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Singapore HEALTH Award (Gold) 2008 and 2010

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RESEARCH AREAS > Cell and Tissue Engineering

Cell and Tissue Engineering

Cell and Tissue Engineering, where biomimicking materials, stem cell technology, microfluidic systems and bioimaging tools are combined to develop novel approaches to regenerative medicine and artificial organs.

View research projects, research publications and research staff in this research area.

Research Projects

1. Collagen-Apatite Nanofoams as Bone Implants for Load-Bearing Applications

Shona Pek, Shujun Gao, Shariff Arshad and Jackie Y. Ying

Large amounts of lost bone are usually replaced by a variety of grafts or permanent alloy implants. The aim of this project is to create a composite bone scaffold material that has sufficient strength to support patients' lifestyles, and bioactivity to promote cell attachment and proliferation. This scaffold would be resorbable by natural tissue, with tunable mechanical properties and degradation rates. Two research challenges are the introduction of macroporosity and mechanical strength for load-bearing applications. IBN's research strategy involves creating a nanocomposite foam of collagen fibers and apatite nanocrystals. Preliminary in vitro studies with MC3T3 osteoblast cells indicate excellent cell attachment and proliferation on this scaffold. Ectopic in vivo implantation on SCID mice shows evidence of bone, tissue and blood vessel formation in the scaffold material. In addition, in vivo implantation of this scaffold material into critical-sized defects in the femur of Wistar rat and the tibia of Yorkshire-Landrace pigs resulted in successful healing and functioning of the defect area without the need for an external supporting cast.

2. Development of a Bioartificial Kidney

Farah Tasnim, Yar Oo Zay, Mohammed Shahrudin Ibrahim, Ming Ni, Daniele Zink and Jackie Y. Ying

Commercialized in 1956, hemodialysis has been widely used to treat patients suffering from chronic renal failure. With hemodialysis, millions of renal failure patients in the world have not only survived, but also successfully demonstrated certain levels of social activities. However, hemodialysis is still inefficient as a renal replacement therapy. It only provides intermittent blood filtration and is unable to replicate the important absorptive, metabolic, endocrine, and immunological functions of the natural kidney. At IBN, we are developing an extracorporeal filtration and reclamation device consisting of composite hollow fibers made at IBN. This portable device will be able to continuously remove excess water and toxic wastes from the blood. By incorporating living epithelial cells of the kidney proximal tubule into the hollow fibers, the device will also be able to provide certain functions that are absent in conventional hemodialysis. As a result, the quality of life of the renal patients could be significantly improved by this biomedical device.

3. Digital Livers

Dean Tai, Alvin Kang, Yuting He, Shuoyu Xu, Baixue Zheng, Qiwen Peng and Hanry Yu

We have developed optical imaging modalities to quantify liver fibrosis in tissues. The instruments and image-processing/feature analysis algorithms developed are being applied to automate and improve the pathological examinations related to fibrosis (FIBRO-C INDEX), and cancer-stroma interactions, which shed lights into the etiology of the diseases in quantitative manners. We are also developing a high throughput tissue imaging platform to quantify tissue/cell and ECM features of the whole organ in mice or the entire biopsy sample at molecular and cell resolutions. We are establishing the molecular and cellular basis of clinical imaging modalities such as MRI through the high resolution organ imaging of disease models. We utilize these quantitative tissue imaging modalities, and have also developed high-content analysis platform to be interfaced with robot-based liquid handling systems to evaluate efficacy of compounds against liver fibrosis in vitro and in vivo.

4. Drug Testing Platforms

Abhishek Ananthanarayanan, Ciprian Iliescu, Deepak Choudhury and Hanry Yu

Cell-based assays for evaluation of the hepatotoxicity are attracting increasing attention from institutions and companies undertaking drug development. The major bottlenecks in employing these assays reside primarily in the lack of stable human hepatocytes as well as cell-culture models that recapitulate the in vivo physiological responses to the tested compounds. Academically, many cell-based models have been proposed with the promising ones based on sandwich, spheroid, and co-culture. So far, only the sandwich model is accepted by the Federal Drug administration (FDA) for routine hepatotoxicity testing of drugs. To improve the cell-based assays, we have developed 1) a much improved sandwich model, 2) a much improved spheroid model, 3) a culture supplement that substitutes the role of co-culture, and 4) three perfusion-based models. We are evaluating the strengths and limitations of these models in hepatotoxicity testing of paradigm compounds and improving the performance of these platforms for throughput. We also are developed microfluidic chips to predict the physiology-based pharmacokinetics properties of compounds.

5. Engineering Complex Tissues with Spatial and Temporal Control of Micro-Environmental Cues (Micro-Tissue Fabrication Factory)

Bramasta Nugraha, Cipian Iliescu and Hanry Yu

Complex tissues with multiple cell types will be engineered by controlling cell-cell interactions through manipulating cell-surface molecules, delivering growth factors precisely with controlled delivery devices, engineering cellular response to the chemical and mechanical signals using suitable hydrogels, and fabricating relevant 3D microfluidics and networks of channels. This project integrates biomaterials and novel microfabrication technologies to generate precisely controlled cell-containing structures that preserve the functions of liver cells as prototype microliver tissues. This project establishes the fundamental principles, toolboxes and devices to precision-engineer complex tissues and interfaces for drug testing and therapeutic applications.

