KR20200038374A - Micro-patterned conductive hydrogel hybrid system scaffold and preparing method thereof - Google Patents

Abstract

The present invention relates to a scaffold capable of acting more effectively on cell-to-cell communication and cell responses by providing a micro-pattern on the surface of a hydrogel using photolithography, and polymerizing a conductive polymer into a semi-interpenetrating structure, thereby simultaneously imparting a physical stimulation and an electrical stimulation; and to a manufacturing method of the scaffold.

Description

Micro-patterned conductive hydrogel hybrid system scaffold and preparing method thereof

The present invention relates to a micro-patterned conductive hydrogel hybrid system scaffold and a method of manufacturing the scaffold.

Tissue engineering is a study aimed at maintaining, restoring or improving the function of a living body by culturing tissues in vitro and then transplanting them into the body to regenerate and treat tissues. Tissue engineering requires a scaffold that is an artificial extracellular matrix mimetic to build tissues and control cellular functions after culturing cells in vitro.

By the interaction of the extracellular matrix with the cells, the biological tissue can maintain its shape and function. Scaffolds mimic these extracellular matrix in vitro. Typical scaffolds are nanofibers, porous sponges, and hydrogels. The scaffold must have good biocompatibility, no cytotoxicity, and mechanical strength and physical properties similar to those of the extracellular matrix.

Myocardial cells, nerve cells, and muscle cells transmit signals through an electrical method, which enables communication between cells and cells, and also has a positive effect on cell-cell interactions, where cells differentiate into tissues. Helps to promote the formation of new organizations. On the other hand, myocardial, nerve, and muscle cells are cells that are difficult to self-regenerate once damaged, and it takes a long time to recover to a normal state, and mostly exists as a permanently damaged state that cannot be recovered, resulting in increased mortality due to complications. Trend. Therefore, a histotechnical approach is essential to regenerate these cells, and it is necessary to impart electrical conductivity to the scaffold so that these cells can correctly construct tissue. In recent biomedical research, conductive hydrogels that combine electrical functional groups with hydrated three-dimensional structures have attracted great interest.

There are two main methods of imparting conductivity to hydrogels. The first is a method of first producing a hydrogel with a hybrid system and then polymerizing the conductive polymer inside the hydrogel. The second method is to prepare a hydrogel having a single conductive polymer as a continuous phase by providing a functional group capable of self-assembling the conductive polymer or crosslinking in three dimensions.

When the various surfaces of the biomaterial are adjusted on a micro- or nano-scale, cell functions such as morphology, adhesion, and movement of cells can be controlled, and the behavior of these cells can positively influence proliferation and differentiation. The influence of the topological cue may vary depending on the type of cell, the shape and the size of the phase shape, and the more imitated the phase is, the more the trait becomes similar to the cells in the body. With the advent of micro- and nano-fabrication, the effects of various phases on cell shape, proliferation and differentiation have also been studied in cell culture platforms. Recently, physical variables such as morphology and intensity as well as biochemical signals have emerged as important elements of the scaffold. Wang et al. Showed that the micropattern inhibits the proliferation of skeletal muscle cells and improves differentiation capacity. Since the nanopattern is much smaller than the cell size, there is a disadvantage that it is impossible to control the position of the cell, so a micropattern is suitable to accurately control the position of the cell.

Fu et al. Studied the effect of spreading and attaching osteosarcoma cells according to the height and distance of the micropattern on PDMS and showed that the cells are arranged along the micropattern direction when the distance of the groove corresponds to the spread cell size. . However, since this pattern traps the cells in a geometric structure, the separated micro-pattern makes the interface between the individual cells unable to contact each other, weakening the cell-cell interaction.

 Modulation of Alignment and Differentiation of Skeletal Myoblasts by Submicron Ridges / Grooves Surface Structure, Biotechnology and Bioengineering, 106: 285-294 (2010).  Fu G, Soboyejo WO (2009) Cell / surface interactions of human osteo-sarcoma (HOS) cells and micro-patterned polydimelthylsiloxane (PDMS) surfaces, Materials Science & Engineering C-Materials for Biological Applications 29: 2011-2018.

The present invention is to provide a micro patterned conductive hydrogel hybrid system scaffold and a method of manufacturing the scaffold.

In addition, according to the present invention, physical stimulation and electrical stimulation can be simultaneously imparted by imparting a micro pattern to the surface of a hydrogel using photolithography and polymerizing a conductive polymer with a semi-interpenetration network. , To provide a scaffold that can act more effectively on cell-to-cell communication and cell response.

