KR102480105B1 - 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 electrospun fiber-based nano/micro rods and an injectable agent using the same, comprising: an electrospinning step of performing electrospinning using a biodegradable polymer; A fiber collection step of collecting the electrospun fibers in a collector; A cutting step of cutting the collected fibers to a predetermined length through a cutting means; And a separation step of separating the cut fiber from the cutting means, wherein in the cutting step, the length is adjustable from 10 to 100 mm and cut, characterized in that the electrospun fiber-based nano/micro rod manufacturing method and using the same Injectables are provided.

Description

Methods of Fabrication of Nano/microrod based on aligned electrospun fibers and its application of injectable nano/microrod system}

The present invention relates to a method for manufacturing electrospun fiber-based nano/microrods and an injectable preparation prepared therefrom, and more particularly, to an electrospinning device and a homemade collector using various biodegradable polymers with strong ductility, including polycaprolactone. It relates to a method for preparing a single nano/micro rod after producing aligned electrospun fibers using the same, and an injectable preparation in which the nano/micro rod is mixed with a carrier such as hyaluronic acid.

Conventionally, polycaprolactone (PCL), which has been used for decades as a medical polymer material such as a drug release control agent and surgical suture, helps collagen synthesis, and secures stability with FDA and CE approval. In order to manufacture an injectable injectable Looking at Patent Application No. 10-2015-0094455, polycaprolactone raw material was prepared using a cryogenic mill method, hyaluronic acid was diluted with 94 cc of distilled water, It is a composition characterized in that it is prepared by mixing 5% of polycaprolactone microspheres so that filler X for skin tissue restoration can be used for skin restoration. It imitates cryogenic mill processing and applied for a domestic patent by changing the gel carrier from Ellanse's carboxymethylcelluose (CMC) component to hyaluronic acid. The cryomilled polycaprolactone microspheres, the main ingredient of Ellanse and Filler X, produce collagen (Type I, Type III) responsible for elasticity and regeneration in their own skin, and are naturally produced over time. After the filler procedure, the volume-filled part becomes softer, and the effect lasts for more than 2 years after the initial injection, and then it is decomposed into water and carbon dioxide by hydrolysis, and it is completely decomposed, absorbed, and discharged with almost no residual rate.

However, it is known that the biodegradability of polycaprolactone is determined not by the form of polycaprolactone but by its molecular weight. When the molecular weight of polycaprolactone is Mn=80000, 60000, or 40000, its half-life is 2 years, 1 year, or 6 months. In the case of nano/microstructures prepared using polycaprolactone of the same molecular weight, the half-life is determined by the molecular weight, not the shape. If the molecular weight is the same, the half-life is also the same, but the surface area is larger than that of microspheres, and foreign body sensation when injected into the human body. There is a need for a polycaprolactone nano/micro rod structure that is less affected by gravity and less affected by gravity.

In addition, Korean Patent Application No. 2010-7004604 uses a mixed solution having a viscosity ranging from 1 to about 400,000 cP with solubilized polycaprolactone and a surfactant to prepare injectable polycaprolactone microspheres. After preparing polycaprolactone microparticles, a biodegradable injectable gel containing a carrier and an active ingredient is prepared, and the prepared injectable gel is used for implants, fillers and cosmetics (cosmetic) It is being developed for the use of gel. and slow with excellent properties such as flow properties due to essentially spherical microspheres, which can avoid aggregation, neddle clogging and noddule forming upon injection. Resorbable, biodegradable medical implants were required, and polycaprolactone microspheres using surfactants were developed. However, as claimed in the above patent, spherical microspheres are essential for preparing an injectable gel, but Patent Application No. 10-2017-7007215 and paper Subramanian et. al. 2015 Materials Science and Engineering C, 51, 16-17.