6. Epigenetic Mechanisms of Gene Regulation and the Spatial Organization of Gene Loci in the Cell Nucleus

Karthikeyan Kandasamy and Daniele Zink

The transcriptional activity of mammalian genes is regulated by a complex network of multiple variables. These include the binding of transcriptional regulators to cis-regulatory DNA elements as, for example, enhancer elements and promoters. In addition, epigenetic mechanisms involving DNA methylation, histone modifications, and the spatial organization of gene loci in the nucleus contribute to the transcriptional regulation of gene loci. Currently, it is unclear how the different levels of regulation interact and become integrated. Furthermore, it is not understood how the spatial organization of gene loci in the nucleus is regulated. Experimental evidence obtained during our previous studies suggested that the patterns of histone modifications not only regulate local chromatin structure, but also impact the spatial positioning of gene loci. These studies used the human cystic fibrosis gene (CFTR) and adjacent genes as model system. Using high-resolution light microscopy and ChIP/chip analyses, we will further explore this model system in order to address the functional relationships between the regulation of gene-specific patterns of histone modifications and the regulation of the nuclear positioning of corresponding loci.

7. Fibrous Scaffolds for Tissue Engineering

Benjamin Tai, Shona Pek, Karthikeyan Narayanan, Chan Du, James Hsieh, Meng Fatt Leong, Jerry Toh, Serina Ng, Hongfang Lu, Andrew Wan and Jackie Y. Ying

Tissue engineering requires the use of a structural framework to support the adhesion and growth of cells. In addition to acting as a structural template, scaffolds provide the opportunity for the presentation of biological molecules that regulate the proliferation and differentiation of cells into tissue structures. This is especially important in conjunction with the use of stem and progenitor cells. Most of the current processes for the production of tissue scaffolds are incompatible with the incorporation of biological molecules, specifically proteins, due to the severity of conditions involving the use of high temperatures and organic solvents. We are developing procedures for making scaffolds by polyelectrolyte complexation, which is inherently more suitable for the presentation of biologics due to the milder, aqueous-based synthesis. The characteristics of these scaffolds are optimized to capitalize on the activity of various biological factors with respect to tissue development. By culturing differentiated embryonic and mesenchymal stem cells on these scaffolds, we are working towards therapies for liver failure and diabetes Type I. Another important effort in our group is the development of 3D matrices, to more closely mimic the natural environment of the cell for in vitro models.

8. Magnetic Nanoparticles and Quantum Dots for Cell Separation and Imaging

Nandanan Erathodiyil, Yong Wang, Karthikeyan Narayanan and Jackie Y.

Cell separation has become an essential tool for a wide variety of biomedical applications. It is important to attain high-purity cell populations of interest from mixed cell populations for use in therapeutics and diagnostics. Antibodies can serve as molecules targeting specific membrane proteins on certain cell types. Our approach in cell separation was achieved by utilizing targeting ligands with magnetic nanoparticles and quantum dots. We have used glucosamine in the separation of insulin-secreting beta cells. The differential binding affinity of Glut2 towards glucosamine is employed to target and separate insulin-secreting beta cells from a mixed population of cells. Cell sorting was achieved by magnetic cell manipulation or FACS. We are currently developing a variety of small molecules to target other cell types such as neurons.

9. Sandwich-Culture Based Applications

Xia Lei, Yan Wang, Wenhao Tong, and Hanry Yu

We have developed a greatly improved sandwich culture based on synthetic membranes and novel laminar-flow bioreactors at mini- or micro-scales. Controlling the mass transfer properties through these membranes and the environments to stimulate cellular functions, we are scaling these culture configurations into a higher throughput system for drug testing applications; and applying it to develop a renewable hybrid liver device to support patients with liver failure, at reduced cost and improved effectiveness. The key feature of these cultures are their abilities to maintain hepatocyte polarity and enhance secretory functions that allow the devices to be regenerated after exposure to toxic substances in patients with failed liver.

10. Three-Dimensional Cell Culture Using Two-Photon Stereolithography

James T. M. Hsieh, Karthikeyan Narayanan, Meng Fatt Leong, Jerry Toh, Andrew Wan and Jackie Y. Ying

It has been discovered that cells behave differently in a flat layer than in complex, three-dimensional tissue. Cell studies in 3D may be more physiologically relevant as the 3D environment more closely resembles living tissue. However, few existing methods have been able to provide the required degree of control to spatially pattern cells in 3D. IBN is developing various new bioartificial devices using the 2-photon stereolithography laser system. These new devices are designed to closely resemble the natural cell architecture by incorporating biochemical cues onto material surfaces. In addition, these miniaturized devices are made from biodegradable materials, thus offering the potential for implantation.

Research Publications

  1. A. Lakshmanan, S. Zhang and C. A. E. Hauser, "Short Self-Assembling Peptides as Building Blocks for Modern Nanodevices," Trends in Biotechnology, (2011) DOI: 10.1016/j.tibtech.2011.11.001

  2. H. F. Lu, K. Narayanan, S-X Lim, S. Gao, M. F. Leong and A. C. A. Wan, "A 3D Microfibrous Scaffold for Long-Term Human Pluripotent Stem Cell Self-Renewal Under Chemically Defined Conditions," Biomaterials, (2011) DOI: 10.1016/j.biomaterials.2011.11.077

  3. E. C. Wu, S. Zhang and C. A. E. Hauser, "Self-Assembling Peptides as Cell-Interactive Scaffolds," Advanced Functional Materials, (2011) DOI: 10.1002/adfm.201101905

