• 한국생물공학회:학술대회논문집
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• 2000.04a
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• pp.141-144
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• 2000

Highly open porous polymer matrices are required for high density cell seeding, efficient nutrient, and oxygen supply to the cells cultured in the three dimensional matrices. However, there are severe problems of mass transfer limitations within the cell/scaffolds culture system. Thus we hypothesize that continuos-flow culture conditioning of cells with the scaffolds may improve the cell viability and the differentiated function. In this study, we fabricated porous PLGA scaffolds by using gas-foaming/salt-leaching method as previous described. Viscous PLGA gel paste contains ammonium bicarbonate particulates, acting as a gas-foaming agent as well as a salt-leaching porogen, were cast into Teflon mold and dried. Ammonium bicarbonate salt upon contact to an acidic aqueous solution evloves gaseous ammonia and carbon dioxide by itself. And we conjugated galactose moiety [AGA; $N-(aminobuty1)-O-{\beta}-D-galactopyranosyl-(1{\rightarrow}4)-D-glucoamide]$ to the terminal end group of a PLGA to increase the cell adhesion and matain the differentiated function of hepatocytes. Cell-seeded scaffolds were secured in a flow bioreactor chamber and exposed to continuous flow at 5 ml/min. As a result of our study, the high yield of hepatocytes attachment was accomplished by increasing the concentration of PLGA-AGA conjugate in polymer scaffolds and cells in the scaffolds under continuos flow condition maintained a high level of viability and albumin secretion rate of cultured hepatocytes showed a higher level that of control groups.

• Polymer(Korea)
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• v.33 no.5
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• pp.469-476
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• 2009

In this study, biodegradable superporous hydrogels(SPHs) with fast swelling and superabsorbent properties were prepared using biodegradable crosslinkers and their physicochemical properties were characterized. A biodegradable crosslinker (PLA-PEG-PLA DA) was synthesized by a ring opening polymerization of D,L-lactide (LA) using hydrophilic poly(ethylene glycol) as a macroinitiator, followed by diacrylation of the end groups for the introduction of polymerizable vinyl groups. Various kinds of hydrogels with different chemical compositions were prepared and characterized in terms of swelling ratio, swelling kinetics, and biodegradation properties. The synthetic results were confirmed by $^1H$-NMR, FT-IR and GPC measurements, and the porous structures of the prepared SPHs and their porosities were identified by a scanning electron microscope and mercury porosimetry, respectively. The physicochemical properties of SPHs could be controlled by varying their chemical compositions and their cytotoxicity were found to be very low by MTT assay.

• Bulletin of the Korean Chemical Society
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• v.35 no.8
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• pp.2342-2348
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• 2014

Poly(lactic-co-glycolic acid) (PLGA) were grafted to both ends of Pluronic$^{(R)}$ F68 ($(EO)_{75}(PO)_{30}(EO)_{75}$) triblock copolymer to produce poly{(lactic acid)$_m$-co-(glycolic acid)$_n$}-b-poly(ethylene oxide)$_{75}$-b-poly(propylene oxide)$_{30}$-b-poly(ethylene oxide)$_{75}$-b-poly{(lactic acid)$_m$-co-(glycolic acid)$_n$} (PLGA-F68-PLGA) pentablock copolymers. Molecular weights of PLGA blocks were controlled and five kinds of pentablock copolymers with different PLGA block lengths were synthesized using in-situ ring-opening polymerization of D,L-lactide and glycolide with tin(II) 2-ethylhexanoate ($Sn(Oct)_2$) catalyst. PLGA-F68-PLGA pentablock copolymers were characterized by $^1H$- and $^{13}C$-NMR, GPC, and TGA. The numbers (2m, 2n) of repeating units for lactic acid and glycolic acid inside PLGA segments were obtained as (48, 17), (90, 23), (125, 40), (180, 59), and (246, 64), with $^1H$-NMR measurement. From NMR data, the resultant molecular weights were determined in the range of 12,700-29,700, which were similar to those obtained from GPC. Polydispersity index was increased in the range of 1.32-1.91 as the content of PLGA blocks increased. TG and DTG thermograms showed discrete degradation traces for PLGA and F68 blocks, which indicate the weight fractions of PLGA blocks in pentablock copolymers can be calculated by TG profile and it is possible to remove PLGA block selectively. Hydrodynamic radius and radius of gyration of pentablock copolymer micelle were obtained in the range of 46-68 nm and 31-49 nm, respectively, in very dilute (i.e. 0.005 wt %) aqueous solution of THF:$H_2O$ = 10:90 by volume at $25^{\circ}C$.