In order to solve the above problems,

The present invention in one embodiment,

Hydrogel is formed on the surface of the micro-pattern repeating protrusions and recesses; And a conductive polymer formed on the micro pattern surface of the hydrogel, wherein the conductive polymer provides a scaffold that is a semi-interpenetration network.

In addition, the present invention in one embodiment,

Provided is a method of manufacturing a scaffold comprising polymerizing an anti-penetrating structure conductive polymer on a hydrogel having a micro-pattern formed by reacting a hydrogel having a micro-pattern with repeated protrusions and recesses on the surface and a conductive polymer precursor solution. do.

The scaffold according to the present invention can easily provide a micro pattern on the surface of a hydrogel using photolithography or softlithography, and polymerizes a conductive polymer into a semi-interpenetration network. By doing so, it is possible to manufacture a conductive hydrogel hybrid system that exhibits unique characteristics by combining electrical functional groups with a three-dimensional hydrated hydrogel.

In addition, the scaffold according to the present invention, by modifying the surface of the hydrogel, which is unable to attach cells, allows biomaterials such as cells or proteins to adhere and grow well, and provides an extracellular matrix environment similar to that of the body in vitro. . In addition, in other areas without surface modification, disturbances of direct contact between proteins or cells can be minimized, and cells can be cultured in a desired shape through patterning, and cells can be cultured in an alignment arranged in one direction. In this case, the cell differentiation effect can be maximized to play a large role in building tissue. In particular, the polymer hydrogel is excellent in biocompatibility and can reduce the immune response, and has a porous structure, so that cells can metabolize and actively diffuse the gas or moisture generated by the cells, and the structure can contain drugs. It has the advantage that cells can mount and slowly release factors necessary for growth and differentiation.

Thus, the scaffold containing the micro-patterned conductive hydrogel according to the present invention is tissue engineering aimed at tissue regeneration, organ function recovery, and treatment by regularly culturing cells and conferring electrical functional groups necessary for cell-to-cell communication. And cell biology, and further, biosensors, drug delivery systems, and the like.

FIG. 1 sequentially illustrates a method of manufacturing the micro-patterned conductive hydrogel of the present invention, and sequentially shows a method of surface modification capable of fixing the RGD peptide to the micro-patterned conductive hydrogel of the present invention.
2 is a photograph of a conductive hydrogel made according to Examples 1 to 3 of the present invention.
3 is a scanning electron microscope (SEM) image of the same material as in FIG. 2.
Figure 4 is an image of culturing muscle cells C2C12 for 6 days using the conductive hydrogel having micro-patterns of the present invention as a scaffold.
Figure 5 shows the results of measuring the surface electrical conductivity of the micro-patterned conductive hydrogel surface of the present invention before and after surface modification.

The present invention can be variously modified and can have various embodiments, and specific embodiments will be illustrated in the drawings and described in detail in the detailed description.

However, this is not intended to limit the present invention to specific embodiments, and should be understood to include all modifications, equivalents, and substitutes included in the spirit and scope of the present invention.

In the present invention, terms such as “comprises” or “have” are intended to indicate that there are features, numbers, steps, operations, components, parts, or combinations thereof described in the specification, and one or more other features. It should be understood that the existence or addition possibilities of fields or numbers, steps, operations, components, parts or combinations thereof are not excluded in advance.

Hereinafter, the present invention will be described in detail.

Myocardial cells, nerve cells, and muscle cells transmit signals through an electrical method, which enables communication between cells and also positively affects the interaction between cells, whereby cells are differentiated into tissues. It helps and promotes the formation of new tissue. On the other hand, myocardial, nerve, and muscle cells are cells that are difficult to self-regenerate once damaged, and it takes a long time to recover to a normal state, and mostly exists as a permanently damaged state that cannot be recovered, resulting in increased mortality due to complications. Trend. Therefore, a histotechnical approach is essential to regenerate these cells, and it is necessary to impart electrical conductivity to the scaffold so that these cells can correctly construct tissue. In recent biomedical research, conductive hydrogels that combine electrical functional groups with hydrated three-dimensional structures have attracted great interest.

Accordingly, the present invention provides a micro pattern on the surface of a hydrogel using photolithography or softlithography, and physical and electrical stimulation by polymerizing a conductive polymer with a semi-interpenetration network. It can provide at the same time, and provides a scaffold that can act more effectively on cell-to-cell communication and cell response.