Meanwhile, looking at Korean Patent Application No. 2017-7007215, it was claimed that an injectable scaffolder complex containing hyaluronic acid and polycaprolactone nanostructures could be prepared and applied to soft tissue. The nanostructure was prepared by mixing polyethylene glycol diacrylate (PEG-DA) and thiolated hyaluronic acid (HA-SH) with a fibrous nanorod conjugated with maleimide (MAL). A hydrogel nanostructure was prepared by reacting the thiol groups of hyaluronic acid with diacryl groups at the ends of maleimide or polyethylene glycol fixed to PCL nanorods. In the process, the random mesh prepared using electrospinning is attached to the mesh surface through a multi-step process with maleimide groups. In short, the fiber is plasma treated to have functional groups on the fiber surface, conjugated acrylic acid through UV photopolymerization initiation, reacted with EDC and diazimine to form primary amine, and then reacted with SMCC to form maleimide. attach a group Then, it reacts with thiol groups in hyaluronic acid to form nanostructures. In this process, the functionalized fibrous mesh was immersed in liquid nitrogen and cut into 5x5 mm, or pulverized for 20 minutes using a mortar and pestle. In addition, a cryogenic mill (Freeaer/Mill 6770, SPEX SamplePrep, Metuchen, NJ) was used to prepare fiber fragments in which polyacrylic acid (PAA) was immobilized.

On the other hand, in the paper Knotek et al 2012 Materials Science and Engineering C 32, 1366-1374, various types of particles, fragments, and lumps were obtained by using cryomilling with liquid nitrogen after spinning using PCL (Mn = 40000) etc. were manufactured. In the case of fiber particles, the length was 300-1000μm and the width was about 5-50μm, the typical size of the fiber fragment was about 50μm and the maximum length was 300μm, and the size of the agglomerate with internal fibrous structure was 10-100μm and the internal fibrous structure was The size of the missing agglomerates ranged from 50 to 300 μm. In addition, the size of the thin plate was 30-40 μm and the thickness was less than 1 μm, and the nanoparticles were 100-150 nm in diameter and 40 μm in length. Nano/microfibers of various shapes and sizes are prepared by cryomiling electrospun fibers, but the disadvantage is that nano/microfibers of a single shape or size cannot be manufactured.

In addition, looking at Korean Patent Application No. 2014-0117060, electrospun fibers were prepared using PLLA (poly L-lactide) and the electrospun fibers were cut into small fragments, which were then mixed with 10% by weight of hexamethylenediamine (hexamethylenediamine). , HMDA) was added to dissolved isopropyl alcohol (IPA) and fragmented by vigorous mixing at 200 rpm for 30 minutes in a shaking incubator (SI-600R, Jeio Tech, Korea) at 37 ° C. The length of the prepared fibrous particles varied from about 10 to 80 μm (average length: 28.9 μm), and the fiber diameter maintained almost the original fiber diameter due to the relatively short aminolysis time. Also thesis Kim. et. al. 2008 Macromolecule Rapid Communication 29, 1231-1236, various periodic lengths (average length: 1.2 - 13.8 μm) due to the easy fracture of amorphous regions between lamellar crystalline domains under shear-stress. ) The nanorods were prepared by a chemical method such as aminolysis of a PLLA network having.

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, an object of the present invention is to manufacture nano/micro rods whose length can be controlled using PCL and various biopolymers.

Another object of the present invention is to develop nano/micro rods in the form of nano/micro rods that can be injected by mixing them with a carrier such as hyaluronic acid.

In order to achieve the above object, the present invention provides an electrospinning step of performing electrospinning using a biodegradable polymer; A fiber collection step of collecting the electrospun fibers in a collector; A cutting step of cutting the collected fibers to a predetermined length through a cutting means; And a separation step of separating the cut fibers from the cutting means, wherein the cutting step stretches the collected fibers to 10 to 100 mm through the cutting means, adjusts the length, and then cuts them. A method for manufacturing a microrod is provided.

In addition, according to the present invention, the nano / micro rods cut after the cutting step are frozen in liquid nitrogen and then electrospun fiber-based nano / micro rods further comprising a freeze cutting step to cut them to a length of 100 μm to 100 mm Provides a manufacturing method of.

In addition, according to the present invention, the biodegradable polymer is polycaprolactone (PCL Mn = 80000, 60000, 45000), poly (L-lactic acid) (PLLA), poly (D, L-lactic acid) PDLLA), poly Composed of (glycolic acid) (PGA), poly(lactic-glycolic acid) (PLGA), (poly(hydroxyalkanoate), polydioxanone (PDS), polytrimethyllinecarbonate, and alginate. It provides a method for producing an electrospun fiber-based nano/microrod, characterized in that it is at least one compound in the group.

