Hutmacher, Dietmar - Queensland University of Technology - Biomedical engineering and medical physics discipline

个人简介

Career History 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

研究领域

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.

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Papadimitropoulos A, Friess S, Beckmann F, Salmon P, Riboldi S, Hutmacher D, Martin I, Muller B, (2008) Comparative study of desktop- and synchrotron radiation-based micro computed tomography analyzing cell-seeded scaffolds in tissue engineering of bone, Proceedings: Developments in X-Ray Tomography VI (SPIE 7078) p1-11 Lam CX, Olkowski R, Swieszkowski W, Tan KC, Gibson I, Hutmacher D, (2008) Mechanical and in vitro evaluations of composite PLDLLA/TCP scaffolds for bone engineering, Virtual and Physical Prototyping p193-197 Peister A, Porter BD, Kolambkar YM, Hutmacher D, Guldberg RE, (2008) Osteogenic differentiation of amniotic fluid stem cells, Bio-Medical Materials and Engineering p241-246 Ekaputra AK, Prestwich GD, Cool SM, Hutmacher D, (2008) Combining electrospun scaffolds with electrosprayed hydrogels leads to three-dimensional cellularization of hybrid constructs, Biomacromolecules p2097-2103 Zhou Y, Hutmacher D, Sae-Lim V, Zhou Z, Woodruff M, Lim TM, (2008) Osteogenic and adipogenic induction potential of human periodontal cells, Journal of Periodontology p525-534 Lam CX, Hutmacher D, Schantz J, Woodruff MA, Teoh S, (2009) Evaluation of polycaprolactone scaffold degradation for 6 months in vitro and in vivo, Journal of Biomedical Materials Research Part A p906-919 Zhang H, Burdet E, Poo AN, Hutmacher D, (2008) Microassembly fabrication of tissue engineering scaffolds with customized design, IEEE Transactions on Automation Science and Engineering p446-456 Dombrowski C, Song SJ, Chuan P, Lim X, Susanto E, Sawyer AA, Woodruff MA, Hutmacher D, Nurcombe V, Cool SM, (2009) Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells, Stem Cells and Development p661-670 Reichert JC, Saifzadeh S, Wullschleger MA, Epari DR, Schuetz M, Duda G, Schell H, van Griensven M, Redl H, Hutmacher D, (2009) The challenge of establishing preclinical models for segmental bone defect research, Biomaterials p2149-2163 Sawyer AA, Song SJ, Susanto E, Chuan P, Lam CX, Woodruff MA, Hutmacher D, Cool SM, (2009) The stimulation of healing within a rat calvarial defect my mPCL-TCP/collagen scaffolds loaded with rhBMP-2, Biomaterials p2479-2488