The effect of mechanical stimuli on bone physiology: a systematic review of organ-on-a-chip models

Background: Mechanical stimuli are crucial regulators of bone formation. Organ-on-chip platforms offer dynamic in vitro environments for studying osteogenesis. Objective: To systematically review the effects of mechanical stimulation on osteogenic differentiation in bone-on-a-chip (BoC) platforms. Methods: A systematic review was conducted in accordance with PRISMA 2020. PubMed and Web of Science were searched up to June 2025. Studies were included if they used mechanical loading in BoC models and reported osteogenic outcomes. Data were extracted independently by two reviewers. Results: Nineteen in vitro studies were included. Mechanical stimuli, including fluid shear stress, compression, and electromagnetic fields, enhanced osteogenic markers such as ALP activity, mineral deposition, and osteogenic gene expression. The QUIN tool revealed medium risk of bias in most studies. Limitations: High heterogeneity in chip design, mechanical loading parameters, and cell types precluded meta-analysis. Conclusions: Mechanical stimulation effectively promotes osteogenesis in bone-on- chip systems, although standardization is necessary. Future models should incorporate real-time readouts and multi-lineage co cultures.