In addition, according to the present invention, the biodegradable polymer is a linear polymer, a copolymer, a terpolymer, and a mixture of at least one of a homopolymer, characterized in that the electrospun fiber-based nano / micro A method for manufacturing a rod is provided.

In addition, according to the present invention, the collector is spaced apart from each other and includes a first bar and a second bar having a length in a direction perpendicular to the separation direction, both ends of the fiber are attached to the first bar and the second bar, respectively, It provides a method for manufacturing an electrospun fiber-based nano/micro rod, characterized in that the first bar and a plurality of fibers spun along the longitudinal direction of the first bar are arranged.

In addition, according to the present invention, there is provided a method for manufacturing an electrospun fiber-based nano/micro rod, characterized in that it is in the form of a U-shape or two spaced apart bars.

In addition, according to the present invention, the cutting means is a solid material that can be cut by stretching the spun fiber, and the electrospun fiber-based nano / A method for manufacturing a microrod is provided.

In addition, according to the present invention, as an injectable preparation formed by mixing the nano/microrods prepared by the above manufacturing method with a carrier to enable injection injection, the carrier is hyaluronic acid, carboxymethylcellulose ( carboxymethyl cellulose), collagen, alginic acid, gelatin, elastin, saline, and distilled water.

In addition, according to the present invention, the nano/micro rod provides an injection injectable that can be used as any one of an implant, a filler, and a cell scaffold.

The manufacturing method of electrospun fiber-based nano/microrods according to the present invention and the injection prepared therefrom can easily manufacture nano/microrods from aligned nanofibers made of highly ductile biomaterials such as polycaprolactone. there is.

The length of the nano/microrods manufactured by the method for manufacturing electrospun fiber-based nano/microrods according to the present invention can be adjusted to 100 μm to 10 cm.

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

The manufacturing method of electrospun fiber-based nano/microrods according to the present invention and the injection preparation containing nano/microrods prepared therefrom can be applied as cell scaffolds, fillers, implants, and the like.

1 schematically shows a manufacturing process diagram of electrospun fiber-based nano/microrods according to an embodiment of the present invention.
FIG. 2 schematically shows collecting and cutting fibers spun in the method for manufacturing electrospun fiber-based nano/microrods according to an embodiment of the present invention.
3 is a photomicrograph of nano/micro rods on a glass cutting means having a width of 26 mm in Example 1 of the present invention.
4 is a photomicrograph taken on glass after separating nano/micro rods with an ethanol solution using a sonicator in Example 1 of the present invention.
5 is a photomicrograph showing a state in Example 3 of immersing the nano/micro rod in liquid nitrogen and then freeze-cutting it once with a cutter.
6 is a photomicrograph showing a state in Example 3 of randomly freeze-cutting with a cutter after immersing nano/micro rods in liquid nitrogen.
7 is a photomicrograph of an injectable preparation in Example 6 in which a porous network is formed in a three-dimensional structure by mixing with a carrier (hyaluronic acid) of freeze-cut nano/microrods having a length of 25 mm.
8 is a photomicrograph of randomly freeze-cutting single nano/micro rods prepared in Example 6 mixed with a carrier to form a porous structure.
9 is a photomicrograph of randomly freeze-cutting single nano/micro rods mixed with a carrier in Example 6.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings. First of all, it should be noted that in the drawings, the same components or parts are denoted by the same reference numerals as much as possible. In describing the present invention, detailed descriptions of related known functions or configurations are omitted in order not to obscure the gist of the present invention.

As used herein, the terms about, substantially, etc., of degree, are used at or close to the value when manufacturing and material tolerances inherent in the referenced meaning are given, and are used in an accurate or Absolute numbers are used to prevent exploitation by unscrupulous infringers of the stated disclosure.

The present invention relates to a method for manufacturing electrospun fiber-based nano/micro rods and an injectable agent using the same, comprising: an electrospinning step of performing electrospinning using a biodegradable polymer; A fiber collection step of collecting the electrospun fibers in a collector; A cutting step of cutting the collected fibers to a predetermined length through a cutting means; And a separation step of separating the cut fiber from the cutting means, characterized in that it is a nano/micro rod manufactured by cutting by stretching the length to be adjustable from 10 to 100 mm in the cutting step, which can be used for injection. there is.

1 schematically shows a manufacturing process diagram of electrospun fiber-based nano/microrods according to an embodiment of the present invention.