  4. L. Xia, R. B. Sakban, Y.Qu, X. Hong, W. Zhang, B. Nugraha, W. H. Tong, A. Ananthanarayanan, B. Zheng, I. Y-Y Chau, R. Jia, M. McMillian, J. Silva, S. Dallas and H. Yu, "Tethered Spheroids as an In Vitro Hepatocyte Model for Drug Safety Screening," Biomaterials, (2011) DOI: 10.1016/j.biomaterials.2011.12.006

  5. A. C. A. Wan, M. F. Leong, J. K. C. Toh, Y. Zheng and J. Y. Ying, "Multicomponent Fibers by Multi-Interfacial Polyelectrolyte Complexation," Advanced Healthcare Materials, (2011) DOI: 10.1002/adhm.201100020

  6. D. Choudhury, D. v. Noort, C. Iliescu, B. Zheng, K-L. Poon, S. Korzh, V. Korzh and H. Yu, "Fish and Chips: A Microfluidic Perfusion Platform For Monitoring Zebrafish Development," Lab on a Chip, (2011) DOI: 10.1039/c1lc20351g

  7. T. M. Hsieh, A. C. A. Wan and J. Y. Ying, "Applications of Fabricated Micro- and Nanostructures in Biomedicine," MRS Bulletin, 36 (2011) 990-997

  8. J Lin, F. Lu, W. Zheng, S. Xu, D. Tai, H. Yu and Z. Huang, "Assessment of Liver Steatosis and Fibrosis in Rats Using Integrated Coherent Anti-Stokes Raman Scattering and Multiphoton Imaging Technique," Journal of Biomedical Optics, 16 (2011) 116024

  9. R. Magalhães, B. Nugraha, S. Pervaiz, H. Yu and L. L. Kuleshova, "Influence of Cell Culture Configuration on the Post-Cryopreservation Viability of Primary Rat Hepatocytes," Biomaterials, 33 (2011) 829-836

  10. B. Zheng, L. Tan, X. Mo, W. Yu, Y. Wang, L.Tucker-Kellogg, R. E. Welsch, P. T. C. So and H. Yu, "Predicting In Vivo Anti-Hepatofibrotic Drug Efficacy Based on In Vitro High-Content Analysis," PLoS ONE, 6 (2011) e26230

  11. Y. C. Toh, K. Blagovic, H. Yu and J. Voldman, "Spatially Organized In Vitro Models Instruct Asymmetric Stem Cell Differentiation," Integrative Biology, 3 (2011) 1179-1187

  12. F. Zhuang, K. Oglecka and C. A. E. Hauser, "Self-Assembling Peptide Surfactants A6K and A6D Adopt α-Helical Structures Useful for Membrane Protein Stabilization," Membranes, 1 (2011) 314-326

  13. M. Ni, P. K. Zimmermann, K. Kandasamy, W. Lai, Y. Li, M. F. Leong, A. C. A. Wan and D. Zink, "The Use of a Library of Industrial Materials to Determine the Nature of Substrate-Dependent Performance of Primary Adherent Human Cells," Biomaterials, 33 (2011) 353-364

  14. Y. Loo, S. Zhang and C. A. E. Hauser, "From Short Peptides to Nanofibers to Macromolecular Assemblies in Biomedicine," Biotechnology Advances, (2011) DOI: 10.1016/j.biotechadv.2011.10.004

  15. L. Venkatraman, H. Li, C. F. Dewey, J. K. White, S. S. Bhowmick, H. Yu and L. Tucker-Kellogg, "Steady States and Dynamics of Uurokinase-Mediated Plasmin Activation In Silico and In Vitro," Biophysical Journal, 101 (2011) 1825-1834

  16. A. Lakshmanan and C. A. E. Hauser, "Ultrasmall Peptides Self-Assemble into Diverse Nanostructures: Morphological Evaluation and Potential Implications," International Journal of Molecular Sciences, 12 (2011) 5736-5746

  17. Y. O. Zay, R. Deng, M. Hu, M. Ni, K. Kandasamy, M. S. bin Ibrahim, J. Y. Ying and D. Zink, "The Performance of Primary Human Renal Cells in Hollow Fiber Bioreactors for Bioartificial Kidneys," Biomaterials, 32 (2011) 8806-8815

  18. F. Tasnim, K. Kandasamy, J. S. Muck, M. S. bin Ibrahim, J. Y. Ying and D. Zink, "Effects of BMPs on Primary Human Renal Cells and the Generation of BMP-7-Expressing Cells for Applications in Bioartificial Kidneys," Tissue Engineering, Part A (2011)

  19. S. L. J. Ng, K. Narayanan, S. Gao and A. C. A. Wan, "Lineage Restricted Progenitors for the Repopulation of Decellularized Heart," Biomaterials, 32 (2011) 7571-7580

  20. E. Tamariz, A. C. A. Wan, Y. S. Pek, M. Giordano, G. Hernández-Padrón, A. Varela-Echavarría, I. Velasco and V. M. Castaño, "Delivery of Chemotropic Proteins and Improvement of Dopaminergic Neuron Outgrowth Through a Thixotropic Hybrid Nano-Gel," Journal of Materials Science: Materials in Medicine, 22 (2011) 2097-2109

  21. B. Nugraha, X. Hong, X. Mo, L. Tan, W. Zhang, P-M. Chan, C. H. Kang, Y. Wang, L. T. Beng, W. Sun, D. Choudhury, J. M. Robens, M. McMillian, J. Silva, S. Dallas, C-H. Tan, Z. Yue and H. Yu, "Galactosylated Cellulosic Sponge for Multi-Well Drug Safety Testing," Biomaterials, 32 (2011) 6982-6994

