NUS Tissue Engineering Programme

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Research Theme

 

The NUS Tissue Engineering Programme (NUSTEP) is a multidisciplinary programme that aims to develop core competencies and to create innovations in cell and construct technologies for effective integration of living systems for clinical therapies. The goal is to establish a globally competitive programme in tissue engineering with significant research outcomes that will result in international recognition for high quality research with clinical and industrial applications.

  • To engage basic scientists and clinicians in the strategic development of translational research in Tissue Engineering
  • To develop strong partnerships with research institutes, both locally and abroad to develop a world-class program in Tissue Engineering
  • To create a conducive environment for education and training of research manpower
  • To develop industrial outreach programs in the field of Tissue Engineering
  • To raise the global profile of the Programme by participating in International Conferences
  • To establish cGTP shared core facilities in NUHS for translational research infrastructure

 

Programme Activities                      

 

Strategic technologies particularly for tissues regeneration crucial to musculoskeletal tissue engineering and regenerative medicine, such as bone, cartilage, tendon, ligament and skin, as well as the development of suitable collagen matrices to support tissue regeneration. In order to fully utilize the therapeutic potential of stem cells, it is important to understand the intrinsic property of stem cells and the role of the microenvironment in modulating stem cell behavior and function. Microenvironmental factors such as mechanical cues, bioactive factors and matrix /scaffold properties not only regulate stem cell differentiation, but also modulate stem cell signaling to the surrounding environment. Successful tissue engineering using stem cells will require the clever manipulation of a combination of these factors.

Tissue engineering approaches with a combination of cells, biofactors and scaffolds. Patients derived stem cells, expanded ex vivo, are subsequently mixed with morphogens and placed in a 3D scaffold to initiate differentiation. The engineered scaffold will either undergo a period of ex vivo pre-implantation differentiation culture or directly implanted in vivo for tissue regeneration.

 

The programme focuses on the following major areas:

 

  1. Biomimetic Scaffold Technologies: Design and develop novel biocompatible and biofunctional constructs for tissue engineering applications. Biofunctionalisation includes the use of regulatory biomolecules and control delivery systems.
  2. Stem Cell Science: Discovery of new knowledge and greater understanding of adult and embryonic stem cells in regenerative medicine applications and the development of cell therapies for repair and regeneration of skeletal tissues.
  3. Tissue Modulation: Modulate the composition and stability of tissue by manipulating intrinsic or exogenous extracellular matrix (ECM).
  4. Musculoskeletal tissue engineering and regeneration: Validate our in vitro approaches using porcine model.
  5. Clinical trial for cell-based therapy: Translate the research bench work to clinical application

 

Programme Highlights

 

With the help of Division of Bioengineering in NUS, our research programme has:

  • Developed a rapid prototyping system for the fabrication of tissue engineering scaffolds with complex geometries.
  • Developed a novel material compositions based on a composite of biodegradable polymers ceramics specifically aimed for bone tissue regeneration.
  • Fabricated a combined silk scaffold with microporous sponges for ligament tissue engineering application.
  • Identified novel factors and biomaterial which enhance the development of cartilage with superior quality, in collaboration with Genome institute of Singapore.

 

Currently, we are also:

  • Conducting an observational clinical study designed to compare the effectiveness of chondrocytes and mesenchymal stem cells as sources of cells for ACI, at cGTP facilities in NUHS.
  • Rolling out a unique application platform for the use of Macromolecular Crowding, a biophysical principle that create in vivo-like environments for the benefit of cell culture systems.

 

Research Achievements

 

Grants won in FY2008

Project title

PI

Project Value (Grantor)

Modelling growth plate function with bone marrow derived mesenchymal stem cells to develop improved treatments for growth plate defects in children

Lee Eng Hin

$871,000 (NMRC)

Translational study of autologous bone marrow stem cell in TGF-beta 1 loaded fumarate based hydrogel for chondral defect repairing

James Hui

$475,188 (NMRC)

Tri-phasic silk/stem cell based bone ligament bone construct in the repair of medial collateral ligament in rabbits

James Goh

$185,000 (NMRC)

Control release of recombinant human bone morphogenetic protein type 2 from heparin conjugated multilayered alginate microbeads to enhance new bone formation in spine fusion

Wong Hee Kit & James Goh

$170,000 (NMRC)

Development and characterization of xeno-/serum-free medium for the enhancement of human bone marrow mesenchymal stem cells ex vivo expansion suitable for efficient clinical cellular therapy

Yang Zheng

$171,000 (NMRC)

CNP-modified alginate for cell-based cartilage tissue engineering

Guo Ximin

$199,706 (NMRC)

Imaging of transplanted bone marrow derived stem cells (BMSCs) by MRI in chondral defect, meniscus injury and diabetic neuropath

James Hui

$590,908 (SBIC)

 

Patents

 

