KR20130024726A - Biocompatible nano-fiber, manufacturing method for the same, and cell scaffolding material using the same - Google Patents

Abstract

PURPOSE: A nano fabric having bio-compatibility, a manufacturing method thereof and cell scaffolding material are provided to have excellent shape stability and mechanical strength by containing a copolymer of polyhedral oligosilsesquioxane, polyethylene glycol, and polycaprolactone. CONSTITUTION: A nano fabric having bio-capability comprises a copolymer of polyhedral oligosilsesquioxane, polyethylene glycol, and polycaprolactone. The polyhedral oligosilsesquioxane is denoted by chemical formula 1. In the chemical formula 1, R indicates an alkyl group, and R` indicates a functional group having a reactive group on the end.

Description

Biocompatible nano-fiber, manufacturing method for the same, and cell scaffolding material using the same

The present invention relates to nanofibers with biocompatibility, and more particularly to nanofibers useful as cell scaffold materials, methods of making and cell scaffold materials.

Polycaprolactone (PCL) is known as a semicrystalline polymer that has excellent mechanical strength and shape stability, and has superior biodegradability and biocompatibility compared with other polymers, and is degraded in vivo because of its slow degradation in vivo. It is promising as a cell scaffolding material to be used (for example, refer patent document 1 and 2).

International Publication No. 2006/135103 International Publication No. 2007/102606

However, since PCL exhibits strong hydrophobicity, when PCL is used as a cell scaffolding material, cells have a property of being hard to adhere to the PCL (inferior cell adhesion). Therefore, the emergence of new materials that are excellent in mechanical strength and shape stability, excellent in biodegradability and biocompatibility, slow in vivo degradation and better adhesion to cells than PCL like PCL. .

Accordingly, the present invention has been made in view of such a situation, and has excellent mechanical strength and shape stability, excellent biodegradability and biocompatibility, slow degradation in vivo, and excellent adhesion to cells. And a method for producing the same and a cell scaffolding material.

[1] The nanofibers of the present invention have a copolymer of polycaprolactone, polyethyleneglycol, and polyhedral oligosilsesquioxane.

[2] In the nanofibers of the present invention, the polyhedral oligosilsquioxane is preferably a polyhedral oligosilsquioxane represented by the following general formula (1).

(However, in formula (1), R represents an alkyl group, R 'represents a functional group having a reactive group at the terminal)

[3] In the nanofiber of the present invention, the number average molecular weight of the polyethylene glycol is preferably 3400 to 8000.

[4] In the nanofiber of the present invention, one produced by the electrospinning method is preferable.

[5] The method for producing nanofibers of the present invention comprises a mixing step of mixing a solution containing polycaprolactone, a solution containing a copolymer of polyethylene glycol and polyhedral oligosilsesquioxane, and an electrospinning method. It has a fiberizing process which obtains a nanofiber from the mixed solution obtained at the said mixing process by the above.

[6] In the method for producing nanofibers of the present invention, a copolymer synthesis step of obtaining a copolymer by urethane bonding polyethylene glycol and propyldimethylsilylcyclohexyl isocyanate-polyhedral oligosilsquioxane (Isocyanatopropyldimethylsilylcyclohexyl-polyhedral oligosilsesquioxane) before the mixing step It is preferable to have more.

[7] In the method for producing a nanofiber of the present invention, the polyhedral oligosilsquioxane is preferably a polyhedral oligosilsquioxane represented by the following formula (2).

(However, in formula (2), R represents an alkyl group, R 'represents a functional group having a reactive group at the terminal)

[8] In the method for producing a nanofiber of the present invention, the number average molecular weight of the polyethylene glycol is preferably 3400 to 8000.

[9] The cell scaffold material of the present invention comprises the nanofiber of the present invention.

According to the present invention, a nanofiber having excellent mechanical strength and shape stability, excellent biodegradability and biocompatibility, slow deterioration in vivo, and excellent adhesion to cells, a method for producing the same, and a cell scaffolding material Is provided.

1 is an FT-IR spectrum of nanofibers comprising electrospin fibers according to an embodiment.
2 is a WAXD pattern of nanofibers comprising electrospin fibers according to an embodiment.
3 is a TGA curve of nanofibers comprising electrospin fibers according to an embodiment.
4 is a graph showing a diameter distribution of nanofibers including the electrospin fibers according to the embodiment.
FIG. 5 is a SEM photograph and a water contact image of a nanofiber including an electrospin fiber according to an embodiment. FIG.
6 is a graph showing the cell adhesion rate after inoculating MC3T3-E1 on the skeleton of the nanofibers containing the electrospin fibers according to the embodiment.
7 is a SEM photograph after inoculation of MC3T3-E1 on the skeleton of the nanofibers containing the electrospin fibers according to the embodiment.

