Peptide-based supramolecular hydrogels have been tested in regenerative medicine as a mechanical, morphological and biofunctional mimic of the proteins that compose the extracellular matrix
(ECM). As an example, minimalistic fmoc-containing amphiphilic peptide sequences (of 2 aminoacids) are able to generate supramolecular nanofiber assemblies that further cross-link and form
supramolecular hydrogels under cell culture conditions.[1] These systems can be tailored in terms of mechanical properties and chemical composition and thus, can be tuned to promote cell
differentiation.[2,3] A main disadvantage of these systems is the presence of the aromatic fmoc-unit that is needed for the self-assembly but can induce toxicity. Recently, a series of fmoc-free short
peptide sequences (of 3 aminoacids) were identified and reported to generate supramolecular nanofibrous networks that gel near neutral pH. [4] One of these sequences is FFD, which forms
nanotapes under aqueous environment. This system gels at low pH but it is unstable at the physiological conditions. When FFD is combined with GHK (a Cu2+ specific sequence), nanotapes are
converted into nanofibers, and these are generating supramolecular hydrogels in the presence of exogenous Cu2+.[5] These gels are formed at neutral pH but are not stable over time (e.g. 1 week),
possibly due to the weak interaction between FFD and GHK tripeptides. Therefore we are testing different chemical modifications to improve the hydrogel stability under cell culture conditions over
larger timeframes. We envisage that these devices will be useful for wound healing due to the known anti-inflammatory activity of the GHK-Cu complex.
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