  22. Y. S. Pek and A. C. A. Wan, "Characterization of Early Extracellular Matrix Secretions in a Three-Dimensional Thixotropic Cell Culture System," Acta Biomaterialia, 7 (2011) 3981-3987

  23. D. Choudhury, X. Mo, C. Iliescu, L. L. Tan, W. H. Tong and H. Yu, "Exploitation of Physical and Chemical Constraints for Three-Dimensional Microtissue Construction in Microfluidics," Biomicrofluidics, 5 (2011) 22203

  24. A. Mishra, Y. Loo, R. Deng, Y. J. Chuah, H. T. Hee, J. Y. Ying and C. A. E Hauser, "Ultrasmall Natural Peptides Self-Assemble to Strong Temperature-Resistant Helical Fibers in Scaffolds Suitable for Tissue Engineering," Nano Today, 6 (2011) 232-239

  25. Y. Li, Y. Zheng, K. Zhang, J. Y. Ying and D. Zink, "Effects of Quantum Dots on Different Renal Proximal Tubule Cell Models and on Gel-Free Renal Tubules Generated In Vitro," Nanotoxicology, (2011) DOI: 10.3109/17435390.2011.562326

  26. J. ZHou, C. Bi, W.-J. Chng, L.-L. Cheong, S.-C. Liu, S. Mahara, K.-G. Tay, Q. Zeng, J. Li, K. Guo, C. P. B. Tan, H. Yu, D. H. Albert and C.-S. Chen, "PRL-3, A Metastasis Associated Tyrosine Phosphatase, is Involved in FLT3-ITD Signaling and Implicated in Anti-AML Therapy," PLoS ONE, 6 (2011) e19798

  27. B. Jakob, J, Splinter, S. Conrad, K.-O. Voss, D. Zink, M. Durante, M. Loebrich and G. Taucher-Scholz, "DNA Double-Strand Breaks in Heterochromatin Elicit Fast Repair Protein Recruitment, Histone H2AX Phosphorylation and Relocation to Euchromatin," Nucleic Acids Research, 39 (2011) 6489-6499

  28. K. Subramaniam, K. Kandasamy, K. Joseph, E. K. Spicer and B. G. Tholanikunnel, "3'-Untranslated Region Length and AU-Rich RNA Location Modulate RNA-Protein Interaction and Translational Control of β2-Adrenergic Receptor mRNA," Molecular and Cellular Biochemistry, 352[1-2] (2011) 125-141(17)

  29. K. Subramaniam, K. Kandasamy, K. Joseph, E. K. Spicer and B. G. Tholanikunnel, "3'-Untranslated Region Length and AU-Rich RNA Location Modulate RNA-Protein Interaction and Translational Control of β2-Adrenergic Receptor mRNA," Molecular and Cellular Biochemistry, 352 (2011) 125-141

  30. Z. Ding, Y. Kng, H. Yang, Z. Ke and L. Zhuo, "An Orally Available Small Imidazolium Salt Ameliorates Inflammation and Fibrosis in a Murine Model of Cholestasis," Laboratory Investigation, 91 (2011) 752-763

  31. Z. Ding, Y. Kng, H. Yang, Z. Ke and L. Zhuo, "An Orally Available Small Imidazolium Salt Ameliorates Inflammation and Fibrosis in a Murine Model of Cholestasis," Laboratory Investigation, 91 (2011) 752-763

  32. B. Gopalan, Z. Ke, C. Zhang, Y. Kng, N. A. Suhaimi, S. N. Riduan, Y. Zhang and L. Zhuo, "Metal-Free Imidazolium Salts Inhibit the Growth of Hepatocellular Carcinoma in a Mouse Model," Laboratory Investigation, 91 (2011) 744-751

  33. B. Gopalan, Z. Ke, C. Zhang, Y. Kng, N-A. Suhaimi, S. N. Riduan, Y. Zhang and L. Zhuo, "Metal-Free Imidazolium Salts Inhibit the Growth of Hepatocellular Carcinoma in a Mouse Model," Laboratory Investigation, 91 (2011) 744-751

  34. S. Kumar and L. Zhuo, "Quantitative Analysis of Pupillary Light Reflex by Real-Time Autofluorescent Imaging in a Diabetic Mouse Model," Experimental Eye Research, 92[3] (2011) 4-172

  35. S. Kumar and L. Zhuo, "Quantitative Analysis of Pupillary Light Reflex by Real-Time Autofluorescent Imaging in a Diabetic Mouse Model," Experimental Eye Research, 92 (2011) 164-172

  36. D. Berchtold, S. Fesser, G. Bachmann, A. Kaiser, J. C. Eilert, F. Frohns, N. Sadoni, J. Muck, E. Kremmer, D. Eick, P. G. Layer and D. Zink, "Nuclei of Chicken Neurons in Tissues and Three-Dimensional Cell Cultures are Organized into Distinct Radial Zones," Chromosome Research, 19[2] (2011) 165-182

  37. D. Berchtold, S. Fesser, G. Bachmann, A. Kaiser, J. C. Eilert, F. Frohns, N. Sadoni, J. Muck, E. Kremmer, D. Eick, P. G. Layer and D. Zink, "Nuclei of Chicken Neurons in Tissues and Three-Dimensional Cell Cultures are Organized into Distinct Radial Zones," Chromosome Research, 19 (2011) 165-182

  38. C. Anene-Nzelu, Y. Wang, H. Yu and H. L. Leo, "Liver Tissue Model for Drug Toxicity Screening," Journal of Mechanics in Medicine and Biology, 2 (2011) 369-390

