In Situ Forming and Reversibly Cross-Linkable Hydrogels Based on Copolypept(o)ides and Polysaccharides

The emerging tide of hydrogels in biomedical fields drives them to possess good biocompatibility, tunable mechanical properties, and fast gelation process. Herein, a composite hydrogel containing copolypept(o)ides and functional polysaccharides was constructed through dynamic acylhydrazone linkages. First, a series of peptide–peptoid copolymers were synthesized by ring-opening polymerization of sarcosine (Sar) and l-glutamic acid γ-benzyl ester (BLG) N-carboxyanhydrides (NCAs). The benzyl groups of BLG units were substituted with hydrazide groups through ester–amide exchange aminolysis reaction. The statistical copolymer of poly(sarcosine-co-glutamate-hydrazide) (P(Sar-co-GH)) was chosen as an optimized precursor due to its excellent water solubility and gel-forming ability with aldehyde-modified sodium alginate (OSA). Moreover, cellulose nanocrystals (CNCs) were prepared as nanofillers to reinforce the P(Sar-co-GH)-OSA hydrogel. We demonstrated that the copolymer sequences and composition contents made a difference to the properties of the formed hydrogels by variation of the cross-linking density. The dynamic acylhydrazone bonds endowed hydrogels with pH responsiveness and reversible networks. The NIH/3T3 cells encapsulated in the hydrogels maintained high viability and proliferation abilities, indicating that the nanocomposite hydrogels could be explored to fabricate a customized responsive drug delivery system or cell scaffolds for tissue engineering.