KR20190037468A - Methods of Fabrication of Nano/microrod based on aligned electrospun fibers and its application of injectable nano/microrod system - Google Patents

Abstract

The present invention relates to a method for manufacturing an electrospun fiber nano/micro rod and an injectable agent using the same. The method comprises: an electrospinning step of performing electrospinning using a biodegradable polymer; a fiber collecting step of collecting the electrospun fibers to a collector; a cutting step of cutting the collected fibers through a cutting means to a predetermined length; and a separating step of separating the cut fibers from the cutting means. In the cutting step, the fibers are stretched so that the length can be adjusted to 10 to 100 nm. According to the present invention, nano/micro rods can be easily manufactured from aligned nanofibers.

Description

TECHNICAL FIELD [0001] The present invention relates to an electrospun fiber-based nano / micro rod manufacturing method,

 The present invention relates to a method of preparing an nano / micro rod based on electrospun fiber and a syringe injecting agent prepared from the same, and more particularly, to an electrospinning device and a homemade collector using various biodegradable polymers having high ductility including polycaprolactone A method of producing a single nano / micro rod after manufacturing an ordered electrospun fiber, and an injection injecting agent in which the nano / micro rod is mixed with a carrier such as hyaluronic acid.

In the past, it has been used to manufacture injectable injectable polycaprolactone (PCL), which is used as a medical polymer material such as a drug release modifier and surgical suture for decades and assures the collagen synthesis and is secured with the approval of FDA and CE. In Patent Application No. 10-2015-0094455, a polycaprolactone raw material was prepared using a cryogenic mill method, and hyaluronic acid was diluted with distilled water (94 cc) The present invention relates to a composition comprising 5% of polycaprolactone microspheres, and using the filler extract for restoring skin tissue to be used for restoring skin. Elancera is a composition comprising a polycaprolactok component, which is a main component of a tissue restorative filler, A carrier composed of gels mimicking a cryogenic mill which is processed is dissolved in carboxymethylcellulose (ca. rboxymethylcelluose, CMC) to hyaluronic acid (hyaluronic acid). Cryomilled polycaprolactone microspheres, the main component of Elance and filler extract, are self-generated collagen (Type I, Type III) responsible for resilience and regeneration in their skin and naturally produced collagen over time Due to the effect of softening the filled part after filler treatment, the effect is maintained for 2 years after the first injection, and it is decomposed into water and carbon dioxide by hydrolysis, and is completely decomposed and absorbed and discharged with almost no residual ratio.

However, it is known that the biodegradability of polycaprolactone is determined not by the type of polycaprolactone but by the molecular weight. When the molecular weight of polycaprolactone is Mn = 80000, 60000, 40000, the half-life is 2 years, 1 year and 6 months In the case of nano / microstructures prepared by using polycaprolactone of the same molecular weight, the half-life is determined not by the shape but by the molecular weight. When the molecular weight is the same, the half-life is also the same, but the surface area is larger than that of the microsphere. And a polycaprolactone nano / micro rod structure that is less affected by gravity is needed.

Korean Patent Application No. 2010-7004604 also discloses a method for preparing injectable injectable polycaprolactone microspheres using solubilized polycaprolactone, a surfactant and a mixed solution having a viscosity ranging from 1 to about 400,000 cP And then the biodegradable injectable gel containing a carrier and an active ingredient is prepared. The thus prepared injectable gel is applied to an implant, a filler and a cosmetic lt; RTI ID = 0.0 > cosmetic < / RTI > And which can avoid agglomeration, neddle clogging and nodule forming at the time of implantation, and which have excellent properties such as flow characteristics due to essentially spherical microspheres Biodegradable medical implants with reabsorption properties are required, and polycaprolactone microspheres using surfactants have been developed. However, as claimed in the above-mentioned patent, it is claimed that spherical microspheres are essential for manufacturing a scanning gel, but Patent Application No. 10-2017-7007215, which manufactures injectable complexes containing nanofiber structures and Subramanian et. al. 2015 Materials Science and Engineering C, 51, 16-17.