Specifically, the present invention is a hydrogel formed on the surface of the micro-pattern is repeated protrusions and recesses; And a conductive polymer formed on the micro pattern surface of the hydrogel, wherein the conductive polymer provides a scaffold that is a semi-interpenetration network.

The scaffold according to the present invention can easily provide a micro pattern on the surface of a hydrogel using photolithography, and polymerizes a conductive polymer into a semi-interpenetration network to 3D hydrated hydrogel. A conductive hydrogel hybrid system that exhibits unique properties can be prepared by combining electrical functional groups with.

In addition, the scaffold according to the present invention, by modifying the surface of the hydrogel, which is unable to attach cells, allows biomaterials such as cells or proteins to adhere and grow well, and provides an extracellular matrix environment similar to that of the body in vitro. . In addition, in other areas without surface modification, disturbance of direct contact between proteins or cells can be minimized, and cells can be cultured in a desired shape through patterning, and when cells are cultured in an alignment arranged in one direction. It can play a big role in building tissues by maximizing the differentiation effect of cells. In particular, the polymer hydrogel is excellent in biocompatibility and can reduce the immune response, and has a porous structure, so that cells can metabolize and actively diffuse the gas or moisture generated by the cells, and the structure can contain drugs. It has the advantage that cells can mount and slowly release factors necessary for growth and differentiation.

The conductive polymer material may be at least one selected from the group consisting of poly (3,4-ethylenedioxythiophene): polystyrenesulfonic acid, polypyrrole: polystyrenesulfonic acid and polythiophene: polystyrenesulfonic acid.

The ratio of the width of the protrusions and the width of the recesses (the width of the protrusions / the width of the recesses) in the micro pattern may be 1 to 3, and the width of the recesses may be 1 to 3 μm. For example, the ratio of the width of the protrusions and the width of the recesses of the micro pattern may be 1 to 3, 1 to 2.5, 1 to 2.0, 1.5 to 3.0, or 2.0 to 3.0, wherein the width of the recesses is 1 to 3 μm , 1 to 2.0 μm, or 1 to 1.5 μm, and the protrusion width may be 1 to 3 μm, 1.5 to 3 μm, or 2.0 to 3.0 μm.

The scaffold may be surface-modified with 5-azido-2-nitrobenzoic acid N-hydroxysuccinimide ester, and dimethyl as a solvent during the surface modification It may be to include formaldehyde (N, N-dimethylformaldehyde, DMF). In addition, the scaffold may be surface-modified using an amino acid sequence consisting of Gly-Arg-Gly-Asp-Ser (glycine-arginine-glycine-aspirate-serine, GRGDS). An NHS functional group may be imparted to the surface of the hydrogel having a micro pattern formed by the surface modification.

The 5-azido-2-nitrobenzoic acid N-hydroxysuccinimide ester used in the surface modification reaction has two different reactive active groups on each side, and when reacted with light on the scaffold surface, 5-azido- The phenyl azido group of 2-nitrobenzoic acid N-hydroxysuccinimide ester is formed of a highly reactive phenyl nitrene group, which serves to chemically fix the polymer surface. The N-hydroxysuccinimide ester group on the other side reacts with the primary amine group which is the NH ₂ (amino group) of the protein or amino acid sequence to be attached to form a covalent bond. Thus, the surface of the scaffold can be fixed on one side by using the 5-azido-2-nitrobenzoic acid N-hydroxysuccinimide ester, which is a bifunctional linker. On one side, it can be modified with proteins, amino acids, etc. that can fix the cells.

Hydrogels have the advantage of having a high moisture content, biocompatibility and hydrophilicity, being transparent, and having the advantage of easily controlling physical properties with a molecular weight, but they cannot use functional groups and cannot adhere to cells or proteins. As it has, it is limited to many bio-field applications such as biosensors, tissue engineering, and drug delivery devices. However, by attaching cells, proteins, etc. through surface modification according to the present invention, it can be used in various bio fields and overcome the limitations of hydrogels.

The scaffold may impart conductivity by polymerizing with a conductive polymer, and the electrical conductivity of the scaffold may be 0.001 to 0.020 S / cm. For example, the electrical conductivity of the scaffold may be 0.001 to 0.020 S / cm, 0.001 to 0.015 S / cm, 0.001 to 0.010 S / cm, or 0.010 to 0.020 S / cm.

