Peptide hydrogel with self-healing and redox-responsive properties

Abstract

We have rationally designed a peptide that assembles into a redox-responsive, antimicrobial metallohydrogel. The resulting self-healing material can be rapidly reduced by ascorbate under physiological conditions and demonstrates a remarkable 160-fold change in hydrogel stiffness upon reduction. We provide a computational model of the hydrogel, explaining why position of nitrogen in non-natural amino acid pyridyl-alanine results in drastically different gelation properties of peptides with metal ions. Given its antimicrobial and rheological properties, the newly designed hydrogel can be used for removable wound dressing application, addressing a major unmet need in clinical care.

Modulation of hydrogel networks by metal ions

“…A short peptide named F9 4′PyA (pyridyl‐alanine) (Ac‐4′PyA‐FRFRFRF‐4′PyA‐CONH 2 ) produced a redox‐responsive metallogel only in the presence of Cu 2+ ions, while the presence of Cu + did not provide any gel. The hydrogel with Cu 2+ revealed to be self‐healing indeed, after applying strain it was able to recover its storage modulus ensuring its injectability; conversely, the reduction of Cu 2+ to Cu + with ascorbate, changed the stiffness of the gel and led to its complete dissolution 69 …”

“…conversely, the reduction of Cu 2+ to Cu + with ascorbate, changed the stiffness of the gel and led to its complete dissolution. 69 Also ferrocene (FcH), that is, an organometallic complex consisting of two cyclopentadienyl ligands coordinated to a central Fe 2+ ion, 81 is often employed as redox trigger in peptide hydrogels. 82 Its oxidation can be achieved by the addition of a Fe 3+ salt that causes the loss of the supramolecular association: Indeed, ferrocene is a hydrophobic and neutral molecule that, if oxidized, becomes ferrocenium, that is, ionic nature, and loses coordination properties.…”

Self-Healing Hydrogels: From Synthesis to Multiple Applications

“…For example, peptide F9 and 4′-pyridyl-alanine could form a redox antibacterial self-healing hydrogel in the presence of Cu(II) ions. 95 Cu(II) had good redox properties and the coordination of Cu(II) with 4′-pyridylalanine produced a good self-healing property. A reduction process could be performed with the help of ascorbate, leading to the decrease of the self-healing property.…”

Peptide hydrogels: Synthesis, properties, and applications in food science

“…In the study of D'Souza et al. (2022), metal ions were used to assemble hydrogels through metal complex formation, a strategy for creating self‐healing materials. To facilitate cross‐linking they have introduced pyridyl‐alanine residues (3'PyA and 4'PyA) at both termini of 9‐residue peptides (Figure 2a).…”

“…(b) transmission electron microscopy (TEM) image showing the fibrils of the hydrogel formed from F9 4ʹPyA (1 wt %) and Cu(II) (1 Equiv) in buffer. (c) A hydrogel formed from F9 4ʹPyA and Cu(II) dissolves after 5 min when ascorbate is added; (d) EPR spectra acquired at room temperature of the hydrogel formed by F9 4ʹPyA and 1 Equiv Cu(II) (D'Souza et al., 2022).…”