Light-Triggered Programmable Hydrogels Based on Natto Poly(γ-Glutamic Acid) with Tunable Adhesion and Integrated...

Protein-based hydrogels have been constrained by modest mechanics and limited responsiveness. In this study, a light-triggered, disulfide-cross-linked hydrogel based on poly(γ-glutamic acid) (γ-PGA) was established by integrating thiolated γ-PGA and α-lipoic acid (LA)-grafted γ-PGA under 405 nm irradiation. Dynamic disulfide chemistry enabled rapid gelation at a critical concentration of ≥7%, with complete gelation at a polymer concentration of 8%, a storage modulus of approximately 100 Pa, and gelation time below 60 s at 0.25% LAP. The hydrogel adhered to diverse substrates, underwent redox-triggered disassembly within 5 min in the presence of β-mercaptoethanol (βME), and maintained integrity in simulated gastric fluid (pH = 2) with about 18% mass loss after 2 h. Broad-spectrum antioxidant activity was observed, including disappearance of the 1,1-diphenyl-2-picryl-hydrazyl peak at 517 nm at 4 mg/mL and approximately 80% scavenging of hydroxyl radicals. Cytocompatibility was supported up to 640 μg/mL. In lipopolysaccharide (LPS)-stimulated macrophages, pretreatment reduced reactive oxygen species (ROS) and nitric oxide (NO), preserved mitochondrial membrane potential (ΔΨm), and shifted gene expression toward an anti-inflammatory profile. These findings indicated that dynamic disulfide chemistry endowed the γ-PGA platform with programmable gelation, reversible adhesion, gastric stability, and coupled antioxidant and anti-inflammatory activities relevant to food-related oral delivery.