PhD (National University of Singapore)
PhD (National University of Singapore)
Broad area of research: Infrastructure
Main research areas
Professor Hutmacher’s background is a strong combination of academic and industrial. His expertise is in biomaterials, biomechanics, medical devices and tissue engineering. He is one of the few academics to take a holistic bone engineering concept to clinical application. More than 400 patients have been treated with the FDA-approved bone engineering scaffolds developed by Prof Hutmacher’s Singapore-based interdisciplinary research group.
Over the last 4 years, Professor Hutmacher has developed an international track record in adult stem cell research related to regenerative medicine.
Regenerative medicine/tissue engineering is a rapidly growing multidisciplinary field involving the life, physical and engineering sciences and seeks to develop functional cell, tissue and organ substitutes to repair, replace or enhance biological function that has been lost due to congenital abnormalities, injury, disease or aging. It includes both the regeneration of tissues in vitro for subsequent implantation in vivo as well as regeneration directly in vivo. In addition to having a therapeutic application, tissue engineering can have a diagnostic application where the engineered tissue is used as a biosensor. Engineered tissues can also be used for the development of drugs including screening for novel drug candidates, identifying novel genes as drug targets, and testing for drug metabolism, uptake, and toxicity.
Professor Hutmacher has three main areas of research:
- Bone Graft
- 3D Cell Cultures
Research area 1: Cartilage
Large cartilage defects are a significant cause of pain, immobility and decreased quality life for people world-wide. Clinical cartilage tissue engineering approaches are restricted to younger patients (<50) and defects smaller than 10 cm^2. We hypothesize that zonal cartilage characteristics are important for overcoming these current limitations. We aim to study the molecular characteristics of zonal chondrocytes under dynamic cell culture conditions and to differentiate mesenchymal stem cells into lubricant-producing chondrocytes. This work leads to the development of a novel cartilage engineering technology platform to deliver structural and functional zonal properties, and allow for treatment of older patients and larger defects.
Research area 2: Bone Graft
Bone grafts are frequently used to treat conditions in load-bearing regions of the body. In the present climate of increasing life expectancy with an ensuing increase in bone-related injuries, orthopaedic surgery is undergoing a paradigm shift from bone grafting to bone engineering, where a scaffold is implanted to provide adequate load bearing and enhance tissue regeneration. However, scaffolds in combination with internal or external fixation are in many cases not sufficient to regenerate a critical sized bone defect. Analysis of tissue engineering literature indicates that future generations of engineered scaffolds will not be successful by simply integrating drug delivery systems within the scaffolds. Instead, using knowledge of drug delivery and biomaterial science, multifunctional scaffolds, where the three-dimensional (3D) template itself acts as a biomimetic, programmable and multi-drug delivery device should be designed.
To our knowledge no multiple-growth-factor (GF)-releasing scaffold systems of high porosity (> 80%) are currently clinically available for the treatment of medium to high load-bearing bone defects. To address this therapeutic challenge we aim to marry two leading-edge scaffold technologies; biomechanically loadable composite scaffolds (produced by computer aided design and rapid prototyping) and microparticle delivery systems, incorporating important bone regeneration-related GFs which possess controllable release kinetics (Figure 1). We will combine a well established scaffold-technology platform developed by Professor Dietmar Hutmacher’s group at QUT, with the innovative controlled-release technology developed by Shakesheff’s group at Nottingham University to provide a leading edge solution to this therapeutic challenge. We will characterise and test these novel engineered bone graft systems (EBGS) both in vitro and in vivo.
We hypothesise that a composite scaffold (already successfully utilised in low-load bearing bone defects) can be biomechanically optimised and be combined with controlled delivery of angiogenic (PDGF/VEGF) and osteoinductive (BMP) molecules producing a biologically active EBGSs with mechanical properties suitable for load-bearing applications.
Research area 3: 3D Cell Cultures
Biomedical researchers have become increasingly aware of the limitations of conventional 2D tissue cell cultures where most tissue cell studies have been carried out. They are now searching for 3D cell culture systems, something between a petri dish and a mouse. It has become apparent that 3D cell culture offers a more realistic micro- and local-environment where the functional properties of cells can be observed and manipulated that is not possible in animal experiments.
Nearly all tissue cells are embedded in 3-dimension (3D) microenvironment in the body. On the other hand, nearly all tissue cells including most cancer and tumor cells have been studied in 2-dimension (2D) petri dish, 2D multi-well plates or 2D glass slides coated with various substrata. The architecture of the in situ environment of a cell in a living organism is 3D, cells are surrounded by other cells, where many extracellular ligands including many types of collagens, laminin, and other matrix proteins, not only allow attachments between cells and the basal membrane but also allow access to oxygen, hormones, and nutrients; removal of waste products and other cell types associated in tissues. The in vivo environment of cells consists of a complex 3D network of extra-cellular matrix nano to micro fibers with micro to nanopores that create various local microenvironments.