  39. M. Ni, J. C .M. Teo, M. S. bin Ibrahim, K. Zhang, F. Tasnim, P.-Y. Chow, D. Zink and J. Y. Ying, "Characterization of Membrane Materials and Membrane Coatings for Bioreactor Units of Bioartificial Kidneys," Biomaterials, 32[6] (2010) 1465-1476

  40. A. Ananthanarayanan, B. C. Narmada, X. Mo, M. McMillian and H. Yu, "Purpose-Driven Biomaterials Research in Liver Tissue Engineering," Trends in Biotechnology, 29[3] (2010) 110-118

  41. J. Yang, J. Y. Lee and J. Y. Ying, "Phase Transfer and Its Applications in Nanotechnology," Chemical Society Reviews, 40[3] (2010) 1672-1696

  42. X. Zhang, Y. H. Tee, J. K. Heng, Y. Zhu, X. Hu, F. Margadant, C. Ballestrem, A. Bershadsky, G. Griffiths and H. Yu, "Kinectin-Mediated Endoplasmic Reticulum Dynamics Supports Focal Adhesion Growth in the Cellular Lamella," Journal of Cell Science, 123[22] (2010) 3901-3912

  43. E. L. C. Ng, Y. Yokomizo, N. Yamashita, B. Cirovic, H. Jin, Z. Wen, Y. Ito and M. Osato, "A Runx1 Intronic Enhancer Marks Hemogenic Endothelial Cells and Hematopoietic Stem Cells," Stem Cells, 28[10] (2010) 1869-1881

  44. S. Zhang, W. H. Tong, B. Zheng, T. A. K. Susanto, L. Xia, C. Zhang, A. Ananthanarayanan, X. Tuo, R. B. Sakban, R. R. Jia, C. Iliescu, K. H. Chai, M. McMillian, S. Shen, H. L. Leo and H. Yu, "A Robust High-Throughput Sandwich Cell-Based Drug Screening Platform," Biomaterials, 32[4] (2010) 1229-1241

  45. A. M. Raja, S. Xu, W. Sun, J. Zhou, D. C. S. Tai, C. S. Chen, J. C. Rajapakse, P. T. C. So and H. Yu, "Pulse-Modulated Second Harmonic Imaging Microscope Imaging Quantitatively Demostrates Marked Increase of Collagen in Tumor After Chemotherapy," Journal of Biomedical Optics, 15[5] (2010) 056016

  46. Y. Wei, J. Yang, A. W. H. Lin and J. Y. Ying, "A Highly Reactive Se Precursor for the Phosphine-Free Synthesis of Metal Selenide Nanocrystals," Chemistry of Materials, 22[20] (2010) 5672-5677

  47. Y. He, C. H. Kang, S. Xu, X. Tuo, S. L. Trasti, D. C. S. Tai, A. M. Raja, Q. Peng, P. T. C. So, J. C. Rajapakse, R. Welsch and H. Yu, "Towards Surface Quantification of Liver Fibrosis Progression," Journal of Biomedical Optics, 15[5] (2010) 056007

  48. Z. Yue, F. Wen, S. Gao, M. Y. Ang, P. K. Pallathadka, L. Liu and H. Yu, "Preparation of Three-Dimensional Interconnected Macroporous Cellulosic Hydrogels for Soft Tissue Engineering," Biomaterials, 31[32] (2010) 8141-8152

  49. F. Tasnim, R. Deng, M. Hu, S. Liour, Y. Li, M. Ni, J. Y. Ying and D. Zink, "Achievements and Challenges in Bioartificial Kidney Development," Fibrogenesis and Tissue Repair, 3[14] (2010)

  50. T. M. Hsieh, C. W. B. Ng, K. Narayanan, A. C. A. Wan and J. Y. Ying, "Three-Dimensional Microstructured Tissue Scaffolds Fabricated by Two-Photon Laser Scanning Photolithography," Biomaterials, 31[30] (2010) 7648-7652

  51. S. Kumar and L. Zhuo, "Longitudinal In Vivo Imaging of Retinal Gliosis in a Diabetic Mouse Model," Experimental Eye Research, 91[4] (2010) 530-536

  52. K. Saravana, S. H. Ong and K. S. W. Tan, "Robust Contour Reconstruction of Red Blood Cells and Parasites in the Automated Identification of the Stages of Malarial Infection," Machine Vision and Application, 22[3] (2010) 461-469

  53. X. Mo, Q. Li, L. W. Y. Lui, B. Zheng, C. H. Kang, B. Nugraha, Z. Yue, R. R. Jia, H. X. Fu, D. Choudhury, T. Arooz, J. Yan, C. T. Lim, S. Shen, C. H. Tan and H. Yu, "Rapid Construction of Mechanically-Confined Multi-Cellular Structures Using Dendrimeric Intercellular Linker," Biomaterials, 31[29] (2010) 7455-7467

  54. H. Zhang, S. F.-T. Lau, B. F. Heng, P. Y. Teo, P. K. D. Thilini Alahakoon, M. Ni, F. Tasnim, J. Y. Ying and D. Zink, "Generation of Easily Accessible Human Kidney Tubules on Two-Dimensional Surfaces In Vitro," Journal of Cellular and Molecular Medicine, 15[6] (2010) 1287-1298

  55. B. C. U. Tai, A. C. A. Wan and J. Y. Ying, "Modified Polyelectrolyte Complex Fibrous Scaffold as a Matrix for 3D Cell Culture," Biomaterials, 31[23] (2010) 5927-5935

