Unraveling the Mechanical Microenvironment in Pulmonary Fibrosis: From Pathogenesis to Targeted Therapy

Pulmonary fibrosis (PF) is a chronic, progressive, and fatal disease characterized by lung tissue destruction and scar formation, with conventional treatments unable to halt its progression. This study examines the mechanical microenvironment in PF, emphasizing its role in pathogenesis, including altered matrix stiffness, disrupted mechanical signal transduction via mechanosensitive ion channels (e.g., Piezo1, TRPV4) and pathways (e.g., YAP/TAZ, TGF-β/Smad), and its relevance to biomaterial design and precision-targeted therapy. This study highlights biomaterials such as photoresponsive hydrogels with tunable stiffness and RGD-modified peptide hydrogels that modulate cell–extracellular matrix (ECM) interactions, along with targeted therapies including ion channel inhibitors and pathway antagonists. Collectively, these insights lay the groundwork for mechanics-based treatments and functional biomaterials, advancing precision regenerative medicine for PF.