Distinguished Professor
Dietmar W Hutmacher

Biography

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:

• Cartilage
• 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. Patents

EP 701417A1: Anastomosis DeviceWO 9732616A1: Covering membrane, Molded Bodies Produced There from and Process for the Production ThereofWO 9734546A1: Producing a Bone Substitute MaterialWO 9726028A2: Fastening Nail Filed: Design and Fabrication of PCL Scaffolds via Fused Deposition ModelingFiled: Biaxial Continuous Flow BioreactorFiled: Bioresorbable Burr Plug Grants 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

1991-1992

1. 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
2. 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
3. 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

1992-1993 

1. 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

1993-1994

1. 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
2. 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
3. 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
4. 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
5. 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

1995-1999

1. Boehringer       Ingelheim, ‘The market of bioresorbable polymers  and devices in Europe       -State of the Art/Future Perspectives,  Principle Investigator,1995, US$       6,000
2. 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
3. IMZ       GmbH, ‘The development of a tissue engineered membrane  for soft and hard       tissue repair’, Principle  Investigator,1996-1999, US$ 60,000

1999 – 2001

1. 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

1. National University       of Singapore,       Faculty of  Engineering, Flow Environment and Cell Growth in Tissue        Engineering, Co-Investigator, 2000 – 2002, US$ 60,000
2. 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
3. Singapore       Polytechnic, Design and Fabrication of a  Bioreactor for Tissue Engineering       Applications, Co-PI  Investigator, 2000 – 2002, US$ 125,000
4. Singapore General       Hospital, Reconstruction of        Craniofacial Defects with Tissue Engineered Bone Transplants - An Animal        Study in Yorkshire Pigs, Collaborator,       2000 – 2001, US$  18,000
5. 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
6. ITI       Foundation, Waldenburg Switzerland, The augmentation of  Atrophied       Mandibles via Tissue Engineered Bone – A Clinical  Study, Collaborator,       2000 – 2002, US$ 20,000
7. 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

1. 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
2. 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
3. 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
4. National University       of Singapore,       Faculty of  Engineering, Relationship between material stiffness and cell        adaptation in tissue engineered scaffolds, Collaborator, 2001 – 2003,  US$       100,000
5. 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
6. 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

2002-2004

1. 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
2. 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

2003-2004

1. Singapore       Defence Medical Research Institute, Tissue  Engineering of a Skin Graft,       Principle Investigator, 2003-2004,  US$ 40,000
2. National       Medical Research Council, Singapore, Role of OP1  in enhancing anterior       lumbar interbody fusion allografts,  2003-2004, Co-Investigator US $       150,000
3. NUS       Tissue Engineering Program “A Proposed Flagship  Research Program at the National University       of Singapore”       ,  Co-Investigator U$ 1.5 Mill. 2004-2005

2003-2006

1. Singapore       Biomedical Research Council, Spine Tissue  Engineering, Co-Investigator,       2003-2006, US$ 450,000

1. Singapore       Biomedical Research Council, Mesenchymal Stem  Cell Tissue Engineering,       Co-Investigator, 2003-2006, US$ 1 Mill
2. Singapore       Biomedical Research Council, Development of  Autologous Corporal Tissue For       Male Erectile Dysfunction,  Co-Investigator, 2003-2006, US$ 400,000
3. National       Medical Research Council,        Singapore,        Tissue engineered prefabricated       vascularised bone flaps.,  2004-2005, Co-Investigator US$ 70,000

2003-2008

1. NIH,       Runx2 expression on gene/protein expression and matrix  mineralization by       cells cultured in 3-D polymeric scaffolds,  Collaborator, 2003-2008, US$       350,000
2. 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

2005-2007

1. Singapore Biomedical       Research Council, Bone tissu e  engineering by using novel scaffold       systems doped with heparan  sulphate. Principle Investigator,       2005-2007, US$ 350,000
2. 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). 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).

Career History

2008 – Present Adjunct Professor at Georgia Tech2007 – Present Professor and Chair Regenerative Medicine, Institute of Biomedical Innovation, QUT2005 - 2007 Joint Appointment as Associate Professor (Tenure), Division of Bioengineering, Department of Orthopedic Surgery, National University of Singapore2001 - 2005 Joint Appointment as Assistant Professor, Division of Bioengineering, Department of Orthopedic Surgery, National University of Singapore1999 - 2001 Senior Research Fellow, National University of Singapore1998 - 1999 Managing Director, Medical Monitor gmbh1995 - 1998 Assistant Professor (part time), Department of Mechanical Engineering, University for Applied Science. Offenburg, Germany1995 - 1999 Hutmacher Implant Innovation (Self-Employed)1993 - 1994 Managing Director, BIOVISION gmbh1990 - 1994 Senior Lecturer (part time), Dept of Mechanical Engineering, University for Applied Science. Offenburg, Germany1989 - 1992 Senior Lecturer (part time), Dept of Mechanical Engineering, University for Applied Science. Offenburg, Germany1989 - 1992 Head of R&D Department, Biomaterials, G. Hug Gmbh1989 - 1989 R&D Engineer, Boehringer Mannheim