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Collagen is the most widely used substratum in cell culture and biomaterials applications. In this chapter, we describe a simple procedure to isolate collagen, which can be employed to a wide range of tissue sources, and subsequently use it to study the collagen crosslinking and stabilization abilities of various compounds. The protocol is designed for a multi-well format assay and thus can be used for simultaneous assessment of multiple number of compounds and can be easily adapted to a high-throughput screening setup.