Injectable and self-healable supramolecular hydrogels assembled by quaternised chitosan/alginate polyelectrolyte complexation for sustained drug delivery and cell encapsulation.

Hydrogels formed through phase separation during the complexation of oppositely charged polymers have unique properties, including fast self-assembly, hierarchical microstructures, and tunable properties. These features make them highly attractive materials for various biomedical applications, such as drug delivery, protective coatings, and surface adhesives. Notably, injectable polyelectrolyte complex (PEC) supramolecular hydrogels stand out for their minimally invasive administration and reduced trauma and side effects, providing attractive alternatives to covalent hydrogels, which are constrained by the irreversibility of their crosslinks, limiting their versatility and broader applicability. Sustainable marine-origin polysaccharides have been used for developing hydrogels due to their proven biocompatibility, non-cytotoxicity and wide bioavailability from renewable resources. In particular, chitosan (CHT) and alginate (ALG) have been widely employed to develop hydrogels, