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Bone tissue engineering (TE) has traditionally applied biological components such as stem cells or growth factors in combination with biomaterial scaffolds to achieve a regenerative response. Although many positive outcomes have been observed pre-clinically using this approach, some significant challenges remain. Over the last two decades it has become increasingly clear that stem cells exert many of their biological effects indirectly through the action of paracrine factors. These findings have called into question the long-accepted view of direct stem cell engraftment and differentiation, instead highlighting the importance of secreted factors such as extracellular vesicles (EVs) in the local tissue microenvironment. This is beginning to change the landscape of TE, with a growing interest in applying EVs to augment or even replace existing cellular approaches. This chapter will provide a balanced view of the benefits of applying EVs in bone TE and highlight the current state-of-the-art approaches for enhancing their biotherapeutic effects. Lastly, it will identify key parameters that need to be addressed to ensure effective reproducibility and translation.

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