A Reloadable Self-Healing Hydrogel Enabling Diffusive Transport of C-Dots Across Gel-Gel Interface for Scavenging Reactive Oxygen Species.

While reloadable drug delivery platforms are highly prized for the treatment of a broad spectrum of diseases, the gel-gel interface between hydrogels hinders the intergel diffusive transport of drugs and thus limits the application of hydrogels as reloadable depots. Here, this study reports the circumvention of this barrier by employing a self-healing hydrogel prepared from N-carboxyethyl chitosan and sodium alginate dialdehyde, which are cross-linked via a reversible Schiff base linkage. The injectable and bioadhesive hydrogel shows a rapid gelation time of 47 s. The dynamic self-healing process enables the efficient diffusive transport of carbon quantum dots (C-dots) into an adjacent hydrogel, and thus, the C-dots can be used to scavenge reactive oxygen species from a remote inflammation site. Specifically, the diffusive transport of the C-dots in the self-healing hydrogel after three sequential reloading steps is sevenfold greater than that in the non-self-healing counterpart. In vivo, hematoxylin and eosin staining of the murine skin at the injection site shows no apparent symptoms of inflammation in the group treated with the reloadable self-healing hydrogel. The current strategy represents a promising and straightforward route for the design of a reloadable drug delivery system for future use in clinical application.