Tropoelastin enhances vascularization in printable protein hydrogels

This study developed a printable, protein-based hydrogel platform composed of silk fibroin and tyramine-modified gelatin and investigated whether adding recombinant human tropoelastin could improve vascularization. Gelatin was chemically modified with tyramine to enable horseradish peroxidase-mediated enzymatic crosslinking, and silk fibroin was incorporated to tune hydrogel mechanics. The authors compared SF/GT ratios of S10G90, S40G60, and S80G20 and found that higher gelatin content shortened gelation and increased elastic character, while S40G60 provided a mechanically stable hydrogel with compression modulus around 4 kPa, a range considered favourable for endothelial migration and vascular network formation. Tropoelastin did not significantly alter bulk compression mechanics at the tested concentration, but it improved fibroblast growth in selected hydrogel formulations. In 3D co-culture, GFP-HUVECs formed more elongated and sprouting structures when neonatal human dermal fibroblasts were co-encapsulated, and tropoelastin further increased the number of larger fluorescent endothelial structures. In vivo subcutaneous implantation showed cellular infiltration into both S40G60 and S40G60+TE hydrogels, thin fibrous capsules under 100 micrometres, M2-like macrophage-associated host response, and significantly enhanced blood-vessel formation around tropoelastin-containing implants at day 14. The S40G60 formulation was also adapted for extrusion-based freeform bioprinting in an alginate support bath, producing stable square and hollow cylindrical constructs while maintaining fibroblast viability and spreading. Overall, the paper demonstrates that tropoelastin can enhance early vascularization in a printable silk-gelatin hydrogel platform with soft-tissue-like mechanics.