1-Ethyl-3[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) treatment changes the biophysical and biochemical properties of collagen. EDC is known to be able to form an isopeptide bond between carboxyl and amine reactive groups. Surprisingly EDC did not form significant number of isopeptide bonds between intra-collagen and inter-collagen. EDC treatment enhances the helicity of the polyproline II conformation and fibril assembly. The treatment increases the hydrothermal stability, enhances cell viability and inhibit breakdown by bacterial collagenases. EDC treatment is a simple method to manufacture durable biomatrix with desirable properties. (C) 2013 Elsevier Ltd. All rights reserved.