Abstract
Optimal exploitation of biological matrices for tissue engineering is hindered by incomplete understanding of their dynamic nature and the multidimensional complexity of their biomaterial properties. The unmet need in the field warrants investigation of the natural extracellular matrix as a complete and defined biomaterial. Here, we utilized two murine models to characterize native extracellular matrix alterations during inflammatory disease development. Biophysical and biochemical data integration allowed us to map discrete states unique in morphology, stiffness, and protein and metabolite compositions, which correlated with elevated matrix-degrading enzyme activity. Through the lens of this analysis we uncovered a silent pre-symptomatic tissue state, exhibited as a multidimensional biomaterial footprint, and matrix-derived clinically relevant biomarkers. Our holistic analysis showcases the native extracellular matrix as a dynamic and ultra-sensitive sensor of discrete tissue states. Successful matrix implementation in material research and therapeutics must be fine-tuned in a state-specific manner to ensure their desired bioactivity.