Chi-Hwa Wang
Email Address
chewch@nus.edu.sg
Organizational Units
COLLEGE OF DESIGN & ENG
faculty
ENGINEERING
faculty
215 results
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Publication Sequential platelet-derived growth factor-simvastatin release promotes dentoalveolar regeneration(2014-01-01) Chang, P.-C.; Chong, L.Y.; Dovban, A.S.M.; Lim, L.P.; Lim, J.C.; Kuo, M.Y.-P.; Wang, C.-H.; DENTISTRY; CHEMICAL & BIOMOLECULAR ENGINEERINGObjectives: Timely augmentation of the physiological events of dentoalveolar repair is a prerequisite for the optimization of the outcome of regeneration. This study aimed to develop a treatment strategy to promote dentoalveolar regeneration by the combined delivery of the early mitogenic factor platelet-derived growth factor (PDGF) and the late osteogenic differentiation factor simvastatin. Materials and Methods: By using the coaxial electrohydrodynamic atomization technique, PDGF and simvastatin were encapsulated in a double-walled poly(d,l-lactide) and poly(d,l-lactide-co- glycolide) (PDLLA-PLGA) microspheres in five different modes: microspheres encapsulating bovine serum albumin (BB), PDGF alone (XP), simvastatin alone (SB), PDGF-in-core and simvastatin-in-shell (PS), and simvastatin-in-core and PDGF-in-shell (SP). The microspheres were characterized using scanning electronic microscopy, and the in vitro release profile was evaluated. Microspheres were delivered to fill large osteotomy sites on rat maxillae for 14 and 28 days, and the outcome of regeneration was evaluated by microcomputed tomography and histological assessments. Results: Uniform 20-μm controlled release microspheres were successfully fabricated. Parallel PDGF-simvastatin release was noted in the PS group, and the fast release of PDGF followed by the slow release of simvastatin was noted in the SP group. The promotion of osteogenesis was observed in XP, PS, and SP groups at day 14, whereas the SP group demonstrated the greatest bone fill, trabecular numbers, and thickest trabeculae. Bone bridging was evident in the PS and SP group, with significantly increased osteoblasts in the SP group, and osteoclastic cell recruitment was promoted in all bioactive molecule-treated groups. At day 28, osteogenesis was promoted in all bioactive molecule-treated groups. Initial corticalization was noted in the XP, PS, and SP groups. Osteoblasts appeared to be decreased in all groups, and significantly, a greater osteoclastic cell recruitment was noted in the SB and SP groups. Conclusions: Both PDGF and simvastatin facilitate dentoalveolar regeneration, and sequential PDGF-simvastatin release (SP group) further accelerated the regeneration process through the enhancement of osteoblastogenesis and the promotion of bone maturation. © Copyright 2014, Mary Ann Liebert, Inc.Publication Paclitaxel and suramin-loaded core/shell microspheres in the treatment of brain tumors(2010-11) Nie, H.; Fu, Y.; Wang, C.-H.; CHEMICAL & BIOMOLECULAR ENGINEERINGThis work presents a modified method, namely coaxial electrohydrodynamic atomization, for the preparation of microspheres with distinct core/shell structures. This allows the encapsulation of two drugs with different characteristics in hydrophilic properties in one single step. Variation of ratios between outer flow and inner flow produces polymer microspheres with different core/shell ratios, and consequently results in variable release rates of drugs. Significant changes in release patterns were demonstrated when the distributions of the two drugs in microspheres were swapped. Moreover, cell culture experiments and animal experiments have been carried out to testify the performances of different microspheres in cytotoxicity, cellular apoptosis in vitro and tumor inhibition against subcutaneous U87 glioma xenograft in BALB/c nude mice. These findings present the advantages and possible application of this kind of multi-drug release system in treating brain tumors. Moreover, the release rates and characteristic sequences of multi-drugs can be tailored and tuned according to treatment necessity and applied in treating other kinds of tumors. © 2010 Elsevier Ltd.Publication Bioaugmentation of Methanosarcina thermophila grown on biochar particles during semi-continuous thermophilic food waste anaerobic digestion under two different bioaugmentation(2022-09-01) Jonathan TE Lee; Nalok Dutta; Le Zhang; Thomas TH Tsui; Shuhan Lim; Zhi Kai Tio; Ee Yang Lim; Jiachen Sun; Jingxin Zhang; Chi-Hwa Wang; Yong Sik Ok; Birgitte K Ahring; Yen Wah Tong; CHEMICAL AND BIOMOLECULAR ENGINEERING; NUS ENVIRONMENTAL RESEARCH INSTITUTEPublication Controlled release of human immunoglobulin G. 1. Release kinetics studies(1999-02) Wang, C.