EMBODIMENT OF THE INVENTION Hereinafter, the nanofiber of this invention, its manufacturing method, and a cell scaffold material are demonstrated based on embodiment.

The nanofibers according to the embodiment have a copolymer of polycaprolactone (PCL), polyethylene glycol (PEG) and polyhedral oligosilsesquioxane (POSS). Here, a nanofiber means the fiber of the less than 1 micrometer in diameter mostly. Nanofibers according to the embodiment are excellent in mechanical strength and shape stability, and are also excellent in biodegradability and biocompatibility. In addition, the nanofiber may contain other components as long as it does not contradict the purpose.

In this embodiment, POSS is a polyhedral oligo silsquioxane represented by following formula (3).

(However, in the formula (3), R represents a cyclohexyl group)

In this embodiment, the number average molecular weight of PEG is 3400-8000. PEG forms a straight chain structure and may be represented by the following Chemical Formula 4.

In the present embodiment, the copolymer of PEG and POSS may be represented by the following formula (5).

(In Formula 5, R represents a cyclohexyl group.)

The nanofibers according to the embodiment are produced by the electrospinning method. More specific manufacturing methods include a mixing step of mixing a solution containing PCL, a solution containing a copolymer of PEG and POSS, and a fiberizing step of obtaining nanofibers from the mixed solution obtained in the mixing step by the electrospinning method. Moreover, if the nanofiber which has the same component as the nanofiber which concerns on embodiment is obtained, you may manufacture a nanofiber by methods other than the electrospinning method.

In the present embodiment, the copolymer of PEG and POSS is obtained by urethane-bonding PEG with isocyanatopropyldimethylsilylcyclohexyl-polyhedral oligosilsesquioxane, which is a macromonomer of POSS. This urethane bond is produced between dibutyltin dilaurate (DBTDL) as a catalyst and between the terminal diol of PEG and the monoisocyanate group of the macromonomer of POSS.

[Example]

[Raw material]

PCL obtained the number average molecular weight of 80 kDa (Hereinafter, only "80k". The same also for other polymers) from Sigma Aldrich Japan.

PEG had 3.4 k and 8.0 k of number average molecular weights, and was refine | purified and used the thing made by Aldrich. This purification was carried out by repeating the process of precipitating PEG by adding a chloroform solution of PEG to n-hexane.

The propyldimethylsilylcyclohexyl isocyanate-polyhedral oligosilsquioxane (Isocyanatopropyldimethylsilylcyclohexyl-polyhedral oligosilsesquioxane) which is a macromonomer of POSS was obtained from Tomen Plastic Co., Ltd. DBTDL, a catalyst for direct urethane bonds, was used as it was, having a purity of 95% by Aldrich.

Amphiphilic, telechelic copolymer of PEG3.4k and POSS (hereinafter referred to as "PEG3.4 k-POSS". The same applies to other copolymers. In some cases, the number average molecular weight of PEG may not be described.) And PEG 8.4 k-POSS were synthesized by direct urethane bonding between the terminal diol of PEG and the monoisocyanate group of the macromonomer of POSS using DBTDL as a catalyst.

Amphiphilic, telechelic type PEG3.4k-POSS and amphiphilic, telechelic type PEG8.0k-POSS were synthesized by urethane reaction and confirmed by ¹ H-NMR measurement. That is, as the H signal of the 3.15 ppm -CH ₂ -NCO group disappeared, a 4.26 ppm chemical shift indicating that a urethane bond was formed was found.

In addition, the POSS content in the amphiphilic and telechelic type PEG3.4k-POSS and the POSS content in the amphiphilic and telechelic type PEG8.0k-POSS were measured by cyclohexyl resonance of POSS macromonomer at ¹ H-NMR. It can calculate quantitatively by observing as

When the number of functional groups at the terminal of the PEG-POSS was calculated, the terminal of the amphiphilic and the telechelic type PEG3.4k-POSS was 2.1, and the terminal of the amphiphilic and the telechelic type PEG8.0k-POSS was 1.9. In addition, the calculated content of the POSS macromonomer in PEG3.4k-POSS and the calculated content of the POSS macromonomer in PEG8.0k-POSS were almost the same as the supply amount of the macromonomer of POSS.

