Advances in extracellular vesicle-based nanomedicine for regenerative orthopaedics

Abstract The increasing prevalence of bone and cartilage injuries presents a persistent clinical challenge in orthopaedic medicine. Current standard-of-care approaches and regenerative strategies, including cell-based therapies and conventional biomaterials, remain suboptimal due to their limited capacity to precisely modulate the complex cellular and molecular mechanisms governing cartilage repair, bone remodelling, and osseointegration. Extracellular vesicles (EVs), nature’s nanoscale mediators of intercellular communication, have recently emerged as powerful bioactive entities with immense potential to orchestrate tissue regeneration. This review critically examines the diverse and dynamic roles of EVs in orthopaedic repair, emphasizing their mechanistic contributions to osteogenesis, chondrogenesis, and osteochondral interface regeneration. We further highlight recent advances in bioengineering approaches designed to enhance EV therapeutic efficacy, including surface functionalization, cargo engineering, and biomaterial-based delivery systems. Finally, we discuss the advent of EV-mimetic nanoplatforms as next-generation therapeutics, underscoring their translational potential to overcome current clinical limitations. Collectively, this review highlights the transformative promise of EV-based and EV-inspired nanotechnologies in advancing the frontier of bone and cartilage regenerative medicine. Graphical abstract