-H.; Sengothi, K.; Lee, T.; CHEMICAL & ENVIRONMENTAL ENGINEERINGThe release of human immunoglobulin G (IgG) using ethylene-vinyl acetate copolymer (EVAc) as a polymer carrier was studied by fabricating them into two commercially available dosage forms: slab and microsphere. A first-order flux decay model and two hierarchical models concerned with the mass transfer coefficient on the slab surface were used to describe the mechanism of release kinetics and the results compared. These models gave insight to some of the important physical parameters of drug release such as the diffusion coefficient, time constant of release, and initial flux. It was found that the release mechanism varies with time, and hence no single model can be used to predict the release profile for the entire period of study. A controlled release study by matrix coating was also done. The results obtained were utilized to examine the suitability of a particular dosage form (matrix geometry) of IgG for clinical applications. The release data compared with the standard methods of IgG therapy proves localized drug delivery to be a major boon for immunodeficient patients.Publication Jet breakup and droplet formation in near-critical regime of carbon dioxide-dichloromethane system(2008-07) Lee, L.Y.; Lim, L.K.; Hua, J.; Wang, C.-H.; CHEMICAL & BIOMOLECULAR ENGINEERINGThe jet breakup and droplet formation mechanism of a liquid in the near-critical conditions of a solvent-antisolvent system is examined with high-speed visualization experiments and simulated using a front tracking/finite volume method. The size of droplets formed under varying system pressure at various jet breakup regimes is measured with a Global Sizing Velocimetry, using the shadow sizing method. A stainless steel nozzle with 0.25 mm I.D and 1.6 mm O.D was used in this study. Experiments were performed at fixed temperature of 35 °C and system pressure in the range from 61 to 76 bar in the near-critical regime of the DCM-CO2. At the near mixture critical regime for DCM-CO2 mixture, the miscibility between the two fluid phases increases and the interfacial tension diminishes. This phase behavior has important applications in particle formation using gas antisolvent (GAS) and supercritical antisolvent (SAS) processes. The jet breakup and droplet formation in the near-critical regime is strongly dependent on the changes in interface tension and velocity of the liquid phase. An understanding of the droplet formation and jet breakup behavior of DCM-CO2 in this regime is useful in experimental design for particle fabrication using SAS method. © 2008 Elsevier Ltd. All rights reserved.Publication Electrospun micro- and nanofibers for sustained delivery of paclitaxel to treat C6 glioma in vitro(2006-08) Xie, J.; Wang, C.-H.; CHEMICAL & BIOMOLECULAR ENGINEERINGPurpose. The present study aims to develop electrospun PLGA-based micro- and nanofibers as implants for the sustained delivery of anticancer drug to treat C6 glioma in vitro. Methods. PLGA and an anticancer drug-paclitaxel-loaded PLGA micro- and nanofibers were fabricated by electrospinning and the key processing parameters were investigated. The physical and chemical properties of the micro- and nanofibers were characterized by various state-of-the-art techniques, such as scanning electron microscope and field emission scanning electron microscope for morphology, X-ray photoelectron spectroscopy for surface chemistry, gel permeation chromatogram for molecular weight measurements and differential scanning calorimeter for drug physical status. The encapsulation efficiency and in vitro release profile were measured by high performance liquid chromatography. In addition, the cytotoxicity of paclitaxel-loaded PLGA nanofibers was evaluated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide MTT) assay on C6 glioma cell lines. Results. PLGA fibers with diameters of around several tens nanometers to 10 μm were successfully obtained by electrospinning. Ultrafine fibers of around 30 nm were achieved after addition of organic salts to dilute polymer