• Polymer(Korea)
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• v.27 no.3
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• pp.226-234
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• 2003

Ipriflavone (IP), a non-hormonal isoflavone derivative, has been shown to interfere with bone remodeling by inhibiting bone resorption and stimulating bone formation. IP consistently increased the amount of Ca incorporated into the cell layer by mesenchymal stem cells (MSCs). In this study, we developed the novel IP loaded poly(L-lactide-co-glycolide) (PLGA) scaffolds for the possibility of the application of the tissue engineered bone. IP/PLGA scaffo1ds were prepared by solvent casting/salt leaching method and were characterized by porosimeter, scanning electron microscopy, determination of residual salt amount, differential scanning calorimetry, and X-ray diffractometer, respectively. IP/PLGA scaffolds were implanted into the back of athymic nude mouse to observe the effect of IP on the osteoinduction compared with control PLGA scaffo1ds. Thin sections were cut from paraffin embedded tissues and histological sections were stained H&E, von Kossa, and immunohistochemical staining for Type I collagen and osteocalcin. It can be observed that the porosity was above 91.7% and the pore size was above 101 $\mu\textrm{m}$. Control scaffo1d and IP/PLGA scaffo1ds of 50% IP were implanted on the back of athymic nude mouse to observe the effect of IP on the induction of cells proliferation for 9 weeks. The evidence of calcification, osteoblast, and osteoid from the undifferentiated stem cells in the subcutaneous sites and other soft connective tissue sites having a preponderance of stem cells has been observed. From these results, it seems that IP plays an important role for bone induction in IP/PLCA scaffolds.

• Proceedings of the Polymer Society of Korea Conference
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• 2006.10a
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• pp.263-263
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• 2006

Poly (ethylene glycol)(PEG) - Poly (${\varepsilon}-caprolactone(CL)$) - Poly (D,L lactide(LA) (PCLA-PEG-PCLA) was synthesized by ring-opening polymerization to form temperature sensitive hydrogel triblock copolymer. The triblock copolymer was acrylated by acryloyl chloride. ${\beta}-amino$ ester was used as a pH sensitive moiety, in this study ${\beta}$- amino ester obtained from 1,4-butandiol diacrylate, and 4, 4' trimethylene dipiperidine, it have pKb around 6.6. pH/temperature sensitive penta-block copolymer (PAE-PCL-PEG-PCL-PAE) was synthesized by addition polymerization from acrylated triblock copolymer, 1,4-butandiol diacrylate, and 4, 4' trimethylene dipiperidine. Their physicochemical properties of triblock and penta-block copolymers were characterized by $^1H-NMR$ spectroscopy and gel permeation spectroscopy. Sol-gel phase transition behavior of PAE-PCL-PEG-PCL-PAE block copolymers were investigated by remains stable method. Aqueous media of the penta-block copolymer (at 20 wt%) changed from a sol phase at pH 6.4 and $10^{\circ}C$ to a gel phase at pH 7.4 and $37^{\circ}C$. The sol-gel transition properties of these block copolymers are influenced by the hydrophobic/hydrophilic balance of the copolymers, block length, hydrophobicity, stereo-regularity of the hydrophobic of the block copolymer, and the ionization of the pH function groups in the copolymer depended on the changing of environmental pH, respectively. The degradation and the stabilization at pH 7.4 and $37^{\circ}C$, and the stabilization at pH 6.4 and $10^{\circ}C,\;5^{\circ}C,\;0^{\circ}C$, of the gel were determined. The results of toxicity experiment show that the penta block copolymer can be used for injection drug delivery system. The sol?gel transition of this block copolymer also study by in vitro test ($200{\mu}l$ aqueous solution at 20wt% polymer was injected to mouse). Insulin loading and releasing by in vitro test was investigated, the results showed that insulin can loading easily into polymer matrix and release time is around 14-16days. The PAE-PCL-PEG-PCL-PAE can be used as biomaterial for drug, protein, gene loading and delivery.

