Idiopathic pulmonary fibrosis (IPF) is a chronic lung scarring disease with dismal survival. The TGF-?₁-activated, alpha-smooth muscle actin (?-SMA)-positive myofibroblasts are the effector cells in IPF and deposit a collagen-rich extracellular matrix (ECM). Collagen accumulation does not simply represent a consequence of abnormal wound healing, but evidence indicates that the ECM can signal to influence disease progression. DDR1 and DDR2 are receptor tyrosine kinases activated by collagen. Multi-kinase DDR inhibitors have shown anti-fibrotic effects in mice, but a role for the DDRs in lung fibrosis is incompletely elucidated. We hypothesise that the DDRs contribute to lung fibrogenesis by impacting fibroblast function, notably collagen synthesis. Using high-content immunofluorescence, dual DDR1/2 siRNA-mediated knockdown had no effect on TGF-?₁-induced collagen I deposition or ?-SMA expression, compared to non-targeting siRNA control (siNT) cells, following acute TGF-?₁ stimulation (48 hours). Optimisation of a chronic in vitro fibrotic model with macromolecular crowding, allowed the establishment of a collagen I matrix in vitro. After myofibroblast exposure to the matrix, dual DDR1/2 siRNA-mediated knockdown significantly reduced pro-collagen levels (based on hydroxyproline quantification in cell supernatants) by 30%, compared to siNT. In this model, myofibroblasts restimulated with TGF-?₁ downregulate COL1A1 and ACTA2, following dual DDR1/2 knockdown. Overall, this project extends our understanding of the potential contribution of the DDRs to fibrogenesis and proposes a chronic fibrotic model to enable the future identification of targets for therapeutic exploration.