Gelatin Hydrogel Crosslinking: From Molecular Design to Functional Soft Materials

Abstract

Gelatin hydrogels combine biological origin, biodegradability, abundant chemical functionality, and broad processability, but their native thermoreversible physical networks generally lack the stability required for sustained operation. Crosslinking overcomes this limitation while regulating hydration, mechanics, transport, degradation, and responsiveness. This review examines gelatin hydrogel crosslinking from a structure–property–function perspective, connecting molecular design with physicochemical characterization and functional performance. Temperature-induced gelation and ion-mediated physical interactions are compared with small-molecule- and coupling-agent-mediated, enzyme-catalyzed, and photoinduced covalent crosslinking strategies, highlighting their different balances among reversibility, stability, processability, and biocompatibility. Particular attention is given to the characterization methods required to relate junction chemistry and network organization to swelling, thermal behavior, mechanical response, degradation, and molecular or ionic transport. These relationships are evaluated across drug delivery and controlled release, tissue engineering and wound healing, food packaging, preservation and delivery, water remediation and environmental management, wearable sensing and bioelectronics, and energy storage. Across these fields, the central challenge is not to maximize crosslinking, but to balance network stability with the molecular mobility required for function. By integrating complementary crosslinking mechanisms with multiscale characterization, gelatin can be engineered as a programmable platform for advanced soft materials.