• Macromolecular Research
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• v.13 no.6
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• pp.467-476
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• 2005

The main objective of this study was to develop and characterize pH-sensitive biodegradable polymeric materials. For pH-sensitivity, we employed three kinds of moieties: 2-amino-3-(lH-imidazol-4-yl)-propionic acid (H), N-[4-( 4,6-dimethyl-pyrimidin-2ylsulfamoyl)-phenyl]succinamic acid (SM), and 2- {3-[ 4-( 4,6-dimethyl-pyrim­idin- 2-ylsulfamoyl)-phenylcarbamoyl]-propionylamino} -3-(3 H - imidazol-4-yl)-propionic acid (SH). The pH -sensitive diblock copolymers were synthesized by ring opening polymerization and coupling reaction from poly(ethylene glycol) (MPEG), $\varepsilon$-caprolactone (CL), D,L-lactide (LA) and pH-sensitive moieties. The pH-sensitive SH molecule was synthesized in a two-step reaction. The first step involved the synthesis of SHM, a methyl ester derivative of SH, by coupling reaction of SM and L-histidine methyl ester dihydrochloride, whereas the second step involved the hydrolysis of the same. The synthesized SM, SHM and SH molecules were characterized by FTIR, $^{1}H$-NMR and $^{13}C$-NMR spectroscopy, whereas diblock copolymers and pH-sensitive diblock copolymer were characterized by $^{1}H$-NMR and GPC analysis. The critical micelle concentrations were determined at various pH conditions by fluorescence technique using pyrene as a probe. The micellization and demicellization studies of pH-sensitive diblock copolymers were also done at different pH conditions. The pH-sensitivity was further established by acid-based titration and DLS analysis.

• Macromolecular Research
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• v.11 no.5
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• pp.352-356
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• 2003

The objectives of this study were to investigate the influence of gamma irradiation for sterilization on poly(D,L-lactide-co-glycolide) (PLGA) with different molecular weight and the effect of gamma irradiation on the release behavior of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine) from PLGA wafer with various irradiation doses. The effect of gamma irradiation on PLGA was evaluated by gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and electron paramagnetic resonance (EPR). The weight average molecular weight (M$_{w}$) and glass transition temperature (T$_{g}$) of PLGA decreased after gamma irradiation. The extent of M$_{w}$ reduction was dependent on irradiation dose and PLGA molecular weight. Using EPR spectroscopy, we successfully detected gamma irradiation induced free radicals in PLGA. The gamma irradiation increased the release rate of BCNU from PLGA wafer at applied irradiation doses except 2.5 Mrad of irradiation dose in this study.study.

