Exosomal Interventions in Bone and Osteochondral Repair: Mechanisms and Outcomes.

Critically sized bone defects remain a global health and economic burden, and biomaterials associated with stem cell therapy have been widely applied as a significant strategy for bone regeneration. Due to limitations related to cell survivability, immune rejection, and transplantation at the defective bone site, the improved therapeutic outcomes of stem cells are achieved through paracrine actions, which involve the secretion of extracellular vesicles (EVs) and/or other factors. Ultra-small, nano-sized exosomes (Exos) of endosomal origin have demonstrated promising potential for bone regeneration through partially revealed intercellular communication. However, the real-time feasibility before clinical trials remains unknown. The current report aims to provide an overview of the various stem cell-derived exosomes in treating bone and cartilage defects, including osteoarthritis (OA) and osteochondral defect (OCD), and optimize the yield of Exos with enhanced tissue engineering potentials. Additionally, the encapsulation of Exos with various bioactive molecules to enhance therapeutic efficacy, their functionalization with biocompatible scaffolds to promote sustained release in the defective cellular microenvironment, and the molecular functions of Exos were investigated.