FIG. 2 schematically shows collecting and cutting fibers spun in the method for manufacturing electrospun fiber-based nano/microrods according to an embodiment of the present invention.

The present invention consists of an electrospinning step, a collection step, a cutting step and a separation step, and additionally includes a freeze cutting step after the cutting step.

In the electrospinning step, biodegradable polymer fibers are spun using an electrospinning device.

The electrospinning apparatus uses a generally used one, and the electrospinning apparatus used is not particularly limited.

After putting a biodegradable polymer and a solvent in an electrospinning device to make a solution state, it is spun.

Here, the biodegradable polymer is polycaprolactone (PCL), poly(L-lactic acid) (PLLA), poly(D,L-lactic acid) PDLLA), poly(glycolic acid) (PGA), poly(lactic-glycolic acid) ) (PLGA), (poly(hydroxyalkanoate), polydioxanone (PDS), polytrimethylline carbonate, alginate, and the like.

In addition, the biodegradable polymer may be a mixture of at least one of a linear polymer, a copolymer, a terpolymer, and a homopolymer.

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

Nano or micro rods can be manufactured through electrospinning, which is achieved by adjusting the diameter of a needle tip used when spinning in an electrospinning device or adjusting the distance between the needle tip and a collector that collects fibers during spinning to produce hundreds of nanometer rods. Arranged nanofiber diameters from meters to several micrometers can be produced.

In the collecting step of the present invention, fibers discharged through electrospinning are collected so that the fibers are spun parallel to the collector.

The collector may have a U shape or a shape of two bars spaced apart from each other. In the two spaced apart bars, the two bars may or may not be parallel. The collector includes a first bar and a second bar spaced apart from each other and having a length in a direction perpendicular to the distanced direction, and both ends of the fiber are attached to the first bar and the second bar, respectively, so that the first bar and the first bar A plurality of fibers spun along the length of the bar may be arranged.

The collector allows the spun fibers to be spun side by side without overlapping each other, and the fibers are attached to two points of the collector.

The collector may be 10 to 100 mm in a U-shape with an upper and lower interval and an interval between the two spaced apart bars. The fibers collected through this can be cut into a certain size during subsequent cutting.

Referring to (a) of FIG. 2, fibers are spun side by side so as to span the upper and lower sides of the U-shaped collector. The spun fibers may be spun so as not to overlap each other and to be arranged side by side so as not to stick to each other.

After the collecting step, a cutting step is performed, in which the spun fibers are cut using a cutting means.

In the cutting step, the fiber spun through the cutting means may be stretched and cut from the collector. (See Fig. 2 (b))

The cutting means is a solid material capable of stretching and cutting the spun fibers, and allows the fibers to be cut at a position near the point where the fibers are attached to the collector.

In addition, the cutting means is not particularly limited in shape, form, and material, such as glass, U-shaped stainless steel, wire, plastic material, rectangular stainless steel, wire, plastic material, etc., and the inside of the width of the collector is cut. You should be able to do it.

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. This is carried out by soaking in a liquid substance such as ethanol.

In addition, the cut fibers can be separated from the cutting means by flowing a liquid such as distilled water, ethanol, or methanol instead of the sonicator. A solution such as ethanol and distilled water containing the separated fibers was naturally dried for 2 days or lyophilized, and then mixed with a carrier such as hyaluronic acid to make an injection preparation.

In addition, the present invention may further proceed with the cryocutting step after the cutting step.

Before separating the cut fibers from the cutting means, they were sufficiently immersed in liquid nitrogen and frozen-cut using a cutter. Alternatively, the cutting means with the cut fibers was immersed in ethanol or distilled water, poured with liquid nitrogen sufficiently, frozen, and then cut using a cutter.

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

In addition, in the present invention, the nano/micro rods produced through the electrospinning, collection, cutting, and separating steps or the nano/micro rods produced by adding a cryocutting step after the cutting step can be used as an injection injection agent.

An injectable injectable preparation for injection can be prepared by mixing the nano/microrod with a carrier. The carrier includes hyaluronic acid, carboxymethyl cellulose, collagen, and alginic acid At least one of alginic acid, gelatin, elastin, saline, and distilled water may be used.

In addition, the nano/micro rods can be used as an injection injection agent that can be used as any one of a plant, a filler, and a cell scaffold.

