Fibrosis is a pathological process characterized by excessive deposition of extracellular matrix (ECM) and tissue stiffening, leading to organ failure and representing a common end-stage manifestation of numerous chronic diseases. The immune system plays a pivotal role in fibrosis progression, where various immune cells participate in the initiation and development of fibrosis by secreting various cytokines and regulating the balance between inflammation and repair. Mechanical signals such as ECM stiffness, fluid shear stress, and tissue viscoelasticity also significantly contribute to fibrotic progression. Alteration of mechanical microenvironment in fibrotic tissues not only influences fibroblast activation and ECM remodeling but also modulates immune cell recruitment, polarization, and function, thereby forming a pro-fibrotic positive feedback loop involving mechanical, immunological, and fibrotic responses. Conventional models, such as two-dimensional (2D) cell cultures and animal models, exhibit considerable limitations in recapitulating such complex cellular interactions. Recent advances in organoid and organ-on-a-chip (OoC) technologies provide powerful tools to better mimic in vivo multicellular crosstalk, mechanical microenvironment, and immune responses, facilitating the understanding of fibrotic mechanisms and screening of anti-fibrotic drugs. This review summarizes the pathological bases of immune-related fibrotic diseases, alterations in mechanical microenvironment, interactions between immune cells and fibrotic tissues, and highlights the application and prospects of organoid and OoC platforms in fibrosis research involving mechanical and immunological factors.
Song et al. (Mon,) studied this question.