Neurogenesis of bone marrow-derived mesenchymal stem cells onto β-mercaptoethanol-loaded PLGA film.

Khang, Gilson,Kim, Hye Lin,Hong, Minsung,Lee, Dongwon Springer 2012 Cell and tissue research Vol.347 No.3

<P>Bone marrow-derived mesenchymal stem cells (BMSCs) are of particular interest in the field of tissue engineering because of their potential to differentiate into osteoblasts, chondrocytes, and neuronal cells. In order to promote the differentiation of BMSCs into specific cell types, appropriate scaffold biomaterials and bioactive molecules that can support the differentiation of BMSCs into specific cell types are needed. We hypothesized that β-mercaptoethanol (BME), which has been reported to induce the differentiation of BMSCs into neural-like cells, promotes BMSCs to differentiate into neural-like cells when BME is added to polymeric scaffolds containing the BMSCs. We fabricated biocompatible film shaped scaffolds composed of poly(lacti-co-glycolic) acid (PLGA) and various concentrations of BME to confirm that BME-promoted differentiation of BMSCs is concentration-dependent. Cell proliferation increased as the BME concentration in the films increased at the early stage, and the proliferation rate remained similar on the PLGA films for 3?weeks following the BMSC seeding. The expression of neuronal markers in differentiated BMSCs was assessed by RT-PCR. At 2- and 3-week time-points, mRNA expression of neurofilament and neuron specific enolase was significantly increased in PLGA/BME films containing 400?μM BME compared to PLGA films. Thus, we have identified BMSC-seeded PLGA/BME films with 200?μM and 400?μM BME as potentially useful candidates for neural tissue engineering applications by promoting BMSC proliferation and differentiation towards neural-like cells.</P>

Preparation and Characterization of Small Intestine Submucosa Powder Impregnated Poly(L-lactide) Scaffolds: The Application for Tissue Engineered Bone and Cartilage

Khang, Gilson,Rhee, John M.,Shin, Philkyung,Kim, In Young,Lee, Bong,Lee, Sang Jin,Lee, Young Moo,Lee, Hai Bang,Lee, Ilwoo The Polymer Society of Korea 2002 Macromolecular Research Vol.10 No.3

In order to endow with new bioactive functionality from small intestine submucosa (SIS) powder as natural source to poly (L-lactide) (PLA) and poly (lactide-co-glycolide) (PLGA) synthetic biodegradable polymer, porous SIS/PLA and SIS/PLGA as natural/synthetic composite scaffolds were prepared by means of the solvent casting/salt leaching methods for the possibility of the application of tissue engineered bone and cartilage. A uniform distribution of good interconnected pores from the surface to core region was observed the pore size of 40~500 ${\mu}{\textrm}{m}$ independent with SIS amount using the solvent casting/salt leaching method. Porosities, specific pore areas as well as pore size distribution also were almost same. After the fabrication of SIS/PLA hybrid scaffolds, the wetting properties was greatly enhanced resulting in more uniform cell seeding and distribution. Five groups as PGA non-woven mesh without glutaraldehyde (GA) treatment, PLA scaffold without or with GA treatment, and SIS/PLA (Code No.3 ; 1 : 12 of salt content, (0.4 : 1 of SIS content, and 144 ${\mu}{\textrm}{m}$ of median pore size) without or with GA treatment were implanted into the back of nude mouse to observe the effect of SIS on the induction of cells proliferation by hematoxylin and eosin, and von Kossa staining for 8 weeks. It was observed that the effect of SIS/PLA scaffolds with GA treatment on bone induction are stronger than PLA scaffolds, that is to say, in the order of PLA/SIS scaffolds with GA treatment > PLA/SIS scaffolds without GA treatment > PGA nonwoven > PLA scaffolds only with GA treatment = PLA scaffolds only without GA treatment for the osteoinduction activity. The possible explanations are (1) many kinds of secreted, circulating, and extracellular matrix-bound growth factors from SIS to significantly affect critical processes of tissue development and differentiation, (2) the exposure of SIS to GA resulted in significantly calcification, and (3) peri-implant fibrosis due to covalent bonding between collagen molecule by crosslinking reaction. In conclusion, it seems that SIS plays an important role for bone induction in SIS/PLA scaffolds for the application of tissue engineering area.