solution. The encapsulation efficiency for paclitaxel-loaded PLGA micro- and nanofibers was more than 90%. DSC results suggest that the drug was in the solid solution state in the polymeric micro- and nanofibers. In vitro release profiles suggest that paclitaxel sustained release was achieved for more than 60 days. Cytotoxicity test results suggest that IC50 value of paclitaxel-loaded PLGA nanofibers (36 μg/ml, calculated based on the amount of paclitaxel) is comparable to the commercial paclitaxel formulation-Taxol®. Conclusions. Electrospun paclitaxel-loaded biodegradable micro- and nanofibers may be promising for the treatment of brain tumour as alternative drug delivery devices. © 2006 Springer Science + Business Media, Inc.Publication Combined modality doxorubicin-based chemotherapy and chitosan-mediated p53 gene therapy using double-walled microspheres for treatment of human hepatocellular carcinoma(2013-07) Xu, Q.; Leong, J.; Chua, Q.Y.; Chi, Y.T.; Chow, P.K.H.; Pack, D.W.; Wang, C.-H.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE; CHEMICAL & BIOMOLECULAR ENGINEERINGThe therapeutic efficiency of combined chemotherapy and gene therapy on human hepatocellular carcinoma HepG2 cells was investigated using double-walled microspheres that consisted of a poly(d,. l-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(l-lactic acid) (PLLA) shell layer and fabricated via the precision particle fabrication (PPF) technique. Here, double-walled microspheres were used to deliver doxorubicin (Dox) and/or chitosan-DNA nanoparticles containing the gene encoding the p53 tumor suppressor protein (chi-p53), loaded in the core and shell phases, respectively. Preliminary studies on chi-DNA nanoparticles were performed to optimize gene transfer to HepG2 cells. The transfection efficiency of chi-DNA nanoparticles was optimal at an N/P ratio of 7. In comparison to the 25-kDa branched polyethylenimine (PEI), chitosan showed no inherent toxicity towards the cells. Next, the therapeutic efficiencies of Dox and/or chi-p53 in microsphere formulations were compared to free drug(s) and evaluated in terms of growth inhibition, and cellular expression of tumor suppressor p53 and apoptotic caspase 3 proteins. Overall, the combined Dox and chi-p53 treatment exhibited enhanced cytotoxicity as compared to either Dox or chi-p53 treatments alone. Moreover, the antiproliferative effect was more substantial when cells were treated with microspheres than those treated with free drugs. High p53 expression was maintained during a five-day period, and was largely due to the controlled and sustained release of the microspheres. Moreover, increased activation of caspase 3 was observed, and was likely to have been facilitated by high levels of p53 expression. Overall, double-walled microspheres present a promising dual anticancer delivery system for combined chemotherapy and gene therapy. © 2013 Elsevier Ltd.Publication Experimental and numerical investigations on the electrostatics generation and transport in the downer reactor of a triple-bed combined circulating fluidized bed(2012-10-31) Cheng, Y.; Lau, D.Y.J.; Guan, G.; Fushimi, C.; Tsutsumi, A.; Wang, C.-H.; CHEMICAL & BIOMOLECULAR ENGINEERINGElectrostatics is an inevitable phenomenon in fluidization processes and granular flow systems where collisions between particulates and walls with different materials occur. In this study, the electrostatic performance in the downer reactor of a triple-bed combined circulating fluidized bed was investigated through both experiments and numerical simulations. In numerical simulation the Discrete Element Method (DEM) was adopted to simulate the electrostatic charge generation and transfer occurring in the downer. Both experimental and numerical results showed that the averaged induced currents caused by electrostatics increased with increasing solids mass flux in the downer, and the electrostatics was the strongest near the entrance of the downer because of the highest frequency of collisions between particles and the wall caused by the largest solids holdup at that location. Numerical studies also revealed that the averaged induced currents increased with increasing initial particle velocity and particle size, and the averaged induced current caused by the charge transfer was much larger than those by charge generation through tribocharging. These results may help us better understand the mechanism of electrostatic phenomena, and better cope with challenges and problems caused by electrostatics. © 2012 American Chemical Society.Publication Gentamicin-loaded discs and microspheres and their modifications: Characterization and in vitro release(2005-02-02) Naraharisetti, P.K.; Ning Lew, M.D.; Fu, Y.