Rationale: Biomechanical computational modelling offers enormous potential for the replacement, refinement and reduction (3Rs) of animal experiments, however, their routine application in 3Rs is negligible. This project has two overarching goals: (1) to investigate the type and amount of experimental data required for musculoskeletal computer models to deliver accurate predictions, and (2) in doing so provide quantitative data on the current and future potential of models to contribute to the reduction, replacement and refinement (3Rs) of animal experiments in scientific research.
Plan of work and impact of our studies: To achieve this, we will use chewing (mastication) in rabbits as our model system. The data collected will be relevant to basic biological science fields and to the health and welfare of rabbits. We will collect a wealth of anatomical and physiological experimental data which will allow us to build, drive and validate the most comprehensive musculoskeletal computer models produced to-date. Our initial models will thus provide a best-case scenario for simulation accuracy. We will then incrementally reduce or average-out the resolution of input data given to the model and observe the effects on accuracy. This will tell us how individual input parameters affect accuracy and help the musculoskeletal research community identify which parameters do not need to be measured through experimentation in real animals to achieve specific thresholds of accuracy.
Animal welfare: The main aim of this research is to develop a general framework for the development, acceptance and application of computational models of hard and soft tissue cranial biomechanics to further drive forward their use in the replacement, refinement and reduction (3Rs) of animal experiments, having a direct impact on animal welfare. Within this research programme the surgical procedures and some of the associated experiment methods may cause moderate pain, harm, suffering or distress – e.g. during surgery or the feeding experiments. Animals will be checked for appearance and potential behaviour indicators of pain or distress and action taken as necessary. Appropriate group sizes are used to identify statistically significant differences between groups, whilst minimising the numbers of animals undergoing the protocol. Group sizes are constantly reviewed to ensure the minimum number of animals is used.
Read validating computer models of mastication non-technical summary (PDF).
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