The hydrogel is composed of a hydrophilic polymer in a three-dimensional network structure containing a large amount of water, for example, the hydrogel is polyethylene glycol (PEG), polyethylene oxide (PEO), polyhydroxyethyl methacrylate (PHEMA ), Polyacrylic acid (PAA), polyvinyl alcohol (PVA), poly (N-isopropylacrylamide) (PNIPAM), polyvinylpyrrolidone (PVP), polylactic acid (PLA), polyglycolic acid (PGA) and Polycaprolactone (PCL), collagen, gelatin, fibrin, hyaluronic acid, alginate, carrageenan, chitosan, hydroxyalkylcellulose, alkylcellulose, silicone, rubber, agar, carboxyvinyl copolymer, polydioxolane, polyacrylic acetate, poly Vinyl chloride, maleic anhydride / vinyl ether, or one or more hydrophilic polymers selected from the group consisting of copolymers or mixtures thereof. Since the hydrogel has an easily adjustable porous structure, it is possible to mount the drug on the hydrogel, and it is possible to control the time and rate of drug release by controlling the pore size. In addition, since it has a high moisture content, cells and biomaterials can be contained inside the hydrogel without damage, and it has a feature of having high biocompatibility due to physical and chemical similarities with the extracellular matrix.

The scaffold comprising the micro-patterned conductive hydrogel according to the present invention is tissue engineering and cells aimed at tissue regeneration and organ function recovery, treatment by regularly culturing cells and conferring electrical functional groups necessary for communication between cells and cells It can be used for biology, and it can be used for biosensors, drug delivery systems, etc.

In addition, the present invention is a scaffold comprising polymerizing an anti-penetrating structure conductive polymer on a hydrogel having a micro-pattern formed by reacting a hydrogel having a micro-pattern with repeated protrusions and recesses on the surface and a conductive polymer precursor solution. It provides a method of manufacturing.

A conductive polymer may be polymerized in the hydrogel having a micro pattern in which the protrusions and recesses are repeatedly formed on the surface, and the conductive polymer may be polymerized in the hydrogel in which the micro patterns are formed. A conductive hydrogel hybrid system can be prepared by combining an electrical functional group with a three-dimensional hydrated hydrogel.

Forming a micro pattern in which protrusions and recesses are repeated on the surface of the hydrogel may be patterned by photolithography or soft lithography.

For example, in the method of forming the micro pattern, a hydrogel precursor solution is placed on a micro patterned wafer and then irradiated with UV light to produce a hydrogel having a micro pattern, wherein the protrusions of the micro pattern are formed. The ratio of the width to the width of the recess (projection width / concave width) is 1 to 3, and the width of the recess may be 1 to 3 μm. For example, the ratio of the width of the protrusions and the width of the recesses of the micro pattern may be 1 to 3, 1 to 2.5, 1 to 2.0, 1.5 to 3.0, or 2.0 to 3.0, wherein the width of the recesses is 1 to 3 μm , 1 to 2.0 μm, or 1 to 1.5 μm, and the protrusion width may be 1 to 3 μm, 1.5 to 3 μm, or 2.0 to 3.0 μm. The ratio of the width of the protruding portion and the width of the concave portion of the micro pattern may be adjusted according to the size of the micro patterned wafer.

For example, as a method of forming a micro pattern, in addition to photolithography, electron beam lithography, two-photon polymerization, microcontact printing, etching, electrospinning, etc. are included. It can be used for the properties of the surface by adjusting its shape and dimension.

After polymerizing the conductive polymer on the hydrogel having the micro pattern, the NHS functional group may be introduced into the hydrogel polymerized with the conductive polymer and reacted with the RGD peptide solution to further modify the surface. The surface of the hydrogel, which is unable to adhere to the cell by surface modification, can be grown by being favored with a biomaterial such as a cell or protein, and can provide an extracellular matrix environment similar to the body in vitro.

Introducing the NHS functional group into the hydrogel polymerized with the conductive polymer, after applying the 5-azido-2-nitrobenzoic acid N-hydroxysuccinimide ester-containing solution on the hydrogel polymerized with the conductive polymer, The surface may be modified by irradiating UV light. In addition, introducing the NHS functional group into the hydrogel polymerized with a conductive polymer, Gly-Arg-Gly-Asp-Ser (glycine-arginine-glycine-aspirate-serine on the hydrogel polymerized with the conductive polymer), GRGDS) may be surface-modified using an amino acid sequence. When the surface is modified, it may be to include dimethylformaldehyde (N, N-dimethylformaldehyde, DMF) as a solvent.

