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Bone grafting is one of the most common procedures performed in orthopaedic surgery. Annually all over the world approximately 2.2 million orthopaedic operations use bone grafts in one form or the other. Autologous bone grafts, i.e. bone harvested from the patient’s own body, has long been the “gold standard”. The most prevalent donor site is the iliac crest. The problems associated with it have been well documented, including donor site morbidity and restricted availability, especially if large quantities are required. There are a few commercially available bone graft substitutes but we still have nog found ani deal substitute for autologous bone graft. In this article, we will have a look at the different options available along with their characteristics, and see how they match up with the “gold standard”.
Dr Hendrik P. Delport works together with Prometheus a basic science laboratory to translate results of innovative research into usefull clinical applications.
Prometheus, the division of Skeletal Tissue Engineering of the K.U.Leuven, is an interdisciplinary initiative focusing on skeletal tissue engineering (TE) research and technology transfer, founded by the Divisions of Rheumatology, Orthopaedics, Biomechanics, Experimental Medicine and Endocrinology and Prosthetic Dentistry, and the Department of Metallurgy and Materials Engineering. The Prometheus platform runs 3 integrated programs:
(i) fundamental science related to stem cells and 3D tissue creation.
(ii) translation of scientific findings into a technological plan for manufacturing processes, quality and safety.
(iii) creation of blue prints for the clinical implementation of a bone TE therapy.
These 3 programs are divided into 6 research tracks that are coordinated by experts in the field and are supported by a broad technology platform and state-of-the-art infrastructure that is based on:
(i) adult stem cell protocols & gene therapy.
(ii) multiscale computational modelling from molecular, over cell and tissue, to patient level.
(iii) scaffold design, manufacturing and characterisation.
(iv) instrumented bioreactors.
(v) clinically relevant in vivo models.
(vi) a knowledge & technology network linked to clinical practice.
At present the Prometheus interdisciplinary research team consists of about 40 people, ranging from technicians, over PhDs, post-docs to orthopaedic surgeons and a management. The founding Prometheus scientists have discovered pathways that have been identified as critical in the formation of skeletal tissues, made contributions to the characterisation of stem/progenitor cells and to the clinical development and technology transfer of cell based therapies for skeletal repair, have extensive experience in clinical evaluation of new therapies and are experienced in project management of national and international projects related to bone tissue engineering and biomaterials. Part of these scientific achievements has been transferred into the spin-offTiGenix NV. The scientific success of this research group is indicated by the fact that the Prometheus scientists generated 70 unique peer-reviewed publicationsrelevant to skeletal TE in the last three years in high quality journals. This is reflected by an h-index on Thompson ISI of 50. Prometheus had 29 grantson skeletal regeneration ongoing in the last three years for a total of €5,43 million.
Translational research is a way of thinking about and conducting scientific research to make the results of research applicable to the population under study and is practised in the natural and biological, behavioural, and social sciences. In the field of medicine, for example, it is used to translate the findings in basic research more quickly and efficiently into medical practice and, thus, meaningful health outcomes, whether those are physical, mental, or social outcomes. In medicine in particular, governmental funders of research and pharmaceutical companies have spent vast amounts internationally on basic research and have seen that the return on investment is significantly less than anticipated. Translational research has come to be seen as the key, missing component. Translational research is another term for translative research and translational science, although it fails to disambiguate itself from forms of research that are not scientific (e.g., market research), which are currently considered outside its scope.
With its focus on removing barriers to multi-disciplinary collaboration, translational research has the potential to drive the advancement of applied science. An attempt to bridge these barriers has been undertaken particularly in the medical domain where the term translational medicine has been applied to a research approach that seeks to move “from bench to bedside” or from laboratory experiments through clinical trials to actual point-of-care patient applications. However, the term translational medicine is a misnomer, as medicine is not a science: it is the clinical practice of healing the given individual whereas science addresses principles and populations. This distinction is the primary reason that science needs to be translated at all. \"Translational medicine\" would best be termed \"Translational medical science\".
Comparison to basic research or applied research
Translational research is a paradigm for research alternative to the dichotomy of basic research and applied research. It is often applied in the domain of medicine but has more general applicability as a distinct research approach. It is also allied in practice with the approaches of participative science and participatory action research.
The traditional categorization of research identifies just two categories: basic research (also labelled fundamental or pure research) and applied research. Basic research is more speculative and takes a long time – often measured in decades – to be applied in any practical context. Basic research often leads to breakthroughs or paradigm-shifts in practice. Applied research on the other hand is characterised as being capable of having an impact in practice within a relatively short time, but would often represent an incremental improvement to current processes rather than delivering radical breakthroughs.
The cultural separation between different scientific fields makes it difficult to establish the multidisciplinary and multi-skilled teams that are necessary to be successful in translational research. Other challenges arise in the traditional incentives which reward individual principal investigators over the types of multi-disciplinary teams that are necessary for translational research. Also, journal publication norms often require tight control of experimental conditions, and these are difficult to achieve in real-world contexts.
Outside of the medical domain, this mode of research can be applied more generally where researchers seek to shorten the time-frame and conflate the basic-applied continuum to ‘translate’ fundamental research results into practical applications. It is of necessity a much more iterative style of research with low and permeable barriers and a great deal of interaction between academic research and industry practice. Practitioners help shape the research agenda in supplying what may be intractable problems to which applied research approaches will only offer incremental improvements.