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

Example 1

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

Fibers aligned in the U-shaped electrospinning collector used glass as a cutting means so that the fiber length was 10 to 76 mm. Nano/micro rods can be cut by stretching and breaking the aligned nano/micro fibers.

In order to make nano/microrods of a desired length, the electrospun fibers were cut to a desired length by adjusting/processing the width of a glass microscope slide. Thereafter, the glass with the cut fibers was immersed in an ethanol solution, and then the nano/micro rods were separated from the glass using a sonicator for about 30 seconds, and the ethanol was completely dried to prepare the nano/micro rods.

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

4 is a photomicrograph taken on glass after separating nano/micro rods with an ethanol solution using a sonicator in Example 1 of the present invention.

Referring to FIG. 3 , when the fiber spun to the collector is stretched and cut through the glass, which is a cutting means, it can be confirmed that nano/micro rods, which are fibers spun on the glass, are present. Through this, it can be seen that the fiber can be stretched and cut with a cutting means such as glass.

Referring to FIG. 4 , after separating the nano/micro rods from the glass with an ethanol solution using a sonicator, it is shown that the nano/micro rods do not exist on the glass.

Example 2

Carried out in the same way as in Example 1,

The fiber in the collector was cut using a U-shaped cutting device as a cutting device, and nano/micro rods were separated into ethanol from the U-shaped cutting device.

Example 3

Carried out in the same way as in Example 1,

The stretched nano/micro rods collected on a microscope slide glass having a width of 26 mm were immersed in liquid nitrogen and freeze-cut with a cutter. Then, after immersing the glass with the cut fibers in the ethanol solution, use a sonicator for about 30 seconds or pour a solution such as ethanol over the cut glass with the nano/micro rods to separate the glass and the nano/micro rods, and then remove the ethanol. Completely dried to prepare nano/micro rods.

5 is a photomicrograph showing a state in Example 3 of immersing the nano/micro rod in liquid nitrogen and then freeze-cutting it once with a cutter.

6 is a photomicrograph showing a state in Example 3 of randomly freeze-cutting with a cutter after immersing nano/micro rods in liquid nitrogen.

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 cryo-cut nano/micro rod was 25 mm.

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

Example 4

Conducted in the same manner as in Example 1, but

It was prepared by freeze-cutting both ends of a stretched nano/micro rod having a length of 76 mm.

As in Example 4, the length of the freeze-cut nano/micro rod was 75 mm. Therefore, it was confirmed that the length of the freeze-cut nano/micro rods can be up to about 100 μm-75 mm.

Example 5

Carried out in the same way as in Example 1,

After drying the ethanol completely, pipetting the stretched nano/micro rods using primary distilled water or ethanol, and then sufficiently cooling the distilled water or ethanol containing the nano/micro rods in liquid nitrogen using liquid nitrogen, and using a cutter. After being randomly cut, the length of the freeze-cut nano/microrods was about 100-1000 μm.

Example 6: Injectable formulation in which a single fiber made of PCL and a carrier (hyaluronic acid) are mixed

The nano/microrod prepared in Example 3 was mixed with a 20mg/ml aqueous solution of hyaluronic acid (Wako, molecular weight: 1,500,000) and the nano/microrod of 25 mm in length was mixed with a 23G needle tip. After passing through, nano/microrods were observed.

7 is a photomicrograph of an injectable preparation in Example 6 in which a porous network is formed in a three-dimensional structure by mixing with a carrier (hyaluronic acid) of freeze-cut nano/microrods having a length of 25 mm.

Referring to FIG. 7 , nano/microrods with a length of 25 mm form a three-dimensional network structure even after being mixed with a carrier and passing 23G through a needle tip. In the case of nano/micro rods with a length of 25 mm, the nano/micro rods formed a three-dimensional structure forming a porous network.

FIG. 8 is a photomicrograph of randomly freeze-cutting single nano/micro rods prepared in Example 6 mixed with a carrier to form a porous structure.

Referring to FIG. 8 , when the length of a single cryo-cut nano/micro rod is much longer than 1000 μm, it is shown that the nano/micro rods are amorphously entangled to form a porous structure.

9 is a photomicrograph of randomly freeze-cutting single nano/micro rods mixed with a carrier in Example 6.

