Injectable thiol-yne-crosslinked γ-PGA/alginate hydrogels with chlorogenic acid-loaded nanoparticles for antibacterial and antioxidant activity.

Injectable hydrogels capable of addressing both bacterial contamination and oxidative stress are attractive for local biomedical applications, yet integrating controllable network formation with sustained bioactivity remains challenging. Herein, an injectable γ-poly(glutamic acid)/alginate (γ-PGA/Alg) hydrogel was constructed via thiol-yne photoclick crosslinking between alkynylated γ-PGA and thiolated alginate, and further functionalized with chlorogenic acid-loaded chitooligosaccharide/tripolyphosphate nanoparticles (NP-CA). The hydrogel contained ∼98 wt% water and formed a dual crosslinked network comprising stable thioether linkages and dynamic disulfide bonds, whose respective roles in structural integrity and recovery behavior were clarified by reduction experiments. NP-CA exhibited an average hydrodynamic diameter of 239.9 nm, an encapsulation efficiency of 85.9%, and a loading content of 5.35%. The incorporation of NP-CA decreased the equilibrium swelling ratio, improved water retention, and reduced mass loss during degradation. Zeta potential, FT-IR, and microstructural analyses suggest that NP-CA is integrated into the hydrogel network through electrostatic interactions, hydrogen bonding, and physical confinement. In addition, the system exhibited a sustained release behavior of CA, with the release rate decreasing as nanoparticle loading increased. The hydrogels showed shear-thinning behavior and rapid modulus recovery under cyclic strain. NP-CA loading enhanced radical-scavenging activity, with the highest-loading group reaching 89.81 ± 2.74% for DPPH and 92.52 ± 3.23% for ABTS⁺ scavenging. NP-CA-loaded hydrogels inhibited both Escherichia coli and Staphylococcus aureus, while control experiments indicated that blank nanoparticles did not significantly contribute under the present conditions. All formulations showed hemolysis below 1% and no evident cytotoxicity toward L929 fibroblasts. These results indicate that thiol-yne-crosslinked γ-PGA/Alg hydrogels combined with nanoparticle incorporation provide a practical approach for constructing multifunctional injectable biomaterials with sustained bioactivity.