Challenges in translational research
To flourish translational research requires a knowledge-driven ecosystem, in which constituents generate, contribute, manage and analyze data available from all parts of the landscape. The goal is a continuous feedback loop to accelerate the translation of data into knowledge. Collaboration, data sharing, data integration and standards are integral. Only by seamlessly structuring and integrating these data types will the complex and underlying causes and outcomes of illness be revealed, and effective prevention, early detection and personalized treatments be realized.
Translational research requires that information and data flow from hospitals, clinics and participants of studies in an organized and structured format to repositories and research-based facilities and laboratories. Furthermore, the scale, scope and multi-disciplinary approach that translational research requires means a new level of operations management capabilities within and across studies, repositories and laboratories. Meeting the increased operational requirements of larger studies, with ever increasing specimen counts, larger and more complex systems biology data sets, and government regulations, precipitates an informatics approach that enables the integration of both operational capabilities and clinical and basic data. Most informatics systems in use today are inadequate in terms of handling the tasks of complicated operations and contextually in data management and analysis.
Definitions of translational research
Translational research is a new and rapidly evolving domain. As such, the definition is bound to evolve over time. Generally speaking, the primary goal of “translational” research is to integrate advancements in molecular biology with clinical trials, taking research from the “bench-to-bedside”.
Websites that help to define translational research:
NIH Roadmap Definition
American Journal of Translational Research
American Journal of Translational Research
Translational Research Informatics
Clinical and Translational Science
Translational Medicine Research Collaboration
Center for Translational Injury Research
American Journal of Translational Research
Center for Comparative Medicine and Translational Research
Translational Research Institute for Metabolism and Diabetes
1. Feldman, A. Does Academic Culture Support Translational Research? CTS: Clinical and Translational Science 2008;1(2):87-88
2. Goldblatt EM, Lee WH. From bench to bedside: the growing use of translational research in cancer medicine. Am J Transl Res 2010;2(1):1-18
3. Woolf SH. The Meaning of Translational Research and Why It Matters. JAMA 2008;299;211-213
The mission of Prometheus, the division of Skeletal Tissue Engineering of the K.U.Leuven (www.kuleuven.be/prometheus), is to develop robust and clinically relevant Tissue Engineering concepts for skeletal applications. Therefore Prometheus runs 3 integrated programs, namely (i) fundamental science related to stem cells and 3D tissue creation, (ii) translation of scientific findings into a technological plan for manufacturing processes, quality and safety and (iii) creation of blue prints for the clinical implementation of a bone TE therapy. These 3 programs are divided into 6 research tracks. One of these research tracks focuses on the development of clinically relevant animal models and delivering pre-clinical proof-of-concept to enable clinical translation, the latter in particular for the treatment of non-healing bone defects. This research track is coordinated by a team of orthopaedic surgeons (Prof. Johan Lammens, Dr. Johan Vanlauwe, Dr. Hendrik Delport and Dr. Armand Laumen).
Prometheus has pre-clinical proof-of-concept for healing large bone defects using ‘engineered bone’ based on periosteal derived stem cells. Prometheus wants to bring this ‘living’ implant concept for bone regeneration into the clinic. Thepre-clinical data in 2 critical size tibial defect models, showing robust and functional healing, convinced the orthopaedic surgeons to acquire additional and pivotal pre-clinical data to start a clinical transfer. The translation will initially focus on atrophic non-unions as these fractures are an unmet clinical need and represent a major debilitating condition for patients.
Translational Research in Europe Applied
Technologies for OsteoArthritis
TREAT-OA is a large-scale collaborative, integrated, trans-disciplinary project to address the need for better treatment and diagnostics for osteoarthritis, the most common cause of disability in Europe. The consortium members are world-class expert investigators from the US, Asia and Europe who will contribute to TREAT-OA biospecimens and clinical data from their own cohorts.
The gene driven approach aims to provide new therapeutic targets as well as tools to select patients which will be most likely to respond to those therapies effectively. It will also deliver a comprehensive technology platform with a focus on gaining new insights into the development and progression of human OA. The goal is to identify diagnostic and prognostic genetic markers for disease risk and progression and potential therapeutic targets. Currently there are no drugs that can cure, reverse or halt the disease. Nor are there yet reliable clinical biochemical markers for diagnosis or prognosis which is an impediment to the management of OA, the development of disease modifying drugs and increases the cost of therapeutic trials.This is the largest study of its kind that will address the generalisability and utility of genetic and biochemical risk factors throughout the EU and establish animal models for OA, which will help in further elucidating the pathogenetic mechanisms and also in the evaluation of intervention strategies that will be aimed at delaying the onset of the disease and in improving the quality of life.
The key objectives of TREAT-OA are to:
The novel pathways in disease aetiology discovered will translate into novel drug targets and protein therapeutics for OA. The development of in vitro and in vivo assays will provide a comprehensive technology platform enabling the discovery and development of disease modifying drugs for OA. TREAT-OA will also make a major impact on the disease via a diagnostic panel of genes and biochemical markers for selecting severe cases and individuals who will experience rapid progression of their disease.