The Effect of Solvents on Solid Dispersion of Ipriflavone with Polyvinylpyrrolidone In Vivo

Gilson Khang,Je Kyo Jeong,Yong San Ahn,Byung Kwan Moon,Myung Kyu Choi,John M. Rhee,Hai Bang Lee 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.1

Ipriflavone is a synthetic flavonoid derivate that improves osteoblast cell activity inhibiting bone resorption. In order to improve the bioavailability, solid dispersions of ipriflavone with PVP (poly-N- vinylpyrrolidone, MW=40,000 g/ mole) were prepared by a spray-drying method. During the manufacturing of solid dispersion, various solvents [ethanol (EtOH), acetonitrile, methylene chloride and cosolvent-EtOH:acetone=1:1] were used to dissolve the ipriflavone and PVP. Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were used to evaluate the physicochemical interaction between ipriflavone and PVP. Particle size, crystallinity and the area of the endotherm (∆H) of solid dispersed ipriflavone using the acetonitrile as solvent were much smaller than those of the other preparation types. Bioavailability of ipriflavone in vivo was changed by solvents. When considering the result of in vivo test, solid dispersion of ipriflavone using the acetonitrile as solvent showed the best choice.

Reduction of Inflammatory Responses and Enhancement of Extracellular Matrix Formation by Vanillin-Incorporated Poly(Lactic-<i>co</i>-Glycolic Acid) Scaffolds

Lee, Yujung,Kwon, Jeongil,Khang, Gilson,Lee, Dongwon Mary Ann Liebert 2012 Tissue engineering. Part A Vol.18 No.19

알긴산 나트륨이 장용코팅된 란소프라졸 제제의 저장안정성 및 용출률에 미치는 영향에 관한 연구

김정훈,오정민,강길선,정제교,이정식,정상영,이해방 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.4

Lansoprazole, pharmaceutics for acid-related diseases, is unstable in low pH environments and generally coated with enteric polymer to obtain gastroresistance in stomach. Because its storage stability is influenced by acidic substitutes of enteric polymer, alkaline chemicals were generally added to dosage form as a stabilizer. In this experience, we coated lansoprazole bead with sodium alginate and evaluated the effect of bead size and sodium alginate coating on the storage stability and dissolution profile of lansoprazole. Sodium alginate solution containing lansoprazole was sprayed as a droplet into 3% (w/v) CaCl_2 solution and the resultant bead was coated with starch, sodium alginate, and hydroxypropyl methylcellulose phthalate. The content of lansoprazole granule not coated with sodium alginate decreased to 57.96% of initial content when stored at a severe condition for 4 weeks, but that of lansoprazole granule coated with sodium alginate before enteric coating decreased little and as the thickness of sodium alginate film increased, the content of bead didn't decreased for 4 weeks. Sodium alginate film also improved the gastroresistance without much influencing the maximum dissolution rate.

멜라토닌이 함유된 다층 코팅 펠렛의 방출 및 특성분석

강복기,강길선,김종민,정상영,이해방,조선행 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.3

Melatonin (MT) is an indole amide pineal hormone. It has not only very short half-life but also pH-sensitive property. The sustained release dosage form which delivers M in a circadian fashion over 8 h is clinical value. The purpose of this study is to prepare sugar beads using multiple coating methods and enteric-coated in a sustained release to evaluate in vitro release characteristics in simulated gastric and intestinal fluids. The Eudragit^(?) as a polymer, sustained release membrance, and triethylcitrate (TEC) as a plasticizer were used. Multi-coated melatonin delivery system was composed of sugar, various excipients, Eudragit^(?) and enteric materials (e.g. hydorxy propyl methyl celluslose phthalate, HPMCP), and prepared by fluid bed coater. The dissolution test was carried out using the basket method at a stirring speed of 100 rpm at 37℃ in simulated gastric (pH 1.2) and intestinal fluid (pH 7.4). The released amount of MT was determined by High performance liquid chromatography method. The morphologies of surface and cross section of multi-coated beads were observed by scanning electron microscope. Size of multi-coated sugar beads was ranged over 1000∼1300 μm. The release rate of MT from coated beads was limited in simulated gastric fluid (pH 1.2), but it was sustained in intestinal fluid (pH 7.4) during 3∼8 hours. The MT beads may provide small-intestine-targeted device for oral delivery. Studies an animal and relative experiment are in process.

Recent advances in gold nanoparticle-based bioengineering applications

Kim, Eun Young,Kumar, Dinesh,Khang, Gilson,Lim, Dong-Kwon The Royal Society of Chemistry 2015 Journal of Materials Chemistry B Vol.3 No.43

<P>Plasmonic nanoparticle based nanotechnology plays a pivotal role in the recent advances in biomedical applications. Along with biocompatibility and robust surface chemistry, the tunable optical properties of the visible and near-infrared regions of gold nanoparticles have attracted significant attention for a wide range of biomedical applications such as<I>in vitro</I>biosensing,<I>in vivo</I>imaging, drug delivery, and tissue engineering. In this review, we focus on the the recent advances in biomedical applications based on the use of plasmonic nanoparticles, which have been developed to solve the limitations of current technologies in biosensing, bioimaging, therapeutic drug delivery, and tissue engineering applications.</P>