Meanwhile, Korean Patent Application No. 2017-7007215 claims that a scan injectable scaffold complex comprising hyaluronic acid and a polycaprolactone nanostructure can be prepared and applied to a soft tissue. The nanostructures were made by mixing polyethylene glycol diacrylate (PEG-DA) and thiolated hyaluronic acid (HA-SH) in a maleimide (MAL) conjugated fiber nanorod. The thiol groups in hyaluronic acid were reacted with maleic anhydride or polyethylene glycol end-capped diacryl groups on PCL nanorods to produce hydrogel nanostructures. In the process, random meshes prepared using electrospinning are subjected to a multistage process to attach the maleimide groups to the mesh surface. In short, the fibers are plasma treated to have functional groups on the fiber surface, conjugated with acrylic acid through initiation of UV photopolymerization, reacted with EDC and diazimine to form primary amines and then react with SMCC to form maleimide Attach the group. It reacts with thiol groups in hyaluronic acid to form a nanostructure. In this process, the functionalized fiber mesh was immersed in liquid nitrogen and cut to 5x5 mm and pulverized for 20 minutes using mortar and pestle. Freezing (Miller 6770, SPEX SamplePrep, Metuchen, NJ) was also used to prepare sections of polyacrylic acid (PAA) immobilized fibers.

On the other hand, after spinning with PCL (Mn = 40,000) in Clo 32, 1366-1374, Knotek et al 2012 Materials Science and Engineering, cryomilling with liquid nitrogen was used to produce various types of particles, . In the case of fiber particles, the length was 300-1000 μm, the width was about 5-50 μm, the typical size of the fiber slice was about 50 μm, the maximum length was 300 μm, the size of the inner fiber structure was 10-100 μm, The size of the missing lumps was 50-300 μm. In the case of the thin plate, the size was 30-40 μm and the thickness was less than 1 μm. In the case of nanoparticles, the diameter was 100-150 nm and the length was 40 μm. Nano / microfibers of various shapes and sizes were prepared by cryomilling the electrospun fibers, but disadvantage is that they can not produce single or single size nano / microfibers.

In Korean Patent Application No. 2014-0117060, PLA (poly L-lactide) was used to prepare electrospun fibers. The prepared electrospun net was cut into small pieces, which were then mixed with 10 wt% hexamethylenediamine , HMDA) was dissolved in isopropyl alcohol (IPA), and the mixture was strongly mixed at 200 rpm for 30 minutes in a shaking incubator (SI-600R, Jeio Tech, Korea) at 37 ° C for fragmentation. The length of the fabricated particles varied from about 10 to 80 μm (average length: 28.9 μm), and the fiber diameter remained almost the original fiber diameter due to the relatively short amino decomposition time. Also, et. al. Due to the easy destruction of amorphous regions between lamellar crystalline domains under shear-stress at the 2008 Macromolecule Rapid Communication 29, 1231-1236, various cyclic lengths (average length: 1.2-13.8 μm ) Were prepared by chemical methods such as aminolysis of PLLA network.

Korean Patent Application No. 2010-7004604 Korean Patent Application No. 2017-7007215 Korean Patent Application No. 2014-0117060

In order to solve the above problems, it is an object of the present invention to manufacture a nano / micro rod capable of controlling the length by using PCL and various biopolymers.

It is also an object of the present invention to develop a nano / micro rod type in which nano / micro rods are mixed with a carrier such as hyaluronic acid to enable injection.

According to an aspect of the present invention, there is provided an electrospinning method, comprising: electrospinning an electrospinning process using a biodegradable polymer; A fiber collecting step of collecting the electrospun fiber to a collector; A cutting step of cutting the collected fibers through a cutting means to a predetermined length; A separation step of separating the cut fibers from the cutting means; The present invention also provides a method of manufacturing an electrospun fiber-based nano / micro rod, characterized in that it is stretched so as to be adjustable in length from 10 to 100 mm in the cutting step.