Electrospinning

First, the liquid mixture of PCL and PEG3.4k-POSS, the liquid mixture of PCL and PEG8.0k-POSS, and the liquid mixture of PCL and PEG8.0k were produced. These mixed solutions were prepared by dissolving PCL in a mixed solvent of chloroform: DMF = 9: 1 (weight ratio) to 12wt%, PEG3.4k-POSS of telechelic type, PEG8.0k-POSS of telechelic type, and PEG8. 0k was dissolved in DMF overnight at room temperature to obtain a mixture.

In addition, each weight of the telechelic type PEG3.4k-POSS, the telechelic type PEG8.0k-POSS, and PEG8.0k in these mixed liquids was about 30 wt% based on the weight of PCL.

Subsequently, these mixed liquids were supplied to the capillary tip using a plastic syringe. And the copper wire connected to the positive electrode (anode) of the electrospinning apparatus was inserted in the liquid mixture, and also the negative electrode (cathode) was attached to the metal collector. The distance between the capillary tip and the collector was fixed at 15 cm, and the voltage between the anode and cathode was fixed at 12 kV.

And a direct current voltage was applied to the liquid mixture of PCL and PEG3.4k-POSS, the liquid mixture of PCL and PEG8.0k-POSS, and the liquid mixture of PCL and PEG8.0k, and electrospinning to manufacture the nanofiber. Each of these liquid mixtures was electrospinned by a metal collector rotating at room temperature. In this way, each nanofiber was obtained. Hereinafter, the nanofiber obtained by the electrospinning method is only described as "electrospin fiber."

In addition, the electrospin fiber obtained from the liquid mixture of PCL and PEG3.4k-POSS is described as "PCL / PEG3.4k-POSS", and the electrospin fiber obtained from the liquid mixture of PCL and PEG8.0k-POSS is called "PCL / PEG8. 0 k-POSS ", and the electrospin fiber obtained from the liquid mixture of PCL and PEG8.0k is described as" PCL / PEG8.0k. "

[Translate]

(1) FT-IR

The FT-IR analysis of the electrospin fiber was performed in the range of 600-4000 cm <^-1> using IRPrestige-21 (made by Shimadzu Corporation).

1 is the FT-IR spectrum of each electrospin fiber and POSS of PCL (neatPCL), PCL / PEG8.0k-POSS, PCL / PEG3.4k-POSS and PCL / PEG8.0k.

Spectrum of the electro spin the fibers of the PCL, and the characteristic peaks in the C = O stretching and CC, CO stretching 1720cm ^-1 and 1162cm ^-1 due to these peaks it shows a semi-crystalline PCL. These peaks are attributable to a small shoulder band of 1734cm ^-1 1722cm ^-1 of the crystalline PCL of relatively sharp carbonyl band of the amorphous PCL.

On the other hand, the crystalline C = O stretching of PCL in PCL / PEG 3.4k-POSS and PCL / PEG8.0k-POSS was relatively decreased. This indicates that there is an interaction between PCL and PEG-POSS. A clear band of 890 cm ^-1 was also identified, indicating the presence of POSS in PCL / PEG 3.4k-POSS and in PCL / PEG8.0k-POSS. This band is due to the bending mode of the Si-OH group.

(2) wide-angle X-ray diffraction (WAXD)

Wide angle X-ray diffraction (WAXD) of the electrospin fibers was performed using an X-ray diffractometer (Rotaflex RTP300, manufactured by Rigak Co., Ltd.) at a scanning speed of 2 ° per minute at 40 kV and 150 mA at room temperature. It carried out in the range of ° -40 degree. In addition, the irradiation source of CuK (alpha) ray was set to wavelength 1.5402 Hz. The crystallinity of the obtained PCL / PEG-POSS is very important when PCL / PEG-POSS is used as a biodegradable cell scaffolding material. This is because crystallinity has a decisive influence on structure, physical properties (eg, mechanical properties, etc.) and biodegradability.

2 is a WAXD pattern of each electrospin fiber of PCL (neatPCL), PCL / PEG3.4k-POSS, PCL / PEG8.0k-POSS, and PCL / PEG8.0k. WAXD patterns were measured to investigate the effect of PEG-POSS on the microstructure of PCL.

