3Rs-Centre Utrecht Life Sciences

Faculteit Dierengeneeskunde
 
December 2016
Whole-joint bio-mechano-reactor accelerates research on osteoarthritis and reduces use of animals

At the Department of Rheumatology of the University Medical Center Utrecht (UMCU), dr. Simon Mastbergen focuses his research activities on joint tissue damage. In order to study the progress and possible treatments of degenerative joint diseases, in particular osteoarthritis, he has initiated the development of a whole-joint bio-mechano-reactor. The model is currently at the level of a working prototype, and enables the evaluation of many different pathways in the development of osteoarthritis. When validated, it has the potential to drastically reduce the number of animals used in this field of biomedical research.

The need for the development of a new model to study osteoarthritis resulted from the shortcomings of the models currently available. In vitro models, though often used, have their limitations in this particular field of research; the absence of mechanical and biological components that interact with the joint tissues when in a natural setting, is not easy to overcome. In order to fill up this gap, in vivo models are used to appreciate the complete set of interacting components. However, the disadvantages of animal models in this field are numerous. For example, when studying arthritis or other joint-related defects, the joint should ideally be observed throughout the different stages of development of the disease. In that regard, a lot of animals have to be sacrificed to reveal what happens in this ‘black box’ on each point in time1. Apart from the fact that this is undesirable from an ethical point of view, this also tends to make the research quite expensive. Moreover, the exact biomechanical conditions that a joint experiences is difficult to monitor in an in vivo experiment. Furthermore, inducing osteoarthritis in animals is considered a painful process. Mastbergen also emphasizes that rodents are less ideal models for joint damage research, since the structure of rodent cartilage differs in their matrix-cell ratio from human cartilage. The introduction of the whole-joint bio-mechano-reactor tackles all of these issues at once, providing a cost-efficient model with high scientific and translational value. Besides, once this reactor is appropriately validated, the number of animals used in osteoarthritis research can be strongly reduced, possibly by 50% or more.

Successful whole joint culturing
It is envisioned that the bio-mechano-reactor takes into account all components that influence the function and biology of the joint. This allows for individual modulation of multiple biochemical and biomechanical conditions. A whole dog stifle joint, equivalent to the human knee, is placed into the reactor, that contains a medium comprising as much as possible the biological compounds as present in the synovial fluid in the in vivo environment. Subsequently, the biomechanical conditions and the concentration of surrounding compounds can be controlled, enabling investigation of the influence of manipulations at each desired location in the joint. The latter is an important factor, since the biomechanical characteristics of the cartilage tissue are for instance location and direction dependent. This is often ignored for sake of study complexity. Although the bone tissue dies in the reactor due to lack of blood flow, its supporting function for the cartilage tissue is preserved. Furthermore, the cartilage remains viable since it does not contain blood vessels. Thereby cell activity can still be measured, thanks to the properties of the culture medium present in the reactor.


The bio-mechano-reactor (picture taken by dr. Simon Mastbergen).

Future perspective: validated, flexible model
Dr. Mastbergen works on the development of the reactor together with PhD candidate Thijmen Struik. The aim of their project is to further develop the bio-mechano-reactor into a model that is suitable for studying both the development and treatment of osteoarthritis. However, the first step will be the validation of the model. Besides, the reactor should ideally be compatible with the joints of a variety of species. Currently, the scientists mainly use canine stifle joints, because the anatomy of this joint strongly resembles the human knee. However, canine stifle joints are expensive and relatively difficult to obtain. Therefore, they would like to make the reactor compatible for other species, for example pig stifle joints. In that way, they can use pigs that were already used in other experiments, with the result that fewer animals are sacrificed for research on osteoarthritis. The implementation of this model serves as a promising progression in medical science.
 
Dr. Simon Mastbergen is associate professor in Tissue Degeneration and Regeneration. The Rheumatology Department has no published article on the bio-mechano-reactor yet. However, an abstract can be found online2.

  1. Akhtar, R., & Derby, B. (2015). Introduction: aging and the mechanical properties of tissues. In Mechanical properties of aging soft tissues (pp. 1-6). Springer International Publishing.

  2. Struik, T., Peeters, L. H., Lafeber, F. P., & Mastbergen, S. C. (2015). AB0108 Reproduction of Joint-Specific Biomechanics for Application in a Whole Canine Stifle Joint Bioreactor.Annals of the Rheumatic Diseases74(Suppl 2), 926-927.