In addition, according to the present invention, the nano / micro rod cut after the cutting step may be frozen in liquefied nitrogen and then subjected to a freezing and cutting step capable of cutting it to a length of 100 m to 100 mm, Of the present invention.

According to the present invention, the biodegradable polymer is selected from the group consisting of polycaprolactone (PCL Mn = 80000, 60000, 45000), poly (L-lactic acid) (PLLA), poly (D, L- (PGA), poly (lactic-glycolic acid) (PLGA), poly methyl metaacrylate, poly (hydroxyalkanoate), polydioxanone (PDS), polytrimethyl A method for producing an electrospun fiber-based nano / micro rod, characterized in that the compound is at least one compound selected from the group consisting of phosphate, carbonate, carbonate, carbonate, carbonate, carbonate, to provide.

According to the present invention, the biodegradable polymer may be prepared by mixing a linear polymer, a copolymer, a terpolymer or other homo / co / ter polymer Wherein the nano / micro rods are manufactured by a method of manufacturing an electrospun fiber-based nano / micro rod.

According to the present invention, there is also provided a method of manufacturing an electrospun fiber-based nano / micro rod, characterized in that the collector causes the radiated fibers to emit in a side-by-side fashion without overlapping each other and the fibers are attached to two points of the collector to provide.

Also, according to the present invention, there is provided a method of manufacturing an electrospun fiber-based nano / micro rod characterized by being in the shape of two bars having a C shape or a spaced apart shape.

According to the present invention, the cutting means is a solid material capable of cutting and cutting the spun fibers, so that the fibers can be cut at a position near the point where the fibers are attached to the collector. A method of manufacturing a micro-rod is provided.

According to the present invention, there is also provided an injection injecting agent which is prepared by mixing nano / micro rods prepared by the above-described method with a carrier and injecting the injected injectable agent, wherein the carrier comprises hyaluronic acid, carboxymethylcellulose wherein at least one of carboxymethyl cellulose, collagen, alginic acid, gelatin, elastin, saline, and distilled water is used.

In addition, according to the present invention, the nano / micro rod provides an injecting agent which can be used as any one of an implant, a filler, and a scaffold.

The method for preparing an electrospun fiber-based nano / micro rod according to the present invention and the injection injecting agent prepared therefrom can easily produce nano / micro rods from a regulated nanofiber made of a soft biocompatible material such as polycaprolactone have.

The nano / micro rod manufactured by the method of manufacturing an electrospun fiber-based nano / micro rod according to the present invention can be adjusted to have a length of 100 μm to 10 cm.

The nano / micro rod manufactured by the method of manufacturing an electrospun fiber-based nano / micro rod according to the present invention can be used as an injecting agent for forming a three-dimensional network after mixing with a carrier such as hyaluronic acid.

The method of preparing an electrospun fiber-based nano / micro rod according to the present invention and the injection injecting agent containing nano / micro rods prepared therefrom can be applied to cell supports, fillers, implants and the like.

