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It has been demonstrated that peptides, containing sequences for integrin binding, can up-regulate cell binding and adhesion, especially if they have a native conformation, like cyclic RGD.80 By reintroducing the integrin ligand GFOGER into an EDC cross-linked scaffold, a recent study showed significant improvement in cell attachment and spreading for several cell types, Fig. This strategy has been shown to be able to control migration of cells independently of the total number of cross-linkers.119 However, as an emerging field of tailored cross-linking, there remains many avenues of exploration for peptide cross-linkers.120 All of the methods above react in ways which do not eliminate vital ligands for cell culture and proliferation, while still creating mechanically stable scaffolds. After reacting copper with the collagen, the network had enhanced protease resistance without changing the structure.117 Another tack is to use self cross-linking systems.18,118 In the case of collagen and chitosan, blends can achieve the same stability through internal chemical reactions as they can through the use of chemical cross-linkers.18 Finally, cross-linking via peptides is another route, allowing different functionality to be built in, including ligands for collagenase (MMP sequences). It has been shown, for example, that cross-linkers which interfere with integrin ligands cause significant decreases in cell attachment, proliferation and migration.98,109–111 In general, as the cross-linking strength increases, the cellular response becomes less favorable, even in the absence of cytotoxic effects due to the cross-linker itself. 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