Hierarchically constructed a noncovalent chitosan/hyaluronic acid hydrogel with entanglement-enhanced toughness

Hydrogel-based artificial skin (HAS), resembling natural skin, has widespread applications. Noncovalent natural polymer-based hydrogel (NNH) with desirable biocompatibility and fast biodegradability represents an ideal candidate for HAS. However, the low toughness limited the practical applications of NNH, and presently, no effective approach has been found to boost NNH toughness without compromising biocompatibility and biodegradability. Here we propose a hierarchical strategy of standing layering (S-layering), water washing rearranging (WW-rearranging), and host-guest osmotic crosslink (HG-crosslink) to create a noncovalent chitosan (CS)/hyaluronic acid (HA) hydrogel with strong toughness. The combined use of S-layering and WW-rearranging formed a rigid honeycomb-like architecture (block) of CS/HA hydrogel, providing a regular structural foundation for HG-crosslink between the flexible adhesives and the blocks to form numerous flexible entanglement domains, achieving a toughness of 570 kJ/m³, 7-fold that of physically crosslinked HA/CS hydrogels. This strategy fabricated NNH using purely natural polymers, fulfilling the mechanical and biocompatibility requirements for HAS.