Hence, there are several key drawbacks to 2D cell cultures. First, the movements of cells in the 3D environment of a whole organism typically follow a chemical signal or molecular gradient. Molecular gradients play a vital role in biological differentiation, determination of cell fate, organ development, signal transduction, neural information transmission and countless other biological processes. However, it is nearly impossible to establish a true 3D gradient in 2D culture.
Second, cells isolated directly from higher organisms frequently alter metabolism and alter their gene expression patterns when in 2D culture. It is clear that cellular structure plays a major role in determining cellular activity, though spatial and temporal extracellular matrix protein and cell receptor interactions that naturally exist in tissues and organs. The cellular membrane structure, the extracellular matrix and basement membrane significantly influences cellular metabolism, via the protein–protein interactions. The adaptation of cells to a 2D petri dish requires significant adjustment of the surviving cell population not only to changes in oxygen, nutrients and extracellular matrix interactions, but also to alter waste disposal.
Third, cells growing in a 2D environment can significantly alter production of their own extracellular matrix proteins and often undergo morphological changes. It is not unlikely that the receptors on cell surface could preferentially cluster on parts of the cell that directly expose to culture media rich in nutrients, growth factors and other extracellular ligands; whereas, the receptors on the cells attached to the surface may have less opportunity for clustering. Thus, the receptors might not be presented in correct orientation and clustering, this would presumably also affect communication between cells.
The development of new 3D culture systems, particularly those biologically inspired nanoscale scaffolds and/or hydrogels mimicking in vivo environment that serve as permissive substrates for cell growth, differentiation and biological function is a most actively pursuit area of the Hutmacher lab. These novel 3D culture systems will be useful not only for further our understanding of cell biology in a more physiological in vitro environment, but also for advancing cancer research, tissue engineering & regenerative medicine.
EP 701417A1: Anastomosis Device | WO 9732616A1: Covering membrane, Molded Bodies Produced There from and Process for the Production Thereof | WO 9734546A1: Producing a Bone Substitute Material | WO 9726028A2: Fastening Nail | Filed: Design and Fabrication of PCL Scaffolds via Fused Deposition Modeling | Filed: Biaxial Continuous Flow Bioreactor | Filed: Bioresorbable Burr Plug
Professor Hutmacher has received over $US6.5M in research funding since 1991.
Selected list of awarded grants
Ongoing research support
- Start up grant from QUT for Chair over a period of 3 years AUD 250,000/year
- ARC Grant 3 years AUD 220,000/year
- Prostate Cancer Foundation 2 years AUD 200,000/year
Complete research support
- Landesministerium fuer Bildung, Wissenschaft, Forschung und Technologie Baden-Wuertemberg,’The development of a bioresorbable device for the refixation of bony fragments in orthopedic surgery’, Principle Investigator, 1991-1992, US$ 210,000
- Landesministerium fuer Bildung, Wissenschaft, Forschung und Technologie Baden-Wuertemberg,’The development of a bioresorbable screw-plate system for cranio- and maxillofacial surgery’, Principle Investigator, 1991-1992, US$ 100,000
- University of Ulm, ‘Experimental evaluation of Poly (L-lactide-co-D,L-lactide) in the ratio 97,5/2,5 ligament for anterior cruciate ligament augmentation’, Co-Investigator, 1991-1992, US$ 120,000
- Bundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, ‘Guided bone regeneration around dental implants with large circumferential osseous defects with a new bioresorbable device. An experimental study on the monkey’, Principle Investigator, 1992-1993, US$ 60,000
- Bundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, ‘Bone regeneration around endosseous oral implants using a new bioresorbable membrane ‘, Principle Investigator, 1993-1994, US$ 35,000
- Bundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, ‘Experimental Investigation of a new bioresorbable device to facilitate guided bone regeneration around dehisced implants‘, Principle Investigator, 1993-1994, US$ 28,000
- Bundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, ‘Effect of calcium hydroxide paste on the bone healing and osseointegration around titanium dental implants ‘, Principle Investigator, 1993-1994, US$ 20,000
