Musculoskeletal Organs-on-Chips: An Emerging Platform for Studying the Nanotechnology-Biology Interface

Nanotechnology-based approaches are promising for the treatment of musculoskeletal (MSK) disorders, which present significant clinical burdens and challenges, but their clinical translation requires a deep understanding of the complex interplay between nanotechnology and MSK biology. Organ-on-a-chip (OoC) systems have emerged as an innovative and versatile microphysiological platform to replicate the dynamics of tissue microenvironment for studying nanotechnology-biology interactions. This review first covers recent advances and applications of MSK OoCs and their ability to mimic the biophysical and biochemical stimuli encountered by MSK tissues. Next, by integrating nanotechnology into MSK OoCs, cellular responses and tissue behaviors may be investigated by precisely controlling and manipulating the nanoscale environment. Analysis of MSK disease mechanisms, particularly bone, joint, and muscle tissue degeneration, and drug screening and development of personalized medicine may be greatly facilitated using MSK OoCs. Finally, future challenges and directions are outlined for the field, including advanced sensing technologies, integration of immune-active components, and enhancement of biomimetic functionality. By highlighting the emerging applications of MSK OoCs, this review aims to advance the understanding of the intricate nanotechnology-MSK biology interface and its significance in MSK disease management, and the development of innovative and personalized therapeutic and interventional strategies.