-C.; Lee, D.-J.; Wang, C.-H.; SINGAPORE-MIT ALLIANCE; CHEMICAL & BIOMOLECULAR ENGINEERINGOsteomyelitis is an infection of the bone, and successful treatment involves local administration for about 6 weeks. Gentamicin is a very hydrophilic drug and tends to come out into the water phase when microspheres are fabricated using solvent evaporation method. Hence, spray drying is an option, and it was observed that the release rate tends to be fast when the particle size is small and large particles cannot be prepared by spray drying. In an effort to get better encapsulation efficiency and release rate, we have worked on the possibility of compressing the microspheres into discs and modifying the porosity of the discs by using biocompatible materials like polyethylene glycol (PEG) and calcium phosphates and also on the fabrication of double-walled and composite microspheres. In the case of microspheres, two methods of fabrication both based on solvent evaporation method were employed. The two polymers used are poly-l-lactide (PLLA) and copolymers of poly-dl-lactic-co-glycolic acid (PLGA). One method is based on the spreading coefficient theory for the formation of double-walled microspheres by using single solvent, while the other is based on the property of PLLA not being soluble in ethyl acetate (EA). Characterization to check if the microspheres formed are double-walled was performed. The fabrication method where two solvents, dichloromethane (DCM) and ethyl acetate, were used gave double-walled microspheres, while the other where only dichloromethane was used gave composites. The double-walled microspheres were smaller in size compared to the composites, which were in the range of 100-600 μm. This can be attributed to the difference in the fabrication procedure. We were able to achieve better encapsulation efficiencies of more than 50% and slower release rates, which lasted for about 15 days. It was observed that size played a major role in the encapsulation efficiency and release rates. The possibility of achieving better results by studying the effect of concentration of polymer in solvent and the effect of using different polymers was investigated. © 2004 Elsevier B.V. All rights reserved.Publication Numerical study on coal gasification in the downer reactor of a triple-bed combined circulating fluidized bed(2014-04-23) Cheng, Y.; Wang, C.-H.; CHEMICAL & BIOMOLECULAR ENGINEERINGOwing to the advantages of cocurrent gas-solids flow without back mixing, short residence time, and uniform residence time distribution, the downer has emerged as an ideal reactor for gasification with high selectivity. In this study, the coal gasification in the down reactor of a triple-bed combined circulating fluidized bed was studied through computation fluid dynamics simulations using an Eulerian-Lagrangian method. The influences of nozzle arrangement for coal feeding, coal particle, and air/steam/coal feeding rates on the gasification were investigated. It was found that the tangential arrangement of feeding resulted in comparable H2 production with the normal arrangement, and higher CO production. When coal particle size was smaller than 500 μm, the particle size had little influence on the produced gas composition. In contrast, with increasing particle size beyond 500 μm, coal particles could not be gasified completely due to shorter residence time, leading to decreasing production of CO and H2. Steam gasification had a higher volume fraction of CO and H2, as well as higher char conversion ratio. With increasing coal feeding rates, the volume fraction of CO increased monotonically, while that of H2 increased first and then approached a constant value due to limited moisture availability in the coal samples. With increasing air feeding rates, more char and volatiles could be decomposed into light gases. As a result, the volume fraction of CO increased first and then started to decrease. These results had great significance in designing a better downer reactor with improved efficiency. © 2014 American Chemical Society.