Collagen Remodelling in Fibrotic Pathologies: Insights from Fourier Transform Infrared Imaging Spectroscopy

Fibrotic diseases are often characterized by excessive and disorganized deposition of extracellular matrix that progressively replaces functional tissue. In fibrosis, collagen, the dominant matrix protein, is not simply over-produced but qualitatively altered in the fibrillar organization, cross-linking density, and molecular conformation. Conventional histology reports how much collagen is present but provides little information on its molecular quality. Fourier Transform Infrared Imaging (FTIRI) spectroscopy addresses this gap: it is a label-free, non-destructive analytical technique that returns spatially resolved biochemical information directly from histological sections. This narrative, critically appraised review integrates collagen biology and fibrogenic mechanisms with a critical account of FTIRI methodology, from sample preparation to validation, and surveys the FTIRI evidence for collagen remodelling in uterine, pulmonary, hepatic, cardiac, renal, dermal, and tumour-associated fibrosis. Across organs, the peaks at 1284, 1240, and 1204 cm−1 (ascribable to the Amide III components) consistently discriminate collagen-rich fibrotic tissue from surrounding parenchyma, whereas conformational descriptors diverge in an organ- and stage-specific manner. Collagen abundance mapping is comparatively mature, whereas inferences on secondary structure and cross-linking remain method-dependent and lack independent biochemical validation. The main barriers to translation are small cross-sectional cohorts, non-standardized workflows, and validation designs vulnerable to information leakage.