When randomly freeze-cutting nano/micro rods have a length of about 100 μm, they maintain the nano/micro rod shape before mixing with the carrier.

That is, when the length of a single nano/microfiber was as short as 100 μm, it showed a close-to-linear shape similar to the linear structure before mixing with the carrier.

Example 7: Injectable formulation in which a single fiber made of PCL and a carrier (hyaluronic acid) are mixed

After mixing the nano/micro rods prepared in Example 1 with a 26 mm long polycaprolactone nano/micro rods with a 20 mg/ml aqueous solution of hyaluronic acid (Wako, molecular weight: 1,500,000), a 23 G needle tip was used. The morphology of the nano/microrods was observed.

The polycaprolactone nano/microrods having a length of 26 mm prepared in Example 7 formed a three-dimensional structure forming a porous network, and single nano/microrods were amorphously entangled to form a porous structure. This is similar to the form of the injection prepared in Example 6, in which a carrier (hyaluronic acid) of cryo-cut nano/micro rods having a length of 25 mm is mixed.

microscope observation

The nano/micro rods stretched and broken on the microscope glass used in the example, and the microscope glass in which the nano/micro rods were collected were immersed in distilled water or ethanol, sonicated, and then mixed with the freeze-cut nano/micro rods and carriers, and then 23G needle tip The structures of the nano/microrods stretched and cut after passing through and freeze-cut nano/microrods were analyzed using an LV-10 microscope (Nikon, Tokyo, Japan) and NIS-Elements Documentation Version 4.00 (Nikon, Tokyo, Japan). Acquired and analyzed. Also, the structure of the nano/microrods was confirmed through a confocal microsphere.

The present invention described above is not limited by the foregoing embodiments and the accompanying drawings, and various substitutions, modifications, and changes are possible within a range that does not deviate from the technical spirit of the present invention. It will be clear to those who have knowledge of

Claims (9)

Electrospinning step of performing electrospinning using a biodegradable polymer;
A fiber collection step of collecting the electrospun fibers in a collector;
A cutting step of cutting the collected fibers to a predetermined length through a cutting means; and
Including a separation step of separating the cut fibers from the cutting means,
The cutting step is a method of manufacturing an electrospun fiber-based nano/microrod, characterized in that by stretching the collected fibers to 10 to 100 mm through the cutting means, adjusting the length, and then cutting them.
According to claim 1,
After the cutting step, the cut nano / micro rod is frozen in liquid nitrogen and then further comprising a freeze cutting step to cut it to a length of 100 μm to 100 mm Electrospun fiber-based nano / micro rod manufacturing method.
According to claim 1,
The biodegradable polymer is polycaprolactone (PCL), poly(L-lactic acid) (PLLA), poly(D,L-lactic acid) PDLLA), poly(glycolic acid) (PGA), poly(lactic-glycolic acid) ) (PLGA), (poly (hydroxyalkanoate), polydioxanone (PDS), polytrimethylline carbonate, based on electrospun fibers characterized in that at least one compound from the group consisting of alginate Manufacturing method of nano/micro rods.
According to claim 1,
Wherein the biodegradable polymer is a mixture of at least one of a linear polymer, a copolymer, a terpolymer, and a homopolymer.
According to claim 1,
The collector includes a first bar and a second bar spaced apart from each other and having a length in a direction perpendicular to the distanced direction, and both ends of the fiber are attached to the first bar and the second bar, respectively, so that the first bar and the first bar A method of manufacturing an electrospun fiber-based nano/microrod, characterized in that a plurality of fibers spun along the longitudinal direction of the bar are arranged.
delete According to claim 1,
The cutting means is a solid material that can stretch and cut the spun fibers,
A method of manufacturing an electrospun fiber-based nano/microrod, characterized in that the fiber can be cut at a position near the point attached to the collector.
An injection injection prepared by mixing the nano/microrods prepared by the method of manufacturing electrospun fiber-based nano/microrods according to any one of claims 1 to 5 with a carrier to enable injection injection,
The carrier is characterized by using at least one of hyaluronic acid, carboxymethyl cellulose, collagen, alginic acid, gelatin, elastin, saline, and distilled water. Injection infusion made by.
According to claim 8,
The nano/microrod is an injection injectable that can be used as any one of a plant, a filler, and a cell scaffold.

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