Linker-Regulated H₂S Release from Aromatic Peptide Amphiphile Hydrogels

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Chemical Engineering

Background:

• Hydrogen sulfide (H2S) delivery requires controlled release due to its reactivity, short biological half-life, and potential toxicity.
• Hydrogels offer a promising platform for localized H2S delivery.
• Aromatic peptide amphiphiles (APAs) can form hydrogels with tunable mechanical properties.

Purpose of the Study:

• To develop APA-based hydrogels capable of controlled hydrogen sulfide (H2S) release.
• To investigate the impact of linker structure within APAs on H2S release kinetics.
• To correlate hydrogel mechanical properties with H2S release rates.

Main Methods:

• Synthesis of APAs incorporating an S-aroylthiooxime (SATO) H2S donor and varying linker units.
• Characterization of APA self-assembly, hydrogelation, and mechanical properties using TEM, CD spectroscopy, and rheology.
• Quantification of H2S release triggered by cysteine (Cys) using electrochemical and fluorescent probes in cardiomyocyte models.

Main Results:

• APA hydrogels were successfully formed with tunable mechanical properties.
• H2S release rates were modulated by the linker structure and hydrogel stiffness.
• Slower H2S release correlated with increased gel stiffness and slower cysteine penetration.

Conclusions:

• APA hydrogels provide a versatile platform for controlled local delivery of hydrogen sulfide.
• Hydrogel mechanical properties, influenced by linker design, are critical for regulating H2S release kinetics.
• This approach holds potential for therapeutic applications requiring precise H2S administration.