  56. G. Ho, K. Saravana, Z. Y. Ke, H. N. Chan, N. Mohamed Suhaimi, Y. L. Kng, Y. Zhang and L. Zhuo, "Imidazolium Salt (DBZIM) Reduces Gliosis in Mice Treated with Neurotoxicant 2'-CH3-MPTP," CNS Neuroscience & Therapeutics, 17[3] (2010) 148-157

  57. G. Xing, J. Jiang, J. Y. Ying and W. Ji, "Fe3O4-Ag Nanocomposites for Optical Limiting: Broad Temporal Response and Low Threshold," Optics Express, 18[6] (2010) 6183-6190

  58. A. Rebuffat, C. O. Harding, Z. Ding and B. Thony, "Comparison of Adeno-Associated Virus Pseudotype 1, 2 and 8 Vectors Administered by Intramuscular Injection in the Treatment of Murine Phenylketonuria," Human Gene Therapy, 21[4] (2010) 463-477

  59. W. Zhang, L. Tucker-Kellogg, B. C. Narmada, L. Venkatraman, S. Chang, L. Ying, N. Tan, J. K. White, R. R. Jia, S. S. Bhowmick, S. Shen, C. F. Dewey, Jr. and H. Yu, "Cell Delivery Therapeutics for Liver Regeneration," Advanced Drug Delivery Reviews, 62[7-8] (2010) 814-826

  60. M. Ni, W.H. Tong, D. Choudhury, C. Iliescu and H. Yu, "Cell Culture on MEMS Platforms: A Review," International Journal of Molecular Sciences, 10[12] (2009) 5411-5441

  61. B. T. Chen, J. S. Wei and C. Iliescu, "Sonophoretic Enhanced Microneedle Array - Improving the Efficiency of Transdermal Drug Delivery," Sensors and Actuators B: Chemical, 145[1] (2009) 54-60

  62. S. M. Ong, Z. Zhao, T. Arooz, D. Zhao, S. Zhang, T. Du, M. Wasser, D. van Noort and H. Yu, "Engineering a Scaffold-Free 3D In Vitro Tumor Model for In Vitro Drug Penetration Studies," Biomaterials, 31[6] (2009) 1180-1190

  63. M. Hu, R. Deng, K. M. Schumacher, M. Kurisawa, H. Ye, K. Purnamawati and J. Y. Ying, "Hydrodynamic Spinning of Hydrogel Fibers," Biomaterials, 31[5] (2009) 863-869

  64. W. Xiang, Z. Ke, Y. Zhang, G. H. Cheng, I. D. Irwan, K. N. Sulochana, P. Potturi, Z. Wang, H. Yang, J. Wang, L. Zhuo, R. M. Kini and R. Ge, "Isthmin is a Novel Secreted Angiogenesis Inhibitor that Inhibits Tumor Growth in Mice," Journal of Cellular and Molecular Medicine, 15[2] (2009) 359-374

  65. Y. S. Pek, A. C. A. Wan and J. Y. Ying, "The Effect of Matrix Stiffness on Mesenchymal Stem Cell Differentiation in a 3D Thixotropic Gel," Biomaterials, 31[3] (2009) 385-391

  66. B. C. U. Tai, D. Chan, S. J. Gao, A. C. A. Wan and J. Y. Ying, "The Use of a Polyelectrolyte Fibrous Scaffold to Deliver Differentiated hMSCs to the Liver," Biomaterials, 31[1] (2009) 48-57

  67. M. C. C. Lim, G. Maubach and L. Zhuo, "TGF-β1 Down-regulates Connexin 43 Expression and Gap Junction Intercellular Communication in Rat Hepatic Stellate Cells," European Journal of Cell Biology, 88[12] (2009) 719-730

  68. Y. Wei, N. R. Jana, S. Tan, and J. Y. Ying, "Surface Coating Directed Cellular Delivery of TAT-Functionalized Quantum Dots," Bioconjugate Chemistry, 20[9] (2009) 1752-1758

  69. C. Y. Zhang, Z. B. Ding, N. Mohamed Suhaimi, Y. L. Kng, Y. Zhang and L. Zhuo, "A Class of Imidazolium Salts is Anti-Oxidative and Anti-Fibrotic in Hepatic Stellate Cells," Free Radical Research, 43[10] (2009) 899-912

  70. S. Kumar, S. H. Ong, S. Ranganath and F. T. Chew, "Invariant Texture Classification for Biomedical Cell Specimens via Non-Linear Polar Map Filtering," Computer Vision and Image Understanding, 114[1] (2009) 44-53

  71. L. Xia, S. Ng, R. Han, X. Tuo, H. L. Leo and H. Yu, "Laminar-Flow Immediate-Overlay Hepatocyte Sandwich Perfusion System for Drug Hepatoxicity Testing," Biomaterials, 30[30] (2009) 5927-5936

  72. D. Tai, N. Tan, S. Y. Xu, C. H. Kang, S. M. Chia, C. L. Cheng, A. Wee, L. W. Chiang, A. M. Raja, G. F. Xiao, J. C. Rajapakse, P. So and H. Yu, "Fibro-C-Index - A Comprehensive, Morphology-based Quantification of Liver Fibrosis Using Second Harmonic Generation and Two-Photon Microscopy," Journal of Biomedical Optics, 14[4] (2009) 044013

  73. J. Muck and D. Zink, "Nuclear Organization and Dynamics of DNA Replication in Eukaryotes," Frontiers in Bioscience, 14 (2009) 5361-5371

