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We propose a unifying mechanobiological framework in which chronic injury promotes fibroblast activation and ECM remodeling, whereas the stiffened and remodeled ECM feeds back through integrins, mechanosensitive ion channels, collagen receptors, and Hippo\u2010YAP\/TAZ signaling to sustain fibrogenesis. Regulation of this process is governed by bidirectional feedback between cellular signaling and the matrix's physical properties across organs such as the lung, heart, liver, and kidney. This narrative review article presents recent advances in understanding mechanisms of cell\u2013cell and ECM communication, paratensile signaling, mechanical feedback loops, cellular crosstalk and secretomes, quantitative therapeutic thresholds, and translational strategies for tissue remodeling. These developments collectively offer promising insights for the development of novel pharmacological agents targeting mechanotransduction pathways, ECM normalization, and cell\u2010specific sensitization. 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