Bone‐a‐Petite: Engineering Exosomes towards Bone, Osteochondral, and Cartilage Repair

Abstract Recovery from bone, osteochondral, and cartilage injuries/diseases has been burdensome owing to the damaged vasculature of large defects and/or avascular nature of cartilage leading to a lack of nutrients and supplying cells. However, traditional means of treatment such as microfractures and cell‐based therapy only display limited efficacy due to the inability to ensure cell survival and potential aggravation of surrounding tissues. Exosomes have recently emerged as a powerful tool for this tissue repair with its complex content of transcription factors, proteins, and targeting ligands, as well as its unique ability to home in on target cells thanks to its phospholipidic nature. They are engineered to serve specialized applications including enhancing repair, anti‐inflammation, regulating homeostasis, etc. via means of physical, chemical, and biological modulations in its deriving cell culture environments. This review focuses on the engineering means to functionalize exosomes for bone, osteochondral, and cartilage regeneration, with an emphasis on conditions such as osteoarthritis, osteoporosis, and osteonecrosis. Finally, future implications for exosome development will be given alongside its potential combination with other strategies to improve its therapeutic efficacy in the osteochondral niche.