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Ideal hydrogels for tissue engineering applications should mimic the properties of native extracellular matrices and optimize the cell behavior. Silk fibroin (SF) that possesses tunable mechanical strength and low cytotoxicity and elastin protein that stimulates cell viability are complementary for hybrid hydrogels. Here, hydrolyzed elastin peptide (HEP) and reconstituted SF (RSF) are combined to generate hybrid hydrogels. Physical cross-links are β-sheet conformation induced by heat in SF, and chemical cross-links are induced between HEP and RSF by glutaraldehyde (GA). The influence of the hybrid ratio on the molecular structure and mechanical properties is studied in detail. Results show that with only 0·1% GA, the non-gelling multiarmed HEP could accelerate the physical gelation process of SF to result in a homogeneous dual-cross-linked structure. The β-sheet conformation increases linearly with the SF content. The hybrid hydrogels possess compressive moduli of 4–70 kPa and shear storage moduli of 0·005 to ∼40 kPa, demonstrating tunable mechanical properties to cover a stiffness spectrum for various soft-tissue applications. Cell culture results suggest little cytotoxicity of such dual-cross-linked hybrid hydrogels. The hybrid hydrogels can be used as bioinks or biocoatings for tissue engineering.

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