Mechano-activated Extracellular Vesicle Based Repair of Bone

ended

Every 30 seconds a person suffers an osteoporosis-related bone fracture in Europe, resulting in significant morbidity, mortality and healthcare costs estimated at €36billion annually. Current anti-catabolic therapeutics are associated with severe side effects and are purely preventative, while the only anabolic treatment plateaus at 6 months. This has resulted in a crisis in osteoporosis treatment. Therefore, the aim of EVERBONE is to develop and commercialise a new anabolic multitargeted medicinal product for bone regeneration that mimics the beneficial effects of physical exercise, by recruiting endogenous cells to promote angiogenesis, osteogenesis and bone formation. Building on the discovery that osteocyte-derived mechanically activated extracellular vesicles (MAEVs) mediate the anabolic bone forming response to physical exercise, this project will develop novel bioreactor systems to increase MAEV yield in vitro and scale up for clinical use. Secondly, it will identify a standard mechanical conditioning procedure to generate optimised angiogenically and osteogenically primed MAEVs. Finally, preclinical evaluation of MAEV treatment will be performed in a model of osteoporosis and bone healing, whereby it is expected that MAEVs will localize to bone and mobilise endogenous endothelial and stem cell populations to enhance bone regeneration in osteoporosis and improved healing rates in bone defects. This regrowth of bone will overcome current limitations of anti-resorptive treatments, reducing the risk of fracture and thus the financial burden of treatment. The project will leverage the applicants experience in bone mechanobiology to develop a new product with significant commercial potential. Therefore, the impact of EVERBONE will be multifaceted: it will transform how osteoporosis is treated, it will create economic value through the commercialisation of IP, and most importantly it will improve patient experience and their long-term health and well-being.