Hydrogels have the advantage of having a high moisture content, biocompatibility and hydrophilicity, being transparent, and having the advantage of easily controlling physical properties with a molecular weight, but they cannot use functional groups and cannot adhere to cells or proteins. As it has, it is limited to many bio-field applications such as biosensors, tissue engineering, and drug delivery devices. However, by attaching cells, proteins, etc. through surface modification according to the present invention, it can be used in various bio fields and overcome the limitations of hydrogels.

Hereinafter, the present invention will be described in more detail through examples and the like according to the present invention, but the scope of the present invention is not limited by the examples given below.

Example

A schematic diagram of a method of manufacturing a scaffold according to the present invention is shown in FIG. 1, which was described in detail in Examples 1 to 4 below.

Example  One: Polyethylene glycol Diacrylate ( polyethylene glycol -diacrylate, PEG DA ) synthesis

In a three-necked flask, 10 g of polyethylene glycol (PEG) and 100 mL of tetrahydrofuran were added and dissolved in a constant temperature water bath at 50 ° C. After supplying nitrogen gas and refluxing, 4 mL of acrylyl chloride was added. The reaction was performed with stirring for 5 hours. After cooling to 4 ° C., the solvent was discarded and PEG DA solid was recovered.

Example  2: Patterned PEG _ PSS  Semi mutual penetration Polymer network Hydrogel  formation

3 g of PEG DA was mixed in 3 mL of deionized water, and then left at room temperature for 1 hour to dissolve completely. 300 μl of the initiator HOMPP was added to the dissolved PEG DA solution. 2 mL of a poly (4-styrenesulfonic acid) solution was added to the precursor solution and mixed. 0.5 mL of the prepared precursor solution was placed on a micro patterned wafer, and then UV light having a wavelength of 365 nm was output at 18 Wcm ^-2 . Irradiation was performed for 300 seconds The resulting PSS PEG hydrogel was patterned on the surface of the hydrogel in the shape of a micro-patterned wafer, and the PSS chain polymer was PEG 3D by removing the remaining monomers and initiators by maintaining it in ethanol for 2 days. A hydrogel encapsulated in a semi-penetrating polymer network form in a network structure was obtained.

Example  3: Hydrogel  Within PEDOT  polymerization

After maintaining the hydrogel of Example 2 in a solution of 1.8 mL of EDOT solution and 0.2 mL of 99.9% ethanol for 2 hours, the remaining EDOT solution was removed. 300 mg of iron-ρ-toluenesulfonate hexahydrate [Iron (III) -ρ-toluenesulfonate hexahydrate] was dissolved in 2 mL of 99.9% ethanol, and then 0.5 v / v% sulfuric acid solution was added. The hydrogel was immersed in the mixed solution, and the ultrasonic disperser was applied for 15 minutes to start. The polymerization was carried out for 4 days at room temperature and dark. After the polymerization was completed, the photoinitiator and the remaining monomer were washed with ethanol for 2 days.

The photo of the obtained hydrogel is shown in FIG. 2.

Example  4: micro Patterned  Conductive polymer Hydrogel Scaffolding Surface modification

4 mg of 5-azido-2-nitrobenzoic acid N-hydroxysuccinimide ester was dissolved in 1 mL of DMF. After covering the micro-patterned conductive polymer hydrogel scaffold with 100 μl of the solution, the solvent was dried in a fume hood. In order to chemically bond the phenyl azide functional group to the surface of the dried conductive hydrogel, UV light having a wavelength of 365 nm was irradiated with an output of 18 Wcm ^-2 for 300 seconds. The hydrogel was washed twice with DMF and then once with DPBS. To react the surface NHS functional group with the NH ₂ functional group of the RGD peptide, 100 µl of a solution of 1 mg of the RGD peptide dissolved in 1 mL of DPBS was placed on a washed conductive hydrogel and incubated at 37 ° C. for 24 hours.

Example  5: Patterned Scaffolding  Cell culture experiment

The scaffold was placed on a 48 well plate, washed with 70% ethanol and 95% ethanol, respectively, and sterilized with UV for 30 minutes. C2C12 myoblasts were cultured in a medium containing high-DMEM and FBS (10% w / v) in a 5% CO ₂ , 95% air, 37 ° C environment. When the cells occupied 70% in the polystyrene culture flask, the cells were detached with trypsin / EDTA. Cells were dispersed in the media at a concentration of 105 cells / mL, and then 100 μl was dropped on each scaffold. After the C2C12-dispensed scaffold was incubated in a 5% CO ₂ , 95% air, 37 ° C. environment for 1 hour so that the cells adhered well to the scaffold, 500 µl of media was placed in each well plate. Cell culture media was changed every 2 days. Cells attached to the hydrogel can be visualized with Live / Dead Viability, which is shown in FIG. 4.

