Bioreactors to Replace Animal Testing in Bone Research

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Our vision is to replace need for animal testing in bone research with lab-based bioreactor analyses of human tissue. The immediate benefit will be replaced animal burden for bone research and orthopaedic intervention development at technology readiness levels 1-4. The method will also lead to better interventions as treatments are optimised with human bone, sourced from patients with relevant demographics and disease history. Advancing interventions to promote favourable bone remodelling is important for the 200,000 people who require joint replacement, or the 70,000 that fracture their hip each year in the UK, with similar numbers affected worldwide.The research is timely: animal burden is growing as the field transitions from passive implants tested in cadavers, to orthobiologics, tissue engineered implants, drugs and active stimulation technologies that influences living tissue pathways. An appropriate preclinical test method is needed to facilitate the development and translation of these technologies to deliver improvements in patient care and socioeconomic benefit.The core idea that underpins the proposal is that tissue can stay viable for 1-24 hrs after being removed from the body; something that is widely accepted in the field of transplants. With bioreactor technology, we will keep the bone viable for weeks, allowing for novel interventions to be tested against viable human bone, in the lab.This research will investigate the sensitivity of bone bioreactors to tissue preparation methods and bioreactor settings to comprehensively characterise best practice for the novel approach. Then, we will conduct a direct validation against previous in vivo data, to quantify the extent to which the method can replace live animal testing. Finally, with the method validated, to build the 3Rs case for adoption, we will analyse the effect of species (animal vs human) on bone remodelling around implants. This would demonstrate the scientific benefits that could be gained from replacing animal testing with an alternative that is more relevant to humans.