As shown in FIG. 2, each electrospin fiber of PCL / PEG-POSS exhibited three characteristic peaks of 2θ = 21.4 ° (strong), 21.9 ° (shoulder), and 23.6 ° (middle). These correspond to the reflections of [110], [111], and [200], and are the same as the fine crystal structure of the electrospin fibers of PCL.

Peak intensities of PCL / PEG 3.4k-POSS, PCL / PEG8.0k-POSS, and PCL / PEG8.0k are slightly decreasing compared to the electrospin fibers of PCL. This is due to the bulky POSS inhibiting the crystallization of PCL. In addition, strong reflection of 2θ = 7.5 ° by crystal POSS was clearly observed. Further, a diffraction phenomenon of PEG in PCL / PEG8.0k produced a peak at 2θ = 18.8 ° corresponding to the reflection of [120].

As mentioned above, it turned out that each electrospin fiber of PCL / PEG3.4k-POSS and PCL / PEG8.0k-POSS has the same mechanical strength, shape stability, and biodegradability as the electrospin fiber of PCL (neatPCL). That is, it was found that each of the electrospin fibers of PCL / PEG 3.4k-POSS and PCL / PEG8.0k-POSS had excellent mechanical strength and shape stability and excellent biodegradability, similar to those of the PCL electrofin fibers.

(3) TG / DTA

Thermogravimetric analysis (TGA) was performed to investigate the thermal stability and miscibility of each electrospin fiber of PCL, PCL / PEG3.4k-POSS, PCL / PEG8.0k-POSS, and PCL / PEG8.0k. Carried out. Thermogravimetric analysis used TG / DTA6200 (made by Seiko Instruments Inc.) on the conditions of 20 degreeC of temperature increase rate every minute in nitrogen atmosphere.

3 is a TGA curve of each electrospin fiber of PCL (neatPCL), PCL / PEG3.4k-POSS, PCL / PEG8.0k-POSS, and PCL / PEG8.0 k. As shown in FIG. 3, the thermal stability of PCL / PEG8.0k (Td: 240 ° C.) is significantly reduced when it exceeds 240 ° C. as compared to the electrospin fibers (Td: 320 ° C.) of PCL. On the other hand, the electrospin fiber of PCL which injected the telechelic type PEG-POSS showed favorable thermal stability because it injected the macromonomer of POSS.

However, the electrospin fibers of PCL / PEG 3.4 k-POSS exhibited the first degradation with a 20% weight loss near 200 ° C. This is similar to the degradation behavior of electrospin fibers of PCL / PEG. In addition, the thermal stability of the electrospin fibers of PCL / PEG 3.4k-POSS exceeded the thermal stability of the electrospin fibers of PCL when it exceeded 350 ° C. Since the electrospin fibers of PCL / PEG-POSS were injected with POSS, the PCL residue (the amount of carbides and ceramics produced) increased compared with the electrospin fibers of PCL.

(4) Electron microscope observation, water contact angle

The structure and diameter of the electrospin fibers were determined by scanning electron microscopy (SEM). The scanning electron microscope apparatus measured by applying the electric potential of 20 kV to each electrospin fiber sample which sputtered Pd-Pt using S-3000N of Hitachi Seisakusho. In addition, the diameter of the electrospin fiber was measured using image processing software ImageJ. The average value of the diameter of the electrospin fiber was made into the average value measured 150 times.

4 is a graph showing the diameter distribution of each electrospin fiber of (a) PCL, (b) PCL / PEG3.4k-POSS, (c) PCL / PEG8.0k-POSS, and (d) PCL / PEG8.0k. to be. As shown in FIG. 4, the average diameter of each electrospin fiber was 713 ± 408 nm for PCL, 528 ± 253 nm for PCL / PEG 3.4k-POSS, 479 ± 326 nm for PCL / PEG8.0k-POSS, and PCL / PEG8. .0k was 607 ± 343 nm. Electrospin fibers of the telechelic type PEG-POSS (PCL / PEG3.4k-POSS and PCL / PEG8.0 k-POSS) are compared to the electrospin fibers of PCL and the electrospin fibers of PCL / PEG8.0k. The diameter was small and the fiber diameter distribution was narrow.

The water contact angle of each electrospin fiber was measured using the contact angle analyzer (Kyogawa Kaimen Chemical Co., Ltd. DM-CE1). Specifically, about 1.3 μL of water droplets are dropped from the microcylinder onto the surface of each electrospin fiber, and the appearance of the dropped water droplets is captured by a high resolution camera, and the contact shape analyzer DSA100 (manufactured by Kruss, Germany) and the multifunctional integrated analysis software The angle was calculated using FAMAS. The average value of 15 measurements was made into water contact angle data. In addition, each electrospin fiber used the thing dried under reduced pressure at 50 degreeC for 4 days.