Example  6: Conductivity measurement experiment

Using the patterned conductive hydrogel, electrical conductivity according to the presence or absence of surface modification was measured and compared. The surface-modified conductive hydrogel and the surface-modified conductive hydrogel were immersed in deionized water or Dulbecco's Phosphate-Buffered Saline (DPBS), respectively, and then swollen at room temperature for about 1 day. Each conductive hydrogel was analyzed for surface conductivity with a sheet resistance meter (4-point probe). After placing the conductive hydrogel on a 78 mm * 56 mm glass slide glass, place the sample on the probe stage. After setting the voltage and current automatically and setting the function to sheet, press the four probes to touch the conductive hydrogel surface. The resistance was measured 10 times for one scaffold, and the average value was used as the surface resistance. After measuring 4 scaffolds for each condition and substituting the measured value into the surface resistance formula, the resistance value was calculated, and the average value and the deviation were calculated to compare the electrical conductivity. The measurement results of this example are shown in FIG. 5.

Figure 5 shows the electrical conductivity of the CH scaffold swelling in deionized water (DI) and PBS solvent, the surface unmodified scaffold was highest at 0.0131 S / cm in DPBS, and 0.0021 S / cm in deionized water, The surface-modified scaffold was measured to be 0.0069 S / cm in DPBS and 0.0011 S / cm in deionized water, and it was confirmed that the conductivity slightly decreased after surface modification. Although the conductivity was slightly decreased after the surface modification, it was found that the scaffold according to this embodiment is suitable for electric signal transmission and close to the physiological environment.

Claims (10)

Hydrogel is formed on the surface of the micro-pattern repeating protrusions and recesses; And
Containing a conductive polymer formed on the micro-pattern surface of the hydrogel,
The conductive polymer is a scaffold that is a semi-interpenetration network.
According to claim 1,
The conductive polymer material is at least one scaffold selected from the group consisting of poly (3,4-ethylenedioxythiophene): polystyrenesulfonic acid, polypyrrole: polystyrenesulfonic acid and polythiophene: polystyrenesulfonic acid.
According to claim 1,
The ratio of the width of the protrusions and the width of the recesses in the micro pattern is 1 to 3,
The scaffold with a concave width of 1 to 3 μm.
According to claim 1,
The scaffold is a scaffold that is surface-modified with 5-azido-2-nitrobenzoic acid N-hydroxysuccinimide ester.
According to claim 1,
The scaffold has an electrical conductivity of 0.001 to 0.020 S / cm.
According to claim 1,
Hydrogels include polyethylene glycol, polyethylene oxide, polyhydroxyethyl methacrylate, polyacrylic acid, polyvinyl alcohol, poly (N-isopropylacrylamide), polyvinylpyrrolidone, polylactic acid, polyglycolic acid and polycaprolactone. , Collagen, gelatin, fibrin, hyaluronic acid, alginate, carrageenan, chitosan, hydroxyalkylcellulose, alkylcellulose, silicone, rubber, agar, carboxyvinyl copolymer, polydioxolane, polyacrylic acetate, polyvinyl chloride, maleic anhydride / A scaffold comprising one or more hydrophilic polymers selected from the group consisting of vinyl ethers or copolymers thereof or mixtures thereof.
A method of manufacturing a scaffold comprising polymerizing an anti-penetrating structure conductive polymer on a hydrogel formed with a micro-pattern by reacting a hydrogel having a micro-pattern on which the protrusions and recesses are repeated on the surface and a conductive polymer precursor solution.
The method of claim 7,
The method of manufacturing a scaffold is to form a micro pattern in which protrusions and recesses are repeated on the surface of a hydrogel by patterning by photolithography or soft lithography.
The method of claim 7,
After polymerizing the conductive polymer on the hydrogel having a micro pattern,
A method for producing a scaffold, further comprising modifying a surface by introducing an NHS functional group into a hydrogel polymerized with the conductive polymer and reacting with a RGD peptide solution.
The method of claim 9,
Introducing the NHS functional group into the hydrogel in which the conductive polymer is polymerized,
A method for producing a scaffold, which is irradiated with UV light after coating a solution containing 5-azido-2-nitrobenzoic acid N-hydroxysuccinimide ester on a hydrogel polymerized with the conductive polymer.

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