  1. 96-well perfusion bioreactor for in vitro drug screening.
    SG Patent Application No.: 200902107-2, Filed: 26/03/2009
  2. Bioactive Surface for hepatocyte-based applications.
    US Patent Application No.: 12/301,890, Exploit Tech Ref: IBN/P/04260/09/US.
    EU Patent Application No.: 07748592.6 - 1222, Filed: 14/01/09
    Exploit Technologies Ref: IBN/P/04260/07/JP, Filed: 20 /11/2008.
  3. Forming Porous Scaffold from Cellulose Derivatives
    Exploit Tech Ref: IBN/P/04870/01/PCT, International Application No.: PCT/SG2008/000.
  4. Forming cell structure with transient linker in cage.
    Exploit Techs Ref: IBN/P/04803/01/PCT.
  5. High throughput cell based assays fabricated with integrated silicon and cell culture technologies.
    SG Patent Application No.: 200804836-5, Exploit Tech Ref: IBN/P/04022/07/SG, Filed: 26/06/2008.
  6. Linear & Logarithmic Gradient Generator.
    Patent Application No.: IBN/P/05016/01/US.
  7. Bioactive Scaffold with Controllable Mass Transfer Properties Independent of Mechanical Strength.
    Filed: 25/06/2008. Patent Application No.: 61/129,424, Exploit Tech Ref: IBN/P/05081/00/US. 
  8. Cell Culture Device.
    US Patent Application No. 11/667,715, Exploit Tech Ref: IBN/P/02205/05/US, Filed: 07/01/2008.
  9. Microfluidic delivery of reagents and samples
    US Provisional Patent Application: IBN/P/05050/00/US, Filed:10/07/2008

 

Spin-off Companies

 

Dr Phan Toan Thang: CellResearch Corp Pte  Ltd (2002) CardLab Pte Ltd (2005),

                                         Advanced Biological Surgery Pte Ltd (2005), MekoStem Ltd (2007)

Prof Teoh Swee Hin:   Osteopore International (2003)

 

Key Representative Publications

 

  1. Fan H, Liu H, Wong EJ, Toh SL, Goh JC. In vivo study of anterior cruciate ligament regeneration using mesenchymal stem cells and silk scaffold. Biomaterials 29(23):3324-37. (2008)
  2. Abbah SA, Lam CX, Hutmacher DW, Goh JC, Wong HK. Biological performance of a polycaprolactone-based scaffold used as fusion cage device in a large animal model of spinal reconstructive surgery. Biomaterials 30(28):5086-93. (2009)
  3. Lee KB, Hui JH, Song IC, Ardany L, Lee EH. Injectable mesenchymal stem cell therapy for large cartilage defects--a porcine model. Stem Cells. 25(11):2964-71. (2007)
  4. Liu H, Fan H, Wang Y, Toh SL, Goh J. The interaction between a combined knitted silk scaffold and microporous silk sponge with human mesenchymal stem cells for ligament tissue engineering. Biomaterials 29(6):662-674. (2008)
  5. Harve KS, Vigneshwar R, Rajagopalan R, Raghunath M. Macromolecular crowding in vitro as means of emulating cellular interiors: When less might be more. Proceedings of the National Academy of Sciences of the United States of America. 105(51):E119. (2008)
  6. Sawyer, A. A.; Song, S. J.; Susanto, E.; Chuan, P.; Lam, C. X. F.; Woodruff, M. A.; Hutmacher, D. W.; Cool, S. M., The stimulation of healing within a rat calvarial defect by mPCL-TCP/collagen scaffolds loaded with rhBMP-2. Biomaterials 30 (13):2479-2488. (2009)
  7. Zhang, H.; Burdet, E.; Poo, A. N.; Hutmacher, D. W., Microassembly fabrication of tissue engineering scaffolds with customized design. IEEE Transactions on Automation Science and Engineering 5 (3):446-456. (2008)
  8. Wu YN, Yang Z, Hui JH, Ouyang HW, Lee EH. Cartilaginous ECM component-modification of the micro-bead culture system for chondrogenic differentiation of mesenchymal stem cells. Biomaterials. 28(28):4056-67. (2007)
  9. Rider, D. A.; Dombrowski, C.; Sawyer, A. A.; Ng, G. H. B.; Leong, D.; Hutmacher, D. W.; Nurcombe, V.; Cool, S. M., Autocrine fibroblast growth factor 2 increases the multipotentiality of human adipose-derived mesenchymal stem cells. Stem Cells 26 (6):1598-1608. (2008)
  10. Liu TM, Martina M, Hutmacher DW, Hui JH, Lee EH, Lim B. Identification of common pathways mediating differentiation of bone marrow- and adipose tissue-derived human mesenchymal stem cells into three mesenchymal lineages. Stem Cells 25(3):750-60. (2007)

 

Member(s) of Programme

 

Programme director:

Prof James Goh Cho Hong

 

Members:

Prof Lee Eng Hin

Prof Casey Chan

Prof Wong Hee Kit

Assoc Prof James Hui Hoi Po

Assoc Prof Michael Raghunath

Prof Teoh Swee Hin

Assoc Prof Toh Siew Lok

Asst Prof Phan Toan Thang

Research Staff:

Dr Yang Zheng

Dr Jacqueline Frida Schmitt

Dr Liu Tongming

Dr Guo Ximin

Dr Abbah Sunny Akogwu

Dr. Sambit Sahoo

Dr. Harve Karthik

 

 

Contact Details

 

Mr Eriza Amranto, Executive

NUS Tissue Engineering Programme

Life Science Institute,

DSO (Kent Ridge) Building,

National University of Singapore

27 Medical Drive #04-01,

Singapore 117510

Tel      :     6516 5301

Fax      :     6776 5322

Email  :     lsiea@nus.edu.sg