FIG. 5 shows SEM photographs and respective electrophores of each electrospin fiber of (a) PCL, (b) PCL / PEG3.4k-POSS, (c) PCL / PEG8.0k-POSS, and (d) PCL / PEG8.0k. It is a water contact image of spin fiber. Electrospin fibers are deposited in a state in which the fiber direction is random.

The water contact angle of the PCL electrospin fibers is about 129.8 ± 1.4 °, indicating that the electrospin fibers of the PCL are hydrophobic. However, the water contact angle of PCL / PEG3.4k-POSS is 96.7 ± 5.4 °, the water contact angle of PCL / PEG8.0k is 74.9 ± 7.5 °, and the water contact angle of PCL / PEG8.0 k-POSS is 36.5 ± 1.5 °. It was. This shows that hydrophilicity-hydrophobicity can be adjusted by injecting hydrophilic PEG and / or hydrophobic POSS into the electrospin fibers of PCL.

[Cell Culture]

First, each of the electrospin fibers of PCL / PEG 3.4k-POSS, PCL / PEG8.0k-POSS, and PCL / PEG8.0k was sterilized by soaking in 99% ethanol for 30 minutes. This sterilization step was performed twice. Subsequently, each electrospin fiber was washed three times with distilled water to remove residual ethanol. Subsequently, the osteoblast-like cells MC3-T3E1 obtained from the Bank of Science and Technology on each electrospin fiber were passaged for 13 generations.

Specifically, MC3T3-E1 was inoculated into the cell scaffold material of each electrospin fiber, and the cells cultured for 3 hours, 6 hours, and 24 hours were soaked in a 10% formaldehyde solution overnight under conditions of a temperature of 4 ° C. Subsequently, the process of sequentially processing each electrospin fiber cultured with ethanol in which the concentration was gradually increased to 50%, 60%, 70%, 80%, 90%, and 99% (twice) (step 1, 5 minutes) was performed. Dehydrated five times. Finally, each sample was electrolyzed overnight using t-butyl alcohol (manufactured by Wako Chemical Co., Ltd.) to obtain a sample for analysis.

The culture was carried out using a medium of αMEM (trade name GIBCO) at a temperature of 37 ° C. under a CO ₂ 5% atmosphere and a cell concentration of 5 × 10 ⁴ cells / well. The medium contains 10% heat inactivated fetal bovine serum (FBS), 100 U / mL streptomycin, and 0.1% β-glypyrroline acid ester. This medium was used to induce osteoblast differentiation.

In addition, the culture was carried out in tissue culture dishes (TCDs). As a tissue culture dish, a polystyrene dish (brand name Nunc) manufactured by Thermo Fisher Scientific (Denmark) was used. To ensure a sufficient supply of nutrients to the culture dish, the medium was changed once every two days.

[Cell adhesion]

FIG. 6 shows cells inoculated with MC3T3-E1 on the skeleton of each of the electrospin fibers of PCL / PEG3.4k-POSS, PCL / PEG8.0k-POSS, and PCL / PEG8.0k. It is a graph showing the cell adhesion rate after incubation. The cell adhesion rate was calculated by the following formula by counting the number of cells present in the medium after cell culture. In addition, the cell number employ | adopted the average value of 3 times.

Cell adhesion rate (%) = {1- suspended cell number / (5.0 × 10 ⁴ )} × 100

As shown in FIG. 6, PCL / PEG 3.4k-POSS and PCL / PEG8.0k-POSS had a high adhesion rate at the beginning of cell culture compared to PCL / PEG8.0k. This is considered to be because the surface energy of the siloxane site | part in POSS is high. It can be seen that the cell scaffold material of PCL / PEG-POSS according to the embodiment is not toxic after 24 hours of cell culture and maintains a good cell adhesion rate (~ about 93%) between the cell scaffold material surface and the cells. there was. Accordingly, it was found that the electrospin fibers of PCL / PEG 3.4k-POSS and PCL / PEG8.0k-POSS were excellent in biocompatibility and adhesion to cells.

Figure 7 Cell incubation for 3 and 6 hours by inoculation of MC3T3-E1 on the skeleton of each electrospin fiber of PCL, PCL / PEG3.4k-POSS, PCL / PEG8.0 k-POSS, and PCL / PEG8.0k. It is SEM photograph after one. The degree of adhesion, proliferation, and interaction of the cells of each of these electrospin fibers was examined by SEM photograph.

