Dual-Crosslinked Gelatin/Dextran Medical Hydrogels Based on Aldimine Condensation and Photopolymerization

Hydrogels have attracted considerable attention as biomedical materials owing to their distinctive properties; however, improvements in mechanical strength, biodegradability, and biocompatibility remain essential for advanced clinical applications. This study developed a new dual-crosslinked hydrogel based on gelatin (Gel) and dextran (Dex) via sequential aldimine condensation and photopolymerization. Natural Gel and Dex were functionalized to synthesize methacrylated Gel (GelMA) and oxidized Dex (ODex), respectively. An imine-linked network was initially formed between GelMA and ODex via aldimine condensation, followed by a second crosslinked network generated through blue-light-induced free-radical polymerization of GelMA, yielding dual-crosslinked hydrogels (GMODs). ¹H NMR and FT-IR analyses confirmed the successful functionalization and formation of dual-crosslinked structure. The dual-crosslinked network enhanced the thermal stability and water-retaining capacity of the freeze-dried hydrogels (DGMODs) while reducing the surface wettability and equilibrium swelling ratio of GMODs. The maximum compressive strength (σₘ) increased with crosslinking density; GMOD-2, with moderate crosslinking density, remained intact under 85% compressive strain and achieved σₘ of 108.0 kPa. The degradation rate of GMODs was tunable by adjusting the crosslinking density, thereby modulating their drug-release behavior. GMOD-3, possessing the highest crosslinking density, exhibited effective drug-sustained release for up to five weeks. Biological evaluations, including cytotoxicity assays, live/dead cell staining, and hemolysis tests, verified excellent cytocompatibility (cell survival rate > 92%) and minimal hemolysis ratio (<5%). Furthermore, inhibition zone tests preliminarily revealed moderate antibacterial activity for GMOD-1. The GMOD hydrogels exhibited superior compressive robustness, adjustable biodegradability, and excellent biocompatibility, holding great potential for biomedical applications such as sustained drug-delivery system.