  74. R. Magalhaes, P. R. Anil Kumar, F. Wen, X. Zhao, H. Yu and L. L. Kuleshova, "The Use of Vitrification to Preserve Primary Rat Hepatocyte Monolayer on Collagen-Coated Poly(ethylene-terephthalate) Surfaces for a Hybrid Liver Support System," Biomaterials, 30[25] (2009) 4136-4142

  75. K. Narayanan, K-J. Leck, S. Gao and A. C.A. Wan, "Three-Dimensional Reconstituted Extracellular Matrix Scaffolds for Tissue Engineering," Biomaterials, 30[26] (2009) 4309-4317

  76. J. Yang and J. Y. Ying, "Room-Temperature Synthesis of Nanocrystalline Ag2S and Its Nanocomposites with Gold," Chemical Communications, 22 (2009) 3187-3189

  77. C. Zhang, S. M. Chia, S. M. Ong, S. Zhang, Y. C. Toh, D. van Noort and H. Yu, "The Controlled Presentation of TGF-β1 to Hepatocytes in a 3D Microfludic Cell Culture System," Biomaterials, 30[23-24] (2009) 3847-3853

  78. E. Fedorova and D. Zink, "Nuclear Genome Organization: Common Themes and Individual Patterns," Current Opinion in Genetics and Development, 19[2] (2009) 166-171

  79. X. Pan, X. Shi, V. Korzh, H. Yu and T. Wohland, "Line Scan Fluorescence Correlation Spectroscopy for 3D Microfluidic Flow Velocity Measurements," Journal of Biomedical Optics, 14[2] (2009) 024049

  80. H. Zhang, F. Tasnim, J. Y. Ying and D. Zink, "The Impact of Extracellular Matrix Coatings on the Performance of Human Renal Cells Applied in Bioartificial Kidneys," Biomaterials, 30[15] (2009) 2899-2911

  81. W. E. Maalouf, Z. Liu, V. Brochard, J. P. Renard, P. Debey, N. Beaujean and D. Zink, "Trichostatin A Treatment of Cloned Mouse Embryos Improves Constitutive Heterochromatin Remodeling as Well as Developmental Potential to Term," BMC Developmental Biology, 9:11 (2009)

  82. D. Van Noort, S. M. Ong, C. Zhang, S. Zhang, T. Arooz and H. Yu, "Stem Cells in Microfluidics," Biotechnology Progress, 25[1] (2009) 52-60

  83. A. Lim and R. Kraut, "The Drosophila BEACH Family Protein, Blue Cheese, Links Lysosomal Axon Transport with Motorneuron Degeneration," Journal of Neuroscience, 29[4] (2009) 951-963

  84. G. Ho, S. Kumar, X. S. Min, Y. L. Kng, M. Y. Loh, S. J. Gao, and L. Zhuo, "Molecular Imaging of Retinal Gliosis in Transgenic Mice Induced by Kainic Acid Neurotoxicity," Investigative Opthalmology and Visual Science, 50[5] (2009) 2459-2464

  85. J. Zhou, C. Bi, J. Janakaumara, S. C. Liu, W. J. Chng, K. G. Tay, L. F. Poon, Z. Xie, P. Senthilnathan, H. Yu, K. B. Glaser, D. Albert, S. Davidsen and C. S. Chen, "Enhanced Activation of STAT Pathways and Overexpression of Survivin Confer Resistance to FLT3 Inhibitors and Could Be Therapeutic Targets in AML," Blood, 113[17] (2009) 4052-4062

  86. P. Liu, Y. W. Zhang, H. Yu, X. Zhang, Q. H. Cheng, C. Lu and W. Bonfield, "Spreading of an Anchorage-Dependent Cell on a Selectively Ligand-Coated Substrate Mediated by Receptor-Ligand Binding," Journal of Biomedical Materials Research Part A, 91A[3] (2008) 806-813

  87. A. C. A. Wan, B. C. U. Tai, K. M. Schumacher, A. Schumacher, S. Y. Chin and J. Y. Ying, "Polyelectrolyte Complex Membranes for Specific Cell Adhesion," Langmuir, 24[6] (2008) 2611-2617

  88. Y. C. Toh, J. Zhang, Y. M. Khong, Y. Du, W. Sun and H. Yu, "Integrating Sensitive Quantification of Hepatic Metabolic Functions by Capillary Electrophoresis with Laser-Induced Fluorescence Detection," The Analyst, 133[3] (2008) 326-330

  89. D.-K. Chang, S.-F. Cheng, E. A. B. Kantchev, Y.-T. Liu and C.-H. Lin, "Membrane Interaction and Structure of the Transmembrane Domain of Influenza Hemagglutinin and its Fusion Peptide Complex," BMC Biology, 6[2] (2008)

  90. C. K. Sim and D. B. Forger, "Modeling the Electrophysiology of Suprachiasmatic Nucleus Neurons," Journal of Biological Rhythms, 22[5] (2007) 445-453

  91. Y. Du, R. Han, F. Wen, S. Ng, L. Xia, T. Wohland, H. L. Leo and H. Yu, "Synthetic Sandwich Culture of 3D Hepatocyte Monolayer," Biomaterials, 29[3] (2007) 290-301

  92. S. M. Ong, L. He, N. T. T. Linh, Y. H. Tee, T. Arooz, G. P. Tang, C. H. Tan and H. Yu, "Transient Inter-Cellular Polymeric Linker," Biomaterials, 28[25] (2007) 3656-3667

  93. Y. Du, R. B. Han, S. Ng, J. Ni, W. X. Sun, T. Wohland, S. H. Ong, L. Kuleshova and H. Yu, "Identification and Characterization of a Novel Pre-Spheroid 3D Hepatocyte Monolayer on Galactosylated Substratum," Tissue Engineering, 13[7] (2007) 1455-1468

