Research Platforms and Recent Advances of Mechanoimmunology

Unlike most tissue-resident cells that inhabit relatively homeostatic mechanical microenvironments, immune cells encounter diverse mechanical cues as they circulate throughout the body and transmigrate across tissue barriers. Mechanical stimuli have emerged as fundamental upstream regulators of both innate and adaptive immune responses. Mechanotransduction processes governed by core biomechanical sensors and effectors, including Piezo1, TRPV4, and YAP/TAZ, have recently attracted escalating research attention across immunological and mechanobiological fields. Notably, cellular mechanosensing is intrinsically context-dependent, shaped by the interplay between local mechanical properties and biochemical cues within tissue microenvironments. As a result, mechanoregulated immune phenotypes and functional outputs are highly sensitive to the experimental configurations of preclinical models. In contrast to previous reviews that mainly outline mechanotransduction signaling cascades, this review systematically categorizes prevalent biomechanical research platforms, detailing their technical specifications and key parametric characteristics, while contextualizing the mechanical regulation of immune behaviors within specific experimental frameworks. STATEMENT OF SIGNIFICANCE: Mechanoimmunology has revealed that mechanical forces are fundamental regulators of immune cell function, yet the field is plagued by contradictory findings arising from inconsistent platform parameterization. This review provides the first systematic classification of five major biomechanical research platforms - 2D hydrogel systems, 3D matrix models, microfluidic devices, single-molecule force spectroscopy, and in vivo genetic models - detailing their technical specifications, parametric boundaries, and experimental contexts. By anchoring immune mechanobiological conclusions to specific platform parameters, we establish a framework for resolving apparent phenotypic contradictions and standardizing cross-study comparisons. This context-aware approach directly informs the rational design of immunomodulatory biomaterials with tunable mechanical properties, bridging biomaterials engineering and immune cell biology for applications in tissue repair, cancer immunotherapy, and regenerative medicine.