Peptide-polyurea hybrids: a platform for tunable, thermally-stable, and injectable hydrogels

Drawing inspiration from natural systems, such as the highly segmented structures found in silk fibroin, is an important strategy when designing strong, yet dynamic biomaterials. Polymer-peptide hybrids aim to incorporate the benefits of hierarchical polypeptide structures into synthetic platforms that are promising materials for hydrogel systems due to aspects such as their biocompatibility and structural tunability. In this work, we demonstrated the utility of poly(ethylene glycol) (PEG) peptide-polyurea hybrids as self-assembled hydrogels. Specifically, poly(ε-carbobenzyloxy-L-lysine)-b-PEG-b-poly(ε-carbobenzyloxy-L-lysine) and poly(β-benzyl-L-aspartate)-b-PEG-b-poly(β-benzyl-L-aspartate) triblock copolymers were used as the soft segments in linear peptide-polyurea (PPU) hybrids. We systematically examined the effect of peptide secondary structure and peptide segment length on hydrogelation, microstructure, and rheological properties of our PPU hydrogels. Polymers containing α-helical secondary structures resulted in rapid gelation upon the addition of water, as driven by hierarchical assembly of the peptide segments. Peptide segment length dictated gel strength and resistance to deformation via complex relationships. Simulated injection experiments demonstrated that PPU hydrogels recover their original gel network within 10 s of cessation of high shear. Finally, we showed that PPU hydrogels remain solid-like within the range of 10 to 80 °C; however, a unique softening transition occurs at temperatures corresponding to slight melting of secondary structures. Overall, this bioinspired PPU hybrid platform provides opportunities to design synthetic, bioinspired polymers for hydrogels with tunable microstructure and mechanics for a wide range of thermal and injection-based applications.