  94. S. M. Liu, L. Liu, Z. P. Xu, A. Yu, G. Q. Lu and J. C. D. da Costa, "Bioceramic Macrocapsules for Cell Immunoisolation," Angewandte Chemie International Edition, 46[17] (2007) 3062-3065

  95. G. Maubach, M. C. C. Lim, S. Kumar and L. Zhuo, "Expression and Upregulation of Cathepsin S and Other Early Molecules Required for Antigen Presentation in Activated Hepatic Stellate Cells upon IFN-γ Treatment," Biochimica et Biophysica Acta - Molecular Cell Research, 1773[2] (2006) 219-231

  96. C. Y. Zhang and L. Zhuo, "EGCG and Genistein Attenuate GFAP Elevation Induced by Fibrogenic Cytokines in Hepatic Stellate Cells," International Journal of Molecular Medicine, 18[6] (2006) 1141-1151

  97. X. T. Pan, Y. C. Toh, H. Yu and T. Wohland, "Characterization of Poly(acrylic acid) Diffusion Dynamics on the Grafted Surface of Poly(ethylene Terephthalate) Films by Fluorescence Correlation Spectroscopy," Biophysical Review and Letters, 1[4] (2006) 433-441

  98. L. L. Ong, P. C. Lin, X. Zhang, S. M. Chia and H. Yu, "Kinectin-Dependent Assembly of Translation Elongation Factor-1 Complex on Endoplasmic Reticulum Regulates Protein Synthesis," Journal of Biological Chemistry, 281[44] (2006) 33621-33634

  99. E. K. F. Yim, A. C. A. Wan, C. Le Visage, I. C. Liao and K. W. Leong, "Proliferation and Differentiation of Human Mesenchymal Stem Cell in Polyelectrolyte Complexation Fibrous Scaffold," Biomaterials, 27[36] (2006) 6111-6122

  100. F. Wen, S. Chang, Y. C. Toh, S. H. Teoh and H. Yu, "Development of Poly (Lactic-co-glycolic Acid)-collagen Scaffolds for Tissue Engineering," Materials Science and Engineering: C, 27[2] (2006) 285-292

  101. A. C. A. Wan, B. C. U. Tai, K.-J. Leck and J. Y. Ying, "Silica-Incorporated Polyelectrolyte Complex Fibers as Tissue Engineering Scaffolds," Advanced Materials, 18[5] (2006) 641-644

  102. G. Maubach, M. C. C. Lim, C. Y. Zhang and L. Zhuo, "Glial Fibrillary Acidic Protein Promoter Directs lacZ Expression Specifically in a Rat Hepatic Stellate Cell Line," World Journal of Gastroenterology, 12[5] (2006) 723-730

  103. S. C. Wong, H. Yu and J. B. So, "Detection of Telomerase Activity in Gastric Lavage Fluid: A Novel Method to Detect Gastric Cancer," Journal of Surgical Research, 131[2] (2006) 252-255

  104. H. F. Lu, W. S. Lim, P. C. Zhang, S. M. Chia, H. Yu, H.-Q. Mao and K. W. Leong, "Galactosylated PVDF Hollow Fiber Bioreactor for Hepatocyte Culture," Tissue Engineering, 11[11-12] (2006) 1667-1677

  105. I. C. Liao, A. C. A. Wan, E. K. F. Yim and K. W. Leong, "Controlled Release from Fibers of Polyelectrolyte Complexes," Journal of Controlled Release, 104[2] (2005) 347-358

  106. Y. C. Toh, S. Ng, Y. M. Khong, V. Samper and H. Yu, "A Configurable 3D Microenvironment in a Micro-Fluidic Channel for Primary Hepatocytes Culture Assay and Drug Development," Technologies, 3[2] (2005) 169-176

  107. C. W. Tan and Y. Y. Yang, "pH-Triggered Thermally Responsive Polymer Core-Shell Nanoparticles for Targeted Drug Delivery," Advanced Materials, 17[3] (2005) 318-323

  108. Y. C. Toh, S. T. Ho, Y. Zhou, D. W. Hutmacher and H. Yu, "Application of Polyelectrolyte Complex Coacervation to Improve the Seeding Efficiency of Bone Marrow Stromal Cells in 3D Scaffolds," Biomaterials, 26[19] (2004) 4149-4160

Research Staff

YING Jackie Yi-Ru, Executive Director

YU Hanry, Group Leader

WAN Chwee Aun Andrew, Team Leader and Principal Research Scientist

ZINK Daniele, Team Leader and Principal Research Scientist
SPOTLIGHT

The Use of a Library of Industrial Materials to Determine the Nature of Substrate-Dependent Performance of Primary Adherent Human Cells
Biomaterials, (2011)
DOI:10.1016/j.biomaterials.2011.09.063

From Short Peptides to Nanofibers to Macromolecular Assemblies in Biomedicine
Biotechnology Advances, (2011)
DOI:10.1016/j.biotechadv.2011.10.004.

The Production of 5-Hydroxymethylfurfural from Fructose in Isopropyl Alcohol: A Green and Efficient System
ChemSusChem, (2011)
DOI:10.1002/cssc.201100489

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14 Feb
IBN Seminar Series: Cellular and Molecular Regulation of Branching Morphogenesis in the Human Breast: A 3D Culture Approach by Prof. Prof. Thorarinn Gudjonsson, University of Iceland, Iceland

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