Linker-Regulated HS Release from Aromatic Peptide Amphiphile Hydrogels.

Controlled release is an essential requirement for delivery of hydrogen sulfide (HS) because of its reactive nature, short half-life in biological fluids, and toxicity at high concentrations. In this context, HS delivery via hydrogels may be beneficial as they can deliver HS locally at the site of interest. Herein, we employed hydrogels based on aromatic peptide amphiphiles (APAs) with tunable mechanical properties to modulate the rates of HS release. The APAs contained an aromatic -aroylthiooxime (SATO) HS donor attached with a linker to a short IAVEEE hexapeptide. Linker units included carbonyl, substituted -methylenes, alkenyl, and alkyl segments with the goal of evaluating the role of linker structure on self-assembly, capacity for hydrogelation, and HS release rate. We studied each peptide by transmission electron microscopy, circular dichroism spectroscopy, and rheology, and we measured HS release rates from each gel, triggering SATO decomposition and release of HS by addition of cysteine (Cys). Using an HS-selective electrode probe as well as a turn-on fluorescent HS probe in the presence of H9C2 cardiomyocytes, we found that the rate of HS release from the hydrogels depended on the rate of Cys penetration into the nanofiber core with stiffer gels showing longer overall release.