• Journal of Pharmaceutical Investigation
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• v.34 no.5
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• pp.369-377
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• 2004

The objective of this study was to investigate the patterns of protein leaching to an external phase during an ethyl acetate-based, double emulsion microencapsulation process. An aqueous protein solution (lactoglobulin, lysozyme, or ribonuclease; $W_1$) was emulsified in ethyl acetate containing poly-d,l-lactide-co-glycolide 75:25. The $W_1/O$ emulsion was transferred to a 0.5% polyvinyl alcohol solution saturated with ethyl acetate $(W_2)$. After the double emulsion was stirred for 5, 15, 30, or 45 min, additional 0.5% polyvinyl alcohol $(W_3)$ was quickly added into the emulsion. This so-called quenching step helped convert emulsion microdroplets into microspheres. After 2-hr stirring, microspheres were collected and dried. The degree of protein leaching to $W_2$ and/or $W_3$ phase was monitored during the microencapsulation process. In a separate, comparative experiment, the profile of protein leaching to an external phase was investigated during the conventional methylene chloride-based microencapsulation process. When ethyl acetate was used as a dispersed solvent, proteins continued diffusing to the $W_2$ phase, as stirring went on. Therefore, the timing of ethyl acetate quenching played an important role in determining the degree of protein microencapsulation efficiency. For example, when quenching was peformed after 5-min stirring of the primary $W_1/O$ emulsion, the encapsulation efficiencies of lactoglobulin and ribonuclease were $55.1{\pm}4.2\;and\;45.3{\pm}7.6%$, respectively. In contrast, when quenching was carried out in 45 min, their respective encapsulation efficiencies were $39.6{\pm}3.2\;and\;29.9{\pm}11.2%$. By sharp contrast, different results were attained with the methylene-chloride based process: up to 2 hr-stirring of the primary and double emulsions, less than 5% of a protein appeared in $W_2$. Afterwards, it started to partition from $W_1\;to\;W_2/W_3$, and such a tendency was affected by the amount of PLGA75:25 used to make microspheres. Different solvent properties (e.g., water miscibility) and their effect on microsphere hardening were to be held answerable for such marked differences observed with the two microencapsulation processes.

• Journal of Biomedical Engineering Research
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• v.27 no.5
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• pp.218-223
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• 2006

We examined the effects of ${\beta}$-glucan-reinforced PLGA film and scaffold on HDFs (human dermal fibroblast) attachment and proliferation. The PLGA films were prepared by simple solvent-casting method. The prepared films were grafted with $(1{\to}3)(1{\to}6)-{\beta}-glucan$ in various ratios after plasma treatment on surface. The surface of the film was characterized by contact angle measurement, scanning electron microscope (SEM), and Fourier-transform infrared spectrophotometer (FT-IR). The amount of $(1{\to}3)(1{\to}6)-{\beta}-glucan$ in the prepared film was indirectly determined by phenol-sulfuric acid method. The HDFs (Human dermal fibroblasts) were used to evaluate the cell attachment and proliferation on PLGA specimens before and after plasma/${\beta}-glucan$ treatment. The result showed that the plasma treated groups exhibited more mont of ${\beta}-glucan$ might be grafted than the non plasma treated groups. Cell attachment was significantly enhanced in the plasma/${\beta}-glucan$ grafted group after 4 hours incubation (p<0.05) due to the improved hydrophilicity and cytoactivity effect of the ${\beta}-glucan$. The cell proliferation of plasma/${\beta}-glucan$ (2mg/ml) grafted group was the highest rate among the groups (p<0.05).

• Journal of the Korean Magnetics Society
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• v.16 no.1
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• pp.107-110
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• 2006

Magnetite nanoparticles encapsulated with biodegradable polymer [poly(D,L-lactide-co-glycoiide), PLGA] were prepared by an emulsification-diffusion method. To investigate the effect of type of organic solvents on the mean particle sizes of obtained composite particles, different organic solvents [ethyl acetate (EA), propylene carbonate (PC) and acetone (ACE)] were used with a stabilizer [didodecyl dimethyl ammonium bromide (DMAB)]. The particle size of nanoparticles was observed by the dynamic light scattering method. When EA and PC as partially water-soluble solvents were used, small composite nanoparticles below 80nm were obtained, while large composite nanoparticles above 330nm were prepared for ACE as a fully water-soluble solvent.