Biopolymer-Based Hydrogel Beads with Enhanced Stability and pH/Ion-Responsive Controlled Release through a Dual-Cross-Linking Strategy

The composite biopolymer hydrogel beads (G-SA-cCNF) based on gelatin (G)/sodium alginate (SA)/carboxylated cellulose nanofibrils (cCNF) were prepared by a dual-cross-linking method using transglutaminase (TG) and calcium chloride (CaCl₂) as cross-linking agents. Effects of TG cross-linking time on the structure, swelling response, and controlled-release behaviors of hydrogel beads were mainly evaluated. TG cross-linking improved the sphericity, water-holding capacity, texture, mechanical properties, and thermal stability of hydrogel beads. The hydrogel beads exhibited remarkable pH/ion-responsive characteristics. In simulated gastric fluid, the diameter decreased that can provide protection for active substances, while in simulated intestinal fluid, the diameter increased that can facilitate the controlled release of active substances. TG cross-linking can endow the hydrogel beads with a denser internal network structure, effectively controlling the release of bioactive substances such as bovine serum albumin (BSA). Overall, TG cross-linking improved the properties of the hydrogel beads and enabled precise regulation of release.