FIG. 1 is a schematic view illustrating a manufacturing process of an electrospun fiber-based nano / micro rod according to an embodiment of the present invention.
FIG. 2 is a schematic view illustrating a method of collecting and cutting fibers emitted in the method of manufacturing an electrospun fiber-based nano / micro rod according to an embodiment of the present invention.
3 is a micrograph of a nano / micro rod on a glass cutting means having a width of 26 mm in Example 1 of the present invention.
FIG. 4 is a micrograph of a sample taken on a glass after separating a nano / micro rod into an ethanol solution using a sonicator in Example 1 of the present invention.
Fig. 5 is a micrograph showing a state where the nano / micro rod is immersed in liquefied nitrogen in Example 3 and then freezed once with a cutter.
FIG. 6 is a micrograph showing a state where the nano / micro rod is immersed in liquefied nitrogen and then subjected to random freezing with a cutter in Example 3. FIG.
7 is a photomicrograph of an injection injecting agent mixed with a carrier (hyaluronic acid) of freeze-cut nano / micro rods having a length of 25 mm in Example 6 to form a porous network with a three-dimensional structure.
8 is a micrograph of a randomly frozen single nano / micro rod prepared in Example 6 mixed with a carrier to form a porous structure.
FIG. 9 is a micrograph of a single nano / micro rod randomly frozen in Example 6 mixed with a carrier. FIG.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in detail with reference to the accompanying drawings. First, it should be noted that, in the drawings, the same components or parts have the same reference numerals as much as possible. In the following description of the present invention, a detailed description of known functions and configurations incorporated herein will be omitted so as to avoid obscuring the subject matter of the present invention.

As used herein, the terms "substantially", "substantially", and the like are used herein to refer to a value in or near the numerical value when presenting manufacturing and material tolerances inherent in the meanings mentioned, Absolute numbers are used to prevent unauthorized exploitation by unauthorized intruders of the mentioned disclosure.

The present invention relates to a method for producing an nano / micro rod based on an electrospun fiber and an injection injecting agent using the same, the electrospinning step of electrospinning using a biodegradable polymer; A fiber collecting step of collecting the electrospun fiber to a collector; A cutting step of cutting the collected fibers through a cutting means to a predetermined length; And a separating step of separating the cut fibers from the cutting means, wherein the nano / micro rods are manufactured by extending and cutting to a length of 10 to 100 mm in the cutting step, have.

FIG. 1 is a schematic view illustrating a manufacturing process of an electrospun fiber-based nano / micro rod according to an embodiment of the present invention.

FIG. 2 is a schematic view illustrating a method of collecting and cutting fibers emitted in the method of manufacturing an electrospun fiber-based nano / micro rod according to an embodiment of the present invention.

The present invention consists of an electrospinning step, a collecting step, a cutting step and a separating step, and further includes a freezing step after the cutting step.

In the electrospinning step, an electrospinning device is used to emit biodegradable polymer fibers.

The electrospinning apparatus is generally used, and the electrospinning apparatus to be used is not particularly limited.

A biodegradable polymer and a solvent are put into the electrospinning device to make it into a solution state, and then it is spun.

Here, biodegradable polymers include polycaprolactone (PCL), poly (L-lactic acid) (PLLA), poly (D, L-lactic acid) PDLLA), poly (glycolic acid) (PGA) (PLGA), poly methyl metaacrylate, poly (hydroxyalkanoate), polydioxanone (PDS), polytrimethylenecarbonate, hydroxyapatite, fibril ), Alginate, calcium triphosphate, and the like.

The biodegradable polymer may be a mixture of a linear polymer, a copolymer, a terpolymer, or another kind of homo / co / ter polymer.

In the case of polycaprolactone (PCL), Mn = 80000, 60000 and 45000 can be used.

Electrospinning can produce nano- or micro-rods, which can be controlled by controlling the diameter of the needle tip used when spinning in an electrospinning device or by adjusting the spacing between collectors that collect needle tips and fibers upon spinning, Diameters of nanofibers aligned from meters to a few micrometers can be produced.

In the collecting step of the present invention, collecting the discharged fibers with electrospinning causes the fibers to be radiated side by side to the collector.

The collector may be in the form of a C-shaped or two separated bars. The two bars in the two spaced apart bars may be parallel or non-parallel.

The collector is characterized in that the radiated fibers are allowed to emit in a side-by-side fashion without overlapping each other, wherein the fibers are attached to two points of the collector.

The collector may have a U-shape and a gap between the upper and lower bars and a distance between the two bars may be 10 to 100 mm. The fibers thus collected can be cut to a certain size upon subsequent cutting.

