Skeletal organoids.

Abstract

The skeletal system, composed of bones, muscles, joints, ligaments, and tendons, serves as the foundation for maintaining human posture, mobility, and overall biomechanical functionality. However, with ageing, chronic overuse, and acute injuries, conditions such as osteoarthritis, intervertebral disc degeneration, muscle atrophy, and ligament or tendon tears have become increasingly prevalent and pose serious clinical challenges. These disorders not only result in pain, functional loss, and a marked reduction in patients' quality of life but also impose substantial social and economic burdens. Current treatment modalities, including surgical intervention, pharmacotherapy, and physical rehabilitation, often do not effectively restore the functionality of damaged tissues and are associated with high recurrence rates and long-term complications, highlighting significant limitations in their efficacy. Thus, there is a strong demand to develop novel and more effective therapeutic and reparative strategies. Organoid technology, as a three-dimensional micro-tissue model, can replicate the structural and functional properties of native tissues in vitro, providing a novel platform for in-depth studies of disease mechanisms, optimisation of drug screening, and promotion of tissue regeneration. In recent years, substantial advancements have been made in the research of bone, muscle, and joint organoids, demonstrating their broad application potential in personalised and regenerative medicine. Nonetheless, a comprehensive review of current research on skeletal organoids is still lacking. Therefore, this article aims to present an overview of the definition and technological foundation of organoids, systematically summarise the progress in the construction and application of skeletal organoids, and explore future opportunities and challenges in this field, offering valuable insights and references for researchers.