In this example, the cell scaffold material of each electrospin fiber had little cytotoxicity to MC3T3-E1 cells. As shown in FIG. 7, MC3T3-E1 cells adhered correctly to the cell scaffolding material of each electrospin fiber of the examples, and formed aggregates smoothly according to the cell culture time. In addition, MC3T3-E1 cells cultured with PCL electrospin fibers had relatively little cell adhesion after 6 hours of cell culture.

On the other hand, each of the electrospin fibers of PCL / PEG 3.4k-POSS and PCL / PEG8.0k-POSS had very high cell adhesion after cell culture for 3 hours, compared to the electrospin fibers of PCL. In addition, after 6 hours of cell culture, it was confirmed that most of the MC3T3-E1 cells began to expand the cytoplasm. In other words, it was found that the nanofibers according to the embodiment had high adhesion to cells, that is, excellent adhesion to cells.

From the above, PCL's electrospin fibers incorporating amphiphilic PEG-POSS have high expectations as future biomedical materials, particularly cell scaffolding materials.

In addition, poly (ester-urethane) (PEU), porous composite film of POSS (POSS-PEU), and poly (carbonate silsesquioxane-urea) (POSS-PCSBU) are known as cell scaffolding materials using POSS. See, for example, YLGuo et al., "J. Tissue.Eng.Reg.Med." 2010, Vol. 4, No. 7, p.553-564).

The nanofiber or cell scaffolding material (POSS-PEG / PCL) of this invention is a POSS compound (POSS-PEG) which becomes a raw material compared with the case of the above-mentioned conventional POSS containing material (POSS-PEU or POSS-PCSBU). Is easy to synthesize.

In addition, since the nanofiber or cell scaffold material (POSS-PEG / PCL) of the present invention uses PEG having a high affinity for cells as a raw material, the above-described conventional POSS-containing material (POSS-PEU or POSS-PCSBU) In comparison with the case, adhesion to cells is excellent.

In addition, since the nanofiber or cell scaffold material (POSS-PEG / PCL) of the present invention uses PCL having excellent biodegradability as a raw material, it is compared with the conventional POSS-containing material (POSS-PEU or POSS-PCSBU) described above. Excellent biodegradability

In addition, the method for producing a nanofiber of the present invention can produce a cell scaffold material superior to the above-described conventional POSS-containing materials (POSS-PEU or POSS-PCSBU) by a simple process of mixing PCL.

Claims (9)

Polycaprolactone,
A nanofiber comprising a copolymer of polyethylene glycol and polyhedral oligosilsesquioxane. The method of claim 1,
The polyhedral oligosilsquioxane is a polyhedral oligosilsquioxane represented by the following formula (1).
(Formula 1)

(However, in formula (1), R represents an alkyl group, R 'represents a functional group having a reactive group at the terminal) 3. The method according to claim 1 or 2,
The number average molecular weight of the said polyethylene glycol is 3400-8000, The nanofiber characterized by the above-mentioned. The method according to any one of claims 1 to 3,
The nanofiber is nanofibers, characterized in that produced by the field emission method. A mixing step of mixing a solution containing polycaprolactone and a solution containing a copolymer of polyethylene glycol and polyhedral oligosilsesquioxane, and
It has a fiberization process which obtains a nanofiber from the mixed solution obtained at the said mixing process by the electrospinning method, The manufacturing method of the nanofiber characterized by the above-mentioned. The method of claim 5, wherein
The polyhedral oligosilsquioxane is a polyhedral oligosilsquioxane represented by the following formula (2).
(2)

(However, in formula (2), R represents an alkyl group, R 'represents a functional group having a reactive group at the terminal) The method according to claim 5 or 6,
Preparation of nanofibers further comprising a copolymer synthesis step of obtaining a copolymer by urethane-bonding polyethylene glycol and propyldimethylsilylcyclohexyl isocyanate-polyhedral oligosilsquioxane (Isocyanatopropyldimethylsilylcyclohexyl-polyhedral oligosilsesquioxane) before the mixing step Way. 8. The method according to any one of claims 5 to 7,
The number average molecular weight of the polyethylene glycol is 3400 ~ 8000 method for producing nanofibers. A cell scaffolding material comprising the nanofiber according to any one of claims 1 to 4.

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