Referring to FIG. 2 (a), the fibers are radiated in parallel so as to span the C-shaped collector. The radiated fibers may be arranged so that they do not overlap with each other but are arranged side by side so as not to stick together.

The cutting step is followed by the collecting step, wherein the cutting step uses the cutting means to cut the spun fibers.

The fibers radiated through the cutting means in the cutting step can be stretched from the collector and cut off. (See Fig. 2 (b)).

The cutting means is a solid material that can cut and cut the spun fibers so that they can be cut at a location near the point where the fibers are attached to the collector.

The cutting means is not particularly limited in terms of shape, shape and material, such as glass, C-shaped stainless steel, wire, plastic material, rectangular stainless steel wire, If possible.

Separation step

The cut fibers can be separated from the cutting means, and the fibers can be separated from the cutting means using a sonicator. It is immersed in a liquid substance such as ethanol.

In addition, a liquid such as distilled water, ethanol, or methanol can be flowed in place of the sonicator to separate the cut fibers from the cutting means. Solutions such as ethanol and distilled water containing separated fibers were naturally dried for two days or mixed with a carrier such as hyaluronic acid to make lyophilized and injectable solutions.

Further, the present invention can further carry out a freezing cutting step after the cutting step.

The cut fibers were thoroughly dipped in liquefied nitrogen prior to separation from the cutting means and were freeze-cut using a cutter. Or cutting means with cut fibers were immersed in ethanol or distilled water, the liquefied nitrogen was sufficiently poured to freeze, and then cut using a cutter.

That is, the nano / micro rod cut in the cutting step can be frozen in liquefied nitrogen and then freeze-cut using a cutter to a desired length from 100 μm to 100 mm.

In addition, the present invention can utilize the nano / micro-rod manufactured in the electrospinning step, the collecting step, the cutting step and the separation step or the nano / micro-rod prepared by adding the frozen cutting step after the cutting step as an injection injecting agent.

The nano / micro-rod may be mixed with a carrier to prepare an injection injecting agent capable of injecting injections. Examples of the carrier include hyaluronic acid, carboxymethyl cellulose, collagen, alginic acid at least one of alginic acid, gelatin, elastin, saline, and distilled water may be used.

In addition, the nano / micro rod can be used as an injection injecting agent that can be used as any one of an implant, a filler, and a scaffold.

Hereinafter, embodiments of the present invention will be described in detail.

Example 1

Electrospinning of polycaprolactone (Sigma Aldrich Mn = 80000, 45000), the electrospinning collector formed a stainless steel C-shaped collector to allow the electrospun fibers to be aligned above and below the C-shaped collector. The length of the U-shaped collector is about 150 mm, and the width of the upper and lower portions is adjusted to 10 to 100 mm, so that a 10 to 100 mm of aligned fibers can be produced. The spinning parameters were 12 to 15 wt% of polycaprolactone in chloroform-methanol at 80 vol% / 20 vol%, and the solution was set at 21 to 15 cm away from the target U- ≪ / RTI > gauge blunt needle. The needle voltage was 0 kV and the target plate was negatively biased to a voltage of -4.9 kV and then emitted for 30 seconds. As the distance between the needle and the collector increased from 5 cm to 15 cm, the diameter of the fiber could be adjusted from 5 μm to 300 nm. In particular, when the distance between the needles and the collector was 5 cm, the fiber diameter was 2-5 μm.

The fibers arranged in the C-shaped electrospinning collector were cut to a length of 10 to 76 mm by using glass as a cutting means. The width of the glass microscope slides (76 x 26 x 1 mm) was adjusted to be 10 to 76 mm to obtain a C-shaped electrospinning collector The nano / micro rods can be cut by stretching the aligned nano / micro fibers.

To make the desired length of nano / micro-rod, the width of the glass-made microscope slide was adjusted / processed to cut the electrospun fiber to the desired length. After the glass with cut fiber was immersed in ethanol solution, the glass and nano / micro rod were separated using a sonicator for 30 seconds, and ethanol was completely dried to prepare nano / micro rod.

