Fatemeh Tajafrooz, Sepehr Ghofrani, Fatemeh Sadeghghomi, Ali El Hadi Chamas, Narges Rahimi, Arshia Mirakhor, Mohammad Hosseini Hooshiar, Amir Raee
Bone deficiencies are a major clinical issue for millions worldwide, with challenges to treatment because of donor site morbidity, immunological rejection, and limited integration. Exosomes are endogenously secreted extracellular vesicles and have potential as cell-free therapeutics. Exosomes derived from mesenchymal stromal cells (MSCs), bone marrow cells, and other cell-derived exosomes transmit bone morphogenetic proteins, growth factors, and immunoregulatory microRNAs to initiate osteogenic pathways. These exosomes stimulate and orchestrate vascularization and bone formation. Engineering strategies such as cargo optimization, surface functionalization, and cellular preconditioning further augment therapeutic promise. Clinical translation for exosome therapy has hurdles in manufacturing standardization and regulatory routes.