Thiol-Thioester Exchange Reactions in Precursors Enable pH-Triggered Hydrogel Formation

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Regenerative Medicine

Background:

• * Bio-interactive hydrogel formation requires responsiveness to physiological stimuli.
• * Current methods for in situ hydrogel formation often lack precise control over activation.
• * Targeted delivery and localized action are crucial for effective tissue regeneration therapies.

Purpose of the Study:

• * To develop a pH-controlled in situ hydrogel formation system using latent cross-linkers.
• * To investigate the mechanism of pH-sensitive thiol-thioester exchange reactions for hydrogel network formation.
• * To explore the potential of these hydrogels in tissue regeneration, particularly for inflamed tissues.

Main Methods:

• * Synthesis of thiopeptolide/thio-depsipeptide derivatives as pH-sensitive cross-linkers.
• * Characterization of pH-triggered thiol-thioester exchange reactions.
• * Polymerization of α,ω-dithiols with maleimide-functionalized multi-arm polyethylene glycol to form hydrogel networks.

Main Results:

• * Thiopeptolide/thio-depsipeptides demonstrated pH-sensitive thiol-thioester exchange, generating reactive α,ω-dithiols.
• * The generated dithiols successfully reacted with maleimide-functionalized polyethylene glycol to form hydrogel networks.
• * The water solubility and diffusibility of the peptide mimetics facilitate localized hydrogel formation.

Conclusions:

• * pH-controlled in situ hydrogel formation is achievable using latent cross-linkers that act as sensors.
• * Thiol/thioester-containing peptide mimetics are effective sensory precursors for localized hydrogel formation.
• * These hydrogels hold promise for applications in tissue regeneration, including the treatment of inflamed urinary tract tissues.