Kinin B1 Receptor Inhibition With BI113823 Reduces Inflammatory Response, Mitigates Organ Injury, and Improves Survival Among Rats With Severe Sepsis

Murugesan, Priya,Jung, Birgit,Lee, Dongwon,Khang, Gilson,Doods, Henri,Wu, Dongmei Oxford University Press 2016 The Journal of Infectious Diseases Vol.213 No.4

<P>Background. This study examined the therapeutic effects of an orally active nonpeptide kinin B1 receptor antagonist, BI113823, in a clinically relevant experimental model of polymicrobial sepsis in rats. Methods. Sepsis was induced by cecal ligation and puncture (CLP). Animals received treatment with either vehicle or BI113823. The experiment was terminated in the first set of animals 15 hours after CLP. Seven-day survival following CLP was determined in the second set of animals. Results. Compared with vehicle treatment, administration of BI113823 reduced neutrophil and macrophage infiltration, reduced cytokine production, attenuated intestinal mucosal hyperpermeability, prevented hemodynamic derangement, and improved cardiac output. Furthermore, administration of BI113823 reduced inducible nitric oxide synthase expression and the injury score in the lung and attenuated nuclear factor kappa B activation and apoptosis in the liver. Treatment with BI113823 also reduced plasma levels of cardiac troponin, aspartate aminotransferase, alanine aminotransferase, urea, and lactate, as well as proteinuria. Finally, administration of BI113823 improved the 7-day survival rate following CLP in rats. Conclusions. Administration of BI113823 reduced systemic and tissue inflammatory responses, prevented hemodynamic derangement, attenuated multiorgan injury, and improved overall survival.</P>

Multi-synergetic ZnO platform for high performance cancer therapy

Tripathy, Nirmalya,Ahmad, Rafiq,Ah Ko, Hyun,Khang, Gilson,Hahn, Yoon-Bong The Royal Society of Chemistry 2015 Chemical communications Vol.51 No.13

<P>ZnO platforms were evaluated for designing a high-performance anticancer drug (daunorubicin) carrier. Hollow structured ZnO, compared with nanorods, acts as a multi-purpose entity by serving as smart carriers and exhibiting synergetic photodynamic cytotoxic effects, which are ascribed to their high-specific surface area, hollow interior, pH-responsiveness and inherent photodynamism.</P> <P>Graphic Abstract</P><P>Hollow structured ZnO with high-performance drug-encapsulation for acid-triggered, chemo-photodynamic cancer therapy. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4cc10037a'> </P>

Enhanced <i>Ex Vivo</i> Expansion of Human Adipose Tissue-Derived Mesenchymal Stromal Cells by Fibroblast Growth Factor-2 and Dexamethasone

Lee, Sun-Young,Lim, Jiwon,Khang, Gilson,Son, Youngsook,Choung, Phil-Hoon,Kang, Shin-Sung,Chun, So Young,Shin, Hong-In,Kim, Shin-Yoon,Park, Eui Kyun Mary Ann Liebert 2009 Tissue engineering. Part A Vol.15 No.9

<P>In the present study, we investigated the ex vivo expansion of human adipose tissue-derived mesenchymal stromal cells (ATSCs) to identify factors that promoted efficient expansion while preserving stem cell potential. We examined several growth factors and steroids, and found that the combination of a low concentration of fibroblast growth factor-2 (FGF-2) (1 ng/mL) and dexamethasone (DEX) or betamethasone (BET) enhanced the proliferation of ATSCs by approximately 30-60% as compared to control. Enhanced proliferation under these conditions was confirmed using ATSCs isolated from three independent donors. ATSCs that were expanded in the presence of FGF-2 and DEX for 5 days were capable of differentiating into either osteoblastic or adipogenic cells, and the cells were positive for the mesenchymal stem cell markers such as CD29, CD44, CD90, CD105, and CD146, suggesting that the stem cell potential of the ATSCs was preserved. Analysis of signaling pathway revealed that tyrosine phosphorylation of Src kinase was dramatically increased in response to FGF-2 and DEX, suggesting the involvement of Src-dependent pathways in the stimulatory mechanism of proliferation of ATSCs by FGF-2 and DEX. Moreover, Src family kinase inhibitors (SU6656 and Src kinase inhibitor I) substantially reduced the FGF-2 and DEX-induced proliferation of ATSCs. SU6656 also inhibited the osteogenic and adipogenic differentiation of ATSCs. The results of the current study demonstrate that FGF-2 in combination with DEX stimulates the proliferation and osteoblastic and adipogenic differentiation of ATSCs through a Src-dependent mechanism, and that FGF-2 and DEX promote the efficient ex vivo expansion of ATSCs.</P>