3 is a micrograph of a nano / micro rod on a glass cutting means having a width of 26 mm in Example 1 of the present invention.

FIG. 4 is a micrograph of a sample taken on a glass after separating a nano / micro rod into an ethanol solution using a sonicator in Example 1 of the present invention.

Referring to FIG. 3, it can be seen that when the fibers radiated to the collector are cut out by cutting through the glass, which is the cutting means, there is a nano / micro rod which is the fiber radiated on the glass. It can be seen that the fiber can be cut by cutting means such as glass.

Referring to FIG. 4, a nano / micro rod is separated from the glass into an ethanol solution using a sonicator, and there is no nano / micro rod on the gliss.

Example 2

The procedure of Example 1 was repeated,

The fibers in the collector were cut using a C-shaped cutting means as a cutting means to separate the nano / micro rods into ethanol by a C-shaped cutting means.

Example 3

The procedure of Example 1 was repeated,

The nano / micro rod was immersed in liquefied nitrogen and then freezed with a cutter. The nano / micro rod was collected in a 26 mm wide microscope slide glass. After the glass with the cut fiber was immersed in ethanol solution, the glass and nano / micro rod were separated by using a sonicator or a solution such as ethanol on a glass cut with nano / micro rod for about 30 seconds, and ethanol Completely dried to prepare a nano / micro rod.

Fig. 5 is a micrograph showing a state where the nano / micro rod is immersed in liquefied nitrogen in Example 3 and then freezed once with a cutter.

FIG. 6 is a micrograph showing a state where the nano / micro rod is immersed in liquefied nitrogen and then subjected to random freezing with a cutter in Example 3. FIG.

Referring to FIG. 5, when both ends of a stretched nano / micro rod having a length of 26 mm were immersed in liquid nitrogen and then cut, the length of the frozen cut nano / micro rod was 25 mm

Referring to FIG. 6, randomly freeze-cut nano / micro rods have an average diameter of 3 μm and a length of 100-400 μm.

Example 4

The procedure of Example 1 was repeated, except that

Both ends of the stretched nano / micro rod with a length of 76 mm were prepared by freezing.

The length of the nano / micro rod cut by freezing as in Example 4 was 75 mm. Therefore, it was confirmed that the length of the nano / micro rods cut by freezing is about 100 μm-75 mm.

Example 5

The procedure of Example 1 was repeated,

The nano / micro rods that had been completely dried with ethanol were pipetted using primary distilled water or ethanol, and then distilled water or ethanol containing nano / micro rods in liquid nitrogen was sufficiently cooled by using liquid nitrogen. Using a cutter The length of the nano / micro rod after the random cutting and the frozen cutting was about 100-1000 mu m.

Example 6: Injection injected with a mixture of a single fiber prepared by PCL and a carrier (hyaluronic acid)

The nano / micro rod prepared in Example 3 was mixed with an aqueous solution of 20 mg / ml of hyaluronic acid (Wako, molecular weight: 1,500,000) and a 23 G needle tip After passing, nano / micro rods were observed.

7 is a photomicrograph of an injection injecting agent mixed with a carrier (hyaluronic acid) of freeze-cut nano / micro rods having a length of 25 mm in Example 6 to form a porous network with a three-dimensional structure.

Referring to FIG. 7, a nano / micro rod having a length of 25 mm is mixed with a carrier and has a three-dimensional network structure even after passing a 23G needle tip. Nano / micro rods with a length of 25 mm form a three-dimensional structure that forms a porous network of nano / micro rods.

8 is a micrograph of a randomly frozen single nano / micro rod prepared in Example 6 mixed with a carrier to form a porous structure.

Referring to FIG. 8, when the length of the single nano / micro rods cut by frozen cutting is much longer than 1000 μm, it is shown that the nano / micro rods are amorphous entangled to form a porous structure.

