pH-Triggered Coassembly of Cello-oligosaccharides and Hyaluronic Acid into Hydrogels

Polysaccharides are valuable building blocks for constructing functional hydrogel materials for diverse applications. Although many polysaccharides with high water solubility require cross-linking to be formulated into hydrogels, physically cross-linking ionic polysaccharides with biocompatible substances under mild aqueous conditions remains a significant challenge. Herein, we report the physical cross-linking of hyaluronic acid with crystalline cello-oligosaccharides via bottom-up coassembly at the molecular level. Neutralization of alkaline mixtures of cello-oligosaccharides and hyaluronate resulted in the facile preparation of translucent hydrogels with equilibrium moduli of 1-10 Pa. Structural analyses suggested that hyaluronate formed the backbone of the gel networks, while crystalline cello-oligosaccharides acted as physical cross-linkers. In vitro cytotoxicity assays demonstrated the excellent cytocompatibility of the coassembled hydrogels. Furthermore, the cationic antibiotic polymyxin B was successfully incorporated into the hydrogels, yielding antibacterial composite hydrogels. This study provides a promising strategy for the development of advanced polysaccharide-based biomaterials through physical cross-linking with crystalline oligosaccharides.