible fibers to its melting point. Specifically, for example, when the biocompatible fiber is polycaprolactone (PCL: Polycaprolactone), the temperature for heating the mold may be 55 to 60 degrees, the heating time may be 5 to 15 minutes.

In step S150, the sheet to which the biocompatible fibers are bound is separated from the mold to prepare a three-dimensional cell support. When the above-described mold is cylindrical, the cylindrical sheet formed by rolling the manufactured sheet in one direction is inserted into the cylindrical mold, and the biocompatible fibers of the cylindrical sheet are bonded to each other by heating the cylindrical mold into which the cylindrical sheet is inserted, and then the biocompatible fiber. The bonded cylindrical sheet may be separated from the cylindrical mold to prepare a cell support.

2 to 8 is a view showing in order the concept of manufacturing a cell support using a knitting machine according to an embodiment of the present invention.

Referring to FIG. 2, a plurality of needle noses are formed in the biocompatible fibers, and the plurality of knitting needles 101 (1) to 101 (3) are inserted into the needle noses to twist the biocompatible fibers through left and right repetitive movements 110. ).

Referring to FIG. 3, a plurality of needle noses are made in the twisted string 110 of the manufactured biocompatible fibers, and the needle noses are inserted into the knitting needles 101 (1) to 101 (3) of the knitting machine in a left-right repeating motion. Through the flat sheet 120 is manufactured. 3 shows the purl side of the flat sheet 120 and FIG. 4 shows the purl side of the flat sheet 120.

Referring to FIG. 5, a method of separating flat sheet 120 from a knitting machine is shown. The needle nose of the flat sheet 120 is finished by being sequentially inserted into adjacent needle noses, and at the same time the flat sheet 120 can be separated from the knitting machine.

Referring to FIG. 6, the cylindrical sheet 130 may be manufactured by rolling the flat sheet 120 in one direction. Referring to FIG. 7, the manufactured cylindrical sheet 130 is inserted into the cylindrical mold 140 to fix the shape.

Referring to FIG. 8, the cylindrical mold 140 into which the cylindrical sheet 130 is inserted may be placed at predetermined time and temperature conditions on the support 160 on the hot plate 150. The cover 170 allows the cylindrical sheet 130 to be heated evenly and maintains the temperature of the hot plate 150. The support 160 prevents the heat of the hot plate 150 from being transmitted only to a portion of the cylindrical mold 140, and may be a good conductor of heat.

9 to 14 are photographs taken of the experimental process of reproducing the above-described processes using the three-dimensional cell support manufacturing method using a knitting machine according to an embodiment of the present invention. FIG. 9 illustrates a process of manufacturing a twisted string of biocompatible fibers, FIG. 10 illustrates a process of manufacturing a sheet having a planar shape, FIG. 11 illustrates a process of measuring a cylindrical sheet, and FIG. 12 inserts a cylindrical sheet into a cylindrical mold. 13 shows the dimensions of the three-dimensional cell support dissolved in heat. Fig. 14 shows a cylindrical sheet cut to a predetermined length (about 5 mm) as needed. 14A and 14B show a cylindrical sheet manufactured using fibers having a cross-sectional diameter of 80 μm, and (C) and (D) having a fiber of 200 μm.

15a and 15b are optical micrographs of the cell support produced by the three-dimensional cell support manufacturing method using a knitting machine according to an embodiment of the present invention. FIG. 15A (A) shows a cell support fabricated by weaving biocompatible fibers having a cross-sectional diameter of 80 µm and having an interfiber spacing (pore size) of 230.25 µm. FIG. 15A (B) shows a cell support prepared from biocompatible fibers having a cross-sectional diameter of 80 μm and having an interfiber spacing of 332.84 μm. FIG. 15B (C) shows a cell support fabricated by weaving biocompatible fibers having a cross-sectional diameter of 200 μm and having an interfiber spacing of 74.00 μm. FIG. 15B (D) shows a cell support prepared from biocompatible fibers having a cross-sectional diameter of 200 μm and having an interfiber spacing of 374.61 μm.

16a to 16d are electron micrographs of the cell support produced by the three-dimensional cell support manufacturing method using a knitting machine according to an embodiment of the present invention. Figure 16a is produced by weaving biocompatible fibers having a cross-sectional diameter of 80μm, showing a cell support having an interfiber spacing of 230.25μm. FIG. 16B shows a cell support made from biocompatible fibers having a cross-sectional diameter of 80 μm with an interfiber spacing of 332.84 μm. FIG. 16C shows a cell support fabricated by weaving biocompatible fibers having a cross-sectional diameter of 200 μm and having an interfiber spacing of 74.00 μm. FIG. 16D shows a cell support made from biocompatible fibers having a cross-sectional diameter of 200 μm with an interfiber spacing of 374.61 μm.

