Microporous photocrosslinked silk-tropoelastin hydrogels for tissue engineering applications

Hydrogels are widely used in tissue engineering, but conventional nanoporous hydrogel structure can restrict nutrient diffusion and hinder cell infiltration and migration. Silk fibroin (referred to as ‘silk’) hydrogels crosslinked through di-tyrosine bonds are elastomeric and compatible with modern light-based fabrication approaches, but their nanoporosity and time-dependent mechanical stiffening constrain their performance in tissue engineering and regenerative medicine applications. Here, we present a facile strategy to simultaneously enhance porosity and stabilize the mechanical properties of silk hydrogels by incorporating tropoelastin and photocrosslinking native tyrosine residues in both proteins without chemical modification. The addition of tropoelastin induced the formation of tunable nano- to microscale particles through hydrophobic and electrostatic interactions, modulating globule coalescence and enabling controlled porous network formation. Hybrid hydrogels prepared by combining silk and tropoelastin at equal weight concentrations exhibited markedly reduced mechanical stiffening and enhanced cellular infiltration and migration in vitro and in vivo relative to silk-only hydrogels, attributable to their unique microporous structure. Following subcutaneous implantation in mice, hybrid hydrogels showed reduced fibrous encapsulation compared to silk-only formulations, while avoiding the rapid degradation observed in tropoelastin-only systems. In addition, the photocrosslinked hybrids effectively sealed ex vivo wound models and supported high-fidelity patterning for advanced light-based biofabrication. This work demonstrates how leveraging intermolecular protein interactions provides a versatile materials-engineering platform for tailoring hydrogel structure and mechanical stability.