Idiopathic pulmonary fibrosis from a multiscale mechanobiology perspective: Mechanisms and future therapeutic prospects.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease that induces irreversible fibrosis and architectural remodeling. Traditional inflammation-based theories fall short in explaining its pathological processes, regional heterogeneity, and spatially biased lesion distribution. Recent studies have highlighted the critical role of biomechanical microenvironment, ranging from the molecular and cellular level to the whole-organ scale, in driving fibrotic progression. This review adopts a multiscale biomechanical perspective for understanding IPF pathogenesis, integrating molecular, cellular, tissue, and organ-level mechanisms. We summarize recent advances in IPF research from five key biomechanical perspectives: mechanotransduction, mechanical memory, extracellular matrix (ECM) stiffening, strain-induced fibroblast activation, and the spatial propagation of fibrosis. We further explore therapeutic strategies targeting mechanical signaling pathways and discuss the integration of machine learning and physics-informed neural networks (PINNs) for interpretable, physiology-constrained modeling. This review aims to provide a new mechanobiological perspective for understanding and intervening in IPF.