FIG. 9 is a micrograph of a single nano / micro rod randomly frozen in Example 6 mixed with a carrier. FIG.

When a randomly frozen nano / micro-rod has a length of about 100 μm, it maintains the nano / micro-rod shape before mixing with the carrier.

That is, when the length of the single nano / micro fiber is as short as 100 μm, the shape is close to the linear shape similar to the linear structure before mixing with the carrier.

Example 7: Injection injected with a mixture of a single fiber prepared by PCL and a carrier (hyaluronic acid)

The nano / micro rod of the nano / micro rod of 26 mm in length prepared in Example 1 was mixed with 20 mg / ml of hyaluronic acid (Wako, molecular weight: 1,500,000) aqueous solution and then a 23 G needle tip And observed the shape of nano / micro-rods.

 The 26 mm length of the polycaprolactone nano / micro rods prepared in Example 7 formed a three-dimensional structure to form a porous network, and a single nano / micro rod was entangled amorphously to form a porous structure. This is similar to the shape of the injection injecting agent prepared by mixing the carrier (hyaluronic acid) of the nano / micro rod prepared in Example 6 and having a length of 25 mm.

Microscopic observation

The microscope glass, which was collected on the microscope glass, was immersed in distilled water or ethanol. After the sonicator was mixed with the freeze-cut nano / micro rod and carrier, the 23G needle tip The structures of the nano / micro rods and freeze-cut nano / micro rods after passing through the LV-10 microscope (Nikon, Tokyo, Japan) and NIS-Elements Documentation Version 4.00 (Nikon, Tokyo, Japan) And analyzed. We also confirmed the structure of nano / micro rods through a confocal microsphere.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the inventions. Will be clear to those who have knowledge of.

Claims (9)

An electrospinning step of electrospinning using a biodegradable polymer;
A fiber collecting step of collecting the electrospun fiber to a collector;
A cutting step of cutting the collected fibers through a cutting means to a predetermined length; And
And a separating step of separating the cut fibers from the cutting means,
Wherein the cutting is performed by increasing the length to 10 to 100 mm in the cutting step so as to cut the nano / micro rod.
The method according to claim 1,
Wherein the nano / micro rod cut after the cutting step further comprises a freezing step of freezing in the liquefied nitrogen and cutting it to a length of 100 m to 100 mm.
The method according to claim 1,
The biodegradable polymer is selected from the group consisting of polycaprolactone (PCL Mn = 80000, 60000, 45000), poly (L-lactic acid) (PLLA), poly (D, L- , Poly (lactic-glycolic acid) (PLGA), poly methyl metaacrylate, poly (hydroxyalkanoate), polydioxanone (PDS), polytrimethylenecarbonate, hydroxyapatite Wherein the compound is at least one compound selected from the group consisting of hydroxyapatite, fibril, alginate and calcium triphosphate.
The method according to claim 1,
Wherein the biodegradable polymer is a mixture of a linear polymer, a copolymer, a terpolymer, or another kind of homo / co / ter polymer. Based nano / micro rod.
The method according to claim 1,
Wherein the collector causes the radiated fibers to emit in a side-by-side fashion without overlapping each other, wherein the fibers are attached to two points of the collector.
6. The method of claim 5,
Wherein the rod is in the form of a bar having a U-shape or a spaced apart shape.
The method according to claim 1,
The cutting means is a solid material which can cut and cut the spun fibers,
So that the fibers can be cut at a position near the point where they are attached to the collector.
The method according to claim 1,
A nano / micro rod prepared in any one of claims 1 to 7 is mixed with a carrier and injected into the injection injecting agent so that the carrier can be injected with hyaluronic acid, carboxymethyl cellulose, Wherein at least one selected from the group consisting of collagen, alginic acid, gelatin, elastin, saline, and distilled water is used.
The method according to claim 1,
Wherein the nano / micro rod is available as an implant, a filler, and a scaffold.

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