Mechanical Stimulation in Bone-on-Chip Platforms: A Systematic Review of Osteogenic Responses in Medical and Dental...

Bone healing, remodeling, and pathology are strongly regulated by mechanical stimulation. However, conventional two-dimensional (2D) in vitro culture systems fail to reproduce the complex mechanical and biological microenvironment of human bone, limiting their translational relevance. In recent years, bone-on-chip (BoC) platforms, as part of the broader organ-on-chip (OoC) technology, have emerged as advanced microfluidic systems that enable the study of bone biology under dynamic and highly controlled conditions that more closely mimic in vivo physiology. This systematic review aimed to gather the available in vitro evidence on mechanically stimulated BoC models, with a particular focus on osteogenic differentiation outcomes and the technical characteristics underlying these platforms. Following a comprehensive literature search and structured data extraction, biological parameters (cell types, culture conditions, scaffolds), chip design and fabrication strategies, mechanical loading modalities, and assessment assays were systematically analyzed. Across the included studies, fluid shear stress was the most frequently applied mechanical stimulus and was generally associated with enhanced osteogenic differentiation compared with static cultures, although substantial heterogeneity was observed in loading protocols and outcome measures. Overall, this review provides a consolidated technical and biological overview of mechanically stimulated BoC systems and highlights key methodological considerations for future platform development. By integrating microengineering approaches with bone and stem cell biology, BoC models hold significant potential for advancing bone tissue engineering, mechanobiology research, and translational applications, including dentistry-related bone regeneration and biomaterial testing.