- Landesministerium fuer Bildung, Wissenschaft, Forschung und Technologie Thueringen, ‘Development and processing of a polyurethane-glass ceramic biomaterial for artificial hip cups. Co-Investigator, 1993-1994, US$ 120,000
- Landesministerium fuer Bildung, Wissenschaft, Forschung und Technologie Thueringen, ‘Development and manufacturing of fast and slow resorbing glass ceramics’, Co-Investigator, 1993-1994, US$ 75,000
- Boehringer Ingelheim, ‘The market of bioresorbable polymers and devices in Europe -State of the Art/Future Perspectives, Principle Investigator,1995, US$ 6,000
- Bundesministerium fur Bildung, Wissenschaft, Forschung und Technologie, ‘Guided bone regeneration – The investigation of a new design concept and a processing technology for bioresorbable composite membranes ‘, Principle Investigator,1995-1999, US$ 65,000
- IMZ GmbH, ‘The development of a tissue engineered membrane for soft and hard tissue repair’, Principle Investigator,1996-1999, US$ 60,000
1999 – 2001
- National University of Singapore, Faculty of Engineering, The Design and Processing of Three-Dimensional Bioresorbable Scaffolds for Tissue Engineering a Bone/Cartilage Interphase, Co- Principle Investigator, 1999 – 2001, US$ 160,000
2000 – 2002
- National University of Singapore, Faculty of Engineering, Flow Environment and Cell Growth in Tissue Engineering, Co-Investigator, 2000 – 2002, US$ 60,000
- National University of Singapore, Faculty of Engineering, Application of Biodegradable Polymeric Microspheres for Delivery of Cell Growth Factors in Tissue Engineering of Heart Valves, Co-Investigator, 2000 – 2002, US$ 80,000
- Singapore Polytechnic, Design and Fabrication of a Bioreactor for Tissue Engineering Applications, Co-PI Investigator, 2000 – 2002, US$ 125,000
- Singapore General Hospital, Reconstruction of Craniofacial Defects with Tissue Engineered Bone Transplants – An Animal Study in Yorkshire Pigs, Collaborator, 2000 – 2001, US$ 18,000
- National University of Singapore, Faculty of Dentistry, Tissue Engineering of a Autogenous Transplant Around Dental Implants in the Atrophic Alveolar Ridge Using a Bioresorbable 3D Scaffold, Osteoblasts and Bone Growth Factors, Collaborator, 2000 – 2002, US$ 120,000
- ITI Foundation, Waldenburg Switzerland, The augmentation of Atrophied Mandibles via Tissue Engineered Bone – A Clinical Study, Collaborator, 2000 – 2002, US$ 20,000
- National University of Singapore, Faculty of Medicine. The Efficacy of BMP-7 and TGF-beta1 in transforming Mesenchymal Stem Cells into bone in a biodegradable polymer scaffold- an in vitro study. Collaborator, 2000 – 2002, US$ 65,000
2000 – 2003
- National University of Singapore, Faculty of Medicine, The Application of a Bioresorbable 3D Scaffold, Mesenchymal Stem Cells and Bone Growth Factors for Tissue Engineering a Articular Bone/Cartilage Interphase, Collaborator, 2000 – 2003, US$ 120,000
- National University of Singapore, Faculty of Engineering, Robotic Micro-assembly Fabrication of Three-dimensional Bioresorbable Scaffolds for Tissue Engineering, Co- Principle Investigator, 2000 – 2003, US$ 100,000
- National University of Singapore, Faculty of Engineering, Development of A Desk-Top Rapid Prototyping (RP) System for Tissue Engineering, Co- Investigator, 2000 – 2002, US$ 35,000
- National University of Singapore, Faculty of Engineering, Relationship between material stiffness and cell adaptation in tissue engineered scaffolds, Collaborator, 2001 – 2003, US$ 100,000
- National University of Singapore, Faculty of Medicine. The Experimental Evaluation of a Tissue Engineered Bone Graft for Cranial Reconstruction, Co- Principle Investigator, 2001 – 2003, US$ 120,000
- National University of Singapore, Faculty of Dentistry, Tissue Engineering of an Autogenous Periodontal Transplant for the Regeneration of the Periodontium, Co- Investigator – 2003, US$ 110,000
- National University of Singapore, Office of Life Sciences, NUS/OLS Young Investigator Award Tissue Engineering Bone and Cartilage- Characterization and Large Scale Culturing of Human Bone Marrow Derived Mesencymal Stem Cells in Novel Scaffold Architectures, Principle Investigator, 2002-2004, US$ 350,000
- Singapore Biomedical Research Council, The Study of Tissue Engineered Osteochondral and Cranial Bone Grafts in an Goat Model, Principle Investigator, 2002-2004, US$ 450,000
- Singapore Defence Medical Research Institute, Tissue Engineering of a Skin Graft, Principle Investigator, 2003-2004, US$ 40,000
- National Medical Research Council, Singapore, Role of OP1 in enhancing anterior lumbar interbody fusion allografts, 2003-2004, Co-Investigator US $ 150,000
