Injectable thiol-yne-crosslinked γ-PGA/alginate hydrogels with chlorogenic acid-loaded nanoparticles for
Jianian Wang1, Yanbin Bao1, Shuqi Zhang1
1State Key Laboratory of Bio-based Fiber Materials, Tianjin University of Science and Technology, Tianjin 300457, China; Key Laboratory of Industrial Fermentation Microbiology, Tianjin University of Science and Technology, Ministry of Education, Tianjin 300457, China; Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, School of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
Abstract:
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.
