Ultra-Tough Hybrid Supramolecular Gelatin Hydrogels

Natural load-bearing tissues derive mechanical performance from sequential self-assembly, in which collagen fibrils first compact and are then stabilized by enzymatic covalent crosslinking. Replicating this design in synthetic hydrogels while limiting swelling and preserving toughness and viscoelasticity remains challenging. Here, we report a gelatin-based hybrid hydrogel in which tannic acid-mediated coacervation creates a compact acidic microenvironment that triggers in situ covalent crosslinking. Tannic acid induces rapid phase separation, lowers the local pH to ∼2.7, and promotes proton-catalyzed ring opening of the preloaded bis-oxazoline crosslinker, resulting in diester-linked covalent stabilization of the compacted gelatin network. This decouples physical compaction from covalent stabilization and avoids the metastability of supramolecular tannic acid-gelatin networks. The optimized formulation showed a ∼60-fold increase in storage modulus (G' ∼54 kPa) relative to acid-swollen controls and combined high extensibility (elongation at break ∼900%), tensile strength (∼2.0 MPa), and toughness (5.46 MJ m^-3). It also retained cyclic dissipation (4.21 MJ m^-3 in the first cycle) and long-term structural stability in water. In vitro, the hydrogels supported adhesion, spreading, and proliferation of human dermal fibroblasts over 3 days. Together, these results show that tannic acid-mediated compaction coupled with acid-triggered covalent crosslinking provides an effective route to strong, extensible, and dissipative gelatin hydrogels.