Schematic collagen cross-linking reactions for the employed reagents. (a) Glutaraldehyde covalently binds to amino groups, but can also bind to other glutaraldehyde molecules. (b) 1-Ethyl-3-diaminopropyl-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) catalyses covalent bindings between carboxylic acid and amino groups; thus, cross-linking between collagen structures is possible. Furthermore, other extracellular matrix components containing carboxyl groups, such as glycosaminoglycans, can also be cross-linked. (c) Genipin reacts in a similar manner as glutaraldehyde, but can only bind to one other genipin molecule. (d) Transglutaminase is a highly specific enzyme catalysing collagen cross-linking between lysine and glutamine in collagen structures with the release of ammonia.