Engineering Dynamic Hydrogels via GelMa-AlgMa Hybrids for Enhanced Swelling, Porosity, and Tissue Mimicry

Hydrogels have gained prominence in biomedical applications, including drug design, tissue engineering, and wound dressing, due to their versatile properties. In this study, we investigated the mechanical and biological properties of a photo-cross-linked hydrogel hybrid composed of methacrylated gelatin (GelMa) and methacrylated alginate (AlgMa). Leveraging the stable, cell-adhesive properties and delayed erosion of GelMa alongside the swelling behavior and negative charge of AlgMa, we developed a hybrid hydrogel that mimics native tissue mechanics and provides tailored viscoelastic properties with controlled remodeling. Rheological analysis revealed concentration-dependent changes in storage and loss moduli. GelMa exhibited a low loss modulus favorable for cell motility, while AlgMa demonstrated rapid swelling and increased stability modulus, emulating physiological tissue mechanics. Swelling and strain tests highlighted the dynamic remodeling capacity of the composite, with the 1:3 L-AlgGelMa hybrid exhibiting significant swelling. AlgMa acted as a sacrificial element, while the hybrid maintained mechanical properties conducive to cell attachment and migration over 21 days. Scanning electron microscopy revealed increased pore sizes due to swelling, enhancing infiltration. Cell viability assays demonstrated that L-GelMa exhibited significantly higher viability than collagen controls by day 14, while the 1:3 L-AlgGelMa Hybrid showed delayed but sustained cell proliferation with diminished fibronectin deposition and enhanced cell infiltration, confirming that AlgMa's erosion creates a diminished need for ECM remodeling and transient porosity, facilitating migration. Additionally, the hydrogel's tunable electrostatic environment, driven by AlgMa's charge, suggests potential for improved growth factor retention and signaling. These findings demonstrate that the AlgGelMa hybrid hydrogel provides a bioactive, mechanically adaptable platform, combining structural integrity with dynamic remodeling for regenerative applications.