- NUS Tissue Engineering Program “A Proposed Flagship Research Program at the National University of Singapore” , Co-Investigator U$ 1.5 Mill. 2004-2005
- Singapore Biomedical Research Council, Spine Tissue Engineering, Co-Investigator, 2003-2006, US$ 450,000
- Singapore Biomedical Research Council, Mesenchymal Stem Cell Tissue Engineering, Co-Investigator, 2003-2006, US$ 1 Mill
- Singapore Biomedical Research Council, Development of Autologous Corporal Tissue For Male Erectile Dysfunction, Co-Investigator, 2003-2006, US$ 400,000
- National Medical Research Council, Singapore, Tissue engineered prefabricated vascularised bone flaps., 2004-2005, Co-Investigator US$ 70,000
- NIH, Runx2 expression on gene/protein expression and matrix mineralization by cells cultured in 3-D polymeric scaffolds, Collaborator, 2003-2008, US$ 350,000
- AO Research Fund, Switzerland, Development of a Tissue engineered bone substitute for bridging large, weight bearing, cortical defects. An experimental study in the adult sheep, Co-Investigator, 2004-2005 US$ 70,000
- Singapore Biomedical Research Council, Bone tissue engineering by using novel scaffold systems doped with heparan sulphate. Principle Investigator, 2005-2007, US$ 350,000
- 2006 – 2009 A Composite Material Technology Platform For Bone Engineering Principle Investigator, 2007-2007, US$ 500,000
Awards and recognitions
Over the last 9 years Professor Hutmacher has gained a worldwide reputation in the field of tissue engineering/regenerative medicine. He received the inaugural National University of Singapore Young Investigator Award in 2002, which included a grant of $550 000. Professor Hutmacher and his students have received numerous research awards including the Innovation Award of the German Industry and Commerce Association, Award for Best Table Clinic of the Twelfth Annual Meeting of the Academy of Osseointegration, and Young Investigator Award of the 10th International Conference on Biomedical Engineering.
In 2003 his research team was awarded the Best Article published in the International Journal of Oral Maxillofacial Implants for the 2002 article “Evaluation of a Tissue Engineered Membrane-Cell Construct for Guided Bone Regeneration”.
He received a gold award in the Asian Innovation Awards in 2004, and was featured in the Far East Economic Review, a publication in the Wall Street Journal Group; in that year his research team also received the IES Prestigious Engineering Achievement Award for the conference paper Platform Technology in Tissue Engineered Scaffolds: Integration of Medical Imaging, Biomaterials and Advanced Manufacturing.
He has received 7 best conference paper awards including:
- 1st prize (oral presentation) at the 6th Annual International Conference and Exposition of the Tissue Engineering Society International, Orlando, USA, 2003
- Winner of the Resident’s Research presentation at the Singapore Society of Otolarynology Annual meeting, Singapore, 2004
- Winner of “The Mimics Innovation Award” in category 1: Innovative implant design system. Annual Conference of “Computer Guided Implantology & 3D Medical Modelling”, Leuven, Belgium, 2005. (€5000).
In 2020, Professor Hutmacher was also recognised as a ‘Lifetime Achiever’, being listed among the top 40 Australian researchers and the top 5 Australian researchers in the fields of Engineering and Computer Sciences. He was also ranked among the top 2% of scientists in the world from Scopus’ citation metrics database.
2008 – Present Adjunct Professor at Georgia Tech | 2007 – Present Professor and Chair Regenerative Medicine, Institute of Biomedical Innovation, QUT | 2005 – 2007 Joint Appointment as Associate Professor (Tenure), Division of Bioengineering, Department of Orthopedic Surgery, National University of Singapore | 2001 – 2005 Joint Appointment as Assistant Professor, Division of Bioengineering, Department of Orthopedic Surgery, National University of Singapore | 1999 – 2001 Senior Research Fellow, National University of Singapore | 1998 – 1999 Managing Director, Medical Monitor gmbh | 1995 – 1998 Assistant Professor (part time), Department of Mechanical Engineering, University for Applied Science. Offenburg, Germany | 1995 – 1999 Hutmacher Implant Innovation (Self-Employed) | 1993 – 1994 Managing Director, BIOVISION gmbh | 1990 – 1994 Senior Lecturer (part time), Dept of Mechanical Engineering, University for Applied Science. Offenburg, Germany | 1989 – 1992 Senior Lecturer (part time), Dept of Mechanical Engineering, University for Applied Science. Offenburg, Germany | 1989 – 1992 Head of R&D Department, Biomaterials, G. Hug Gmbh | 1989 – 1989 R&D Engineer, Boehringer Mannheim