Harnessing the mechanical properties of Gelatin methacryloyl hydrogels through cooling-induced entanglement

• Cooling-induced entanglement greatly enhances GelMA hydrogel tensile strength and Young’s modulus. • Multiscale analysis reveals reduced mesh sizes and topological entanglements as key mechanisms for mechanical reinforcement. • Visco-hyperelastic constitutive model links entanglement dynamics to time-dependent mechanical responses. • Cooling-induced entanglement enables tunable viscoelasticity for dynamic biomedical applications like tissue scaffolding. Enhancing gelatin methacryloyl (GelMA) hydrogel mechanics without compromising biocompatibility remains challenging, as conventional chemical crosslinking often disrupts degradation behavior. A cooling-induced entanglement strategy effectively improves mechanical performance while preserving biological properties; however, its underlying mechanisms remain unclear. This study demonstrates that extended cooling durations significantly enhance the mechanical properties of GelMA hydrogels. Microstructural analyses reveal cooling-induced formation of compact polymer networks with reduced mesh sizes. Molecular dynamics (MD) simulations confirm that the cooling process promotes topological entanglements that govern mechanical reinforcement. Guided by these insights, we propose a theoretical model to predict the stress responses of GelMA hydrogels under various cooling durations, establishing quantitative correlations between entanglement mechanisms and mechanical outcomes. This study provides a fundamental understanding of the interplay between cooling conditions, microstructure, and mechanical performance, offering a robust framework for designing GelMA hydrogels with optimized mechanical properties for advanced biomedical applications.