Engineered extracellular vesicles: Regulating the crosstalk between the skeleton and immune system

Osteoimmunology has gained momentum in recent years, focusing on the crosstalk between the skeleton and the immune system. Extracellular vesicles (EVs) are nanoscale vesicles that are potential candidates for cell-free tissue regeneration strategies. They may be used for repairing damaged tissues and regulating the body's immune system and bone-related metabolic activities. Because of the ability of EVs to deliver bioactive signals and mediate intercellular communication, they can decipher the complex mechanisms of interaction within the “osteoimmune system” at the molecular level. To address the lack of targeting ability caused by vesicle heterogeneity in the clinical applications of EVs, these nanoscopical entities may be modified by bioengineering techniques to optimize the interaction between bone repair and immunomodulation for improving treatment efficacy, specificity and safety. In the present review, the endogenous properties that make EVs natural delivery agents are outlined. Properties that may be improved by bioengineering are highlighted. The therapeutic applications of EVs in the rehabilitation of bone defects are discussed. The opportunities and challenges that need to be addressed for translating this field of research into clinical practice are brought into perspectives.