Research & Development
Stem cell biology & cell based therapies/ Moddeling TE environment & processes / Signalling angio & osteogenesis/ Clinically relevant animal models & pre-clinical planning/ Scaffolds & bioreactors/ In vitro & in vivo screeningStem cell biology & cell based therapies
Coordinators Prof. Frank Luyten & Dr. Scott Roberts
The use of mesenchymal stem cells (MSCs) in combination with a scaffold is a promising approach for repair of skeletal tissues, in particular for bone. There is increasing evidence that MSCs are present in wide variety of tissues such as synovium, cartilage, periosteum, muscle and bone marrow. Currently, our research group is focusing on the use of periosteum derived cells (HPDCs) in bone engineering, because periosteum is known to contribute in a direct way to fracture healing in vivo. In parallel, bone marrow derived cells and multipotent adult progenitor cells (MAPCs) are explored in bone formation models. To bring bone forming cells from bench to bedside, cell populations need to be well characterized to guarantee appropriate cell behaviour with respect to potency, efficacy and toxicity, when implanted in human. Preferentially, the cell characterization should be related to the biological outcome in vivo. Such predictive markers may be found based on the signalling pathways required for bone formation by the cells in vivo.
Modelling TE environment & processes
Coordinators Prof Hans Van Oosterwyck & Prof. Lies Geris
Cell and tissue fate are determined by the micro environmental signals (such as biochemical and biomechanical) to which they are exposed. Quantification of these signals and the response to them is crucial in order to gain a better understanding of cell and tissue dynamics, relevant for bone regeneration and engineering. Computational models are complementary to measurements, as they allow quantification of signals that are otherwise hard to measure. Furthermore, models can be created to try to predict cell and tissue fate based on environmental signals. Such models can increase our quantitative understanding of the TE environment and can be used to try to optimise and control this environment.
Signalling angio & osteogenesis
Coordinator: Prof. Geert Carmeliet
Bone TE seems a promising approach in the therapy of large bone defects. However, the use of solely an allograft or synthetic scaffold is at present not superior to an autograft. To improve the healing of structural bone defects we aim to combine an appropriate cell source with angiogenic and osteogenic growth factors, applied to an allograft or a synthetic scaffold. In addition, as hypoxia is a critical factor at the start of fracture healing we will investigate the role of hypoxia signalling in bone repair. This latter study may reveal potential additional therapeutic targets.
Clinically relevant animal models & pre-clinical planning
Coordinators: Prof. Johan Lammens, Dr. Johan Vanlauwe , Prof. Evert Schepers & Dr. Marina Maréchal
The participation of orthopaedic surgery and dentistry in the Prometheus project is based on a clinical need for bone TE. Clinicians are in the best position to define the problems doctors and patients are faced with daily. As such they help to determine the ultimate goal the research should aim at. Too often excellent research does not exceed the level of the laboratory as there is a lack of well defined applications.
The rationale for large animal models is the problem of up scaling. The translation of laboratory research to the in vivo large animal model is an essential and crucial step towards potential human applications. Although good results may be clear from in vitro and small size species such as mice and rats, this is no guarantee for effectiveness once the dimensions are multiplied by a factor 10 or 100. Cells have roughly the same dimensions in all species but the distances they have to travel are enormously different if a 1 mm defect in a mouse is compared with a 100 mm bone loss in a human tibia. To our opinion this ‘mathematical mismatch’ seems underestimated in many actual bone TE projects.
Coordinator: Dr. Jan Schrooten, Prof. Jennifer Patterson & Prof. Jean-Marie Aerts
Several biomaterials have proven their potential for bone regenerating applications on a lab scale, but up till now they only had a limited penetration into clinical practice mostly due to the lack of suitable production techniques needed to produce controllable 3D environments for osteogenic cells. The effect of materials on biology needs to be controlled down to the cellular level. This implies that scaling up to clinical volumes may not introduce additional variation. This can be guaranteed be using consistently produced scaffolds by applying additive techniques for the bulk production (supra-cellular level) and specific surface engineering to functionalise the scaffold surface (cellular and sub-cellular level).
Together with the scaffold the bioreactor forms the controlled 3D environment for cells. The combined use will allow performing a majority of experiments on a small scale and then scale up by use of the bioreactors, modelling tools and animal models. The use of bioreactors allows monitoring and quantitative control of cell behaviour and thus provides a technological mean to scale up in a controlled manner and establish fundamental inside on the interaction between bone growth stimulating factors. On the other hand it will assist TE to become economically feasible. Once a 3D environment is under control on a lab scale it needs to transferred to an industrial setting (specification, automation and standardisation).
In vitro & in vivo screening
Coordinator: Dr. Jan Schrooten
Prometheus provides in vitro and in vivo screening services for bone growth stimulating components (cells, materials, signals and combinations of the above) using its bioreactor set-ups and in vivo models. To facilitate these screenings, either for network partners or for third parties, standard operating procedures are developed.