Dual Cross-Linking of Catechol-Alginate Hydrogels: A Strategy for Enhanced Stability and Sustained Drug Delivery

This study presents the development and characterization of a novel catechol-conjugated alginate (C-Alg) hydrogel system that combines Ca²⁺-mediated ionic cross-linking with laccase-catalyzed enzymatic cross-linking. While traditional Ca²⁺-mediated alginate hydrogels are known for their rapid gelation, they suffer from poor long-term stability in physiological conditions, limiting their effectiveness in medical applications. In the system developed here, the hydrogel initially formed upon mixing C-Alg with Ca²⁺, followed by gradual chemical catechol cross-linking through enzyme catalysis. The C-Alg hydrogels exhibited markedly improved mechanical strength and enhanced stability compared to those cross-linked with Ca²⁺ alone. This dual cross-linking approach also effectively slowed the release rates of model molecules with molecular weights ranging from several hundred to ten thousand. These advantages highlight the potential of C-Alg hydrogels as effective platforms for injectable drug delivery systems.