The three-dimensional cell support manufacturing method using the knitting machine according to the present invention can be implemented in the form of program instructions that can be executed by various computer means can be recorded on a computer readable medium. That is, the recording medium may be a computer-readable recording medium having recorded thereon a program for causing a computer to execute the steps described above. In this case, the present embodiment can be produced in large quantities by interlocking with the electronic system including the motor described above.

The computer readable medium may include a program command, a data file, a data structure, etc. alone or in combination. The program instructions recorded on the medium may be those specially designed and constructed for the present invention or may be available to those skilled in the art of computer software. Examples of the computer-readable recording medium include magnetic media such as a hard disk, a floppy disk and a magnetic tape, optical recording media such as CD-ROM and DVD, magnetic recording media such as a floppy disk Optical media, and hardware devices specifically configured to store and execute program instructions such as ROM, RAM, flash memory, and the like.

The medium may be a transmission medium such as an optical or metal line, a wave guide, or the like, including a carrier wave for transmitting a signal designating a program command, a data structure, or the like. Examples of program instructions include not only machine code generated by a compiler, but also high-level language code that can be executed by a computer using an interpreter or the like. The hardware device described above may be configured to operate as one or more software modules to perform the operations of the present invention.

In the above, the three-dimensional cell support manufacturing method using a knitting machine according to an embodiment of the present invention has been described a specific shape and material according to an embodiment, but is not necessarily limited to this, other shapes than the shape If other implementations or use of different materials do not differ in the overall operation and effects such other configurations may be included in the scope of the present invention, each component and / or function described in each embodiment may be implemented in combination with each other in combination Can be.

Those skilled in the art will appreciate that various modifications and changes can be made in the present invention without departing from the spirit and scope of the invention as set forth in the claims below.

101 (1) to 101 (3): knitting needle 110: twisted string of biocompatible fibers
120: flat sheet 130: cylindrical sheet
140: cylindrical mold 150: hot plate
160: support 170: cover

Claims (10)

Applying a biocompatible fiber to a knitting machine to produce a string having a predetermined diameter and twisting the biocompatible fiber;
Manufacturing a sheet by applying the twisted string of the biocompatible fibers to a knitting machine;
Inserting the manufactured sheet into a mold of a specific shape;
Heating the mold to bond the biocompatible fibers forming the sheet to each other; And
Method for producing a three-dimensional cell support using a knitting machine comprising the step of separating the sheet in which the biocompatible fibers are bonded.
The method according to claim 1,
In the step of producing the twisted string of the biocompatible fibers,
Method for producing a three-dimensional cell support using a knitting machine, characterized in that for determining the diameter of the string twisted biocompatible fibers corresponding to the thickness of the sheet set in advance.
The method according to claim 1,
The mold is cylindrical in shape,
Inserting the produced sheet into a mold of a specific shape,
Method for producing a three-dimensional cell support using a knitting machine, characterized in that for inserting the cylindrical sheet formed by rolling the produced sheet in one direction into a cylindrical mold.
The method according to claim 3,
In the step of manufacturing the sheet,
The sheet produced by applying the twisted string of the biocompatible fibers to the knitting machine is a flat sheet, and the width of the flat sheet is determined in correspondence to the cylindrical diameter of the cylindrical sheet set in advance. 3D cell support production method.
The method according to claim 1,
Before the step of producing the twisted string of the biocompatible fibers,
And adjusting the pores of the cell support by adjusting the tension applied to the biocompatible fibers supplied to the knitting machine.
The method according to claim 1,
Heating the mold to bond the biocompatible fibers forming the sheet to each other,
The temperature for heating the mold is a temperature of 5 degrees lower than the melting point of the biocompatible fiber to the melting point, characterized in that for producing a three-dimensional cell support using a knitting machine.
The method of claim 6,
The biocompatible fiber is polycaprolactone (PCL: Polycaprolactone), the temperature for heating the mold is 55 to 60 degrees, the heating time is a three-dimensional cell support manufacturing method using a knitting machine, characterized in that 10 minutes.
The method according to claim 1,
Cross-sectional diameter of the biocompatible fiber is a method for producing a three-dimensional cell support using a knitting machine, characterized in that 30㎛ to 500㎛.
The method according to claim 1,
The biocompatible fiber is a three-dimensional cell support manufacturing method using a knitting machine, characterized in that any one of a single fiber, two-ply yarn, three-ply yarn and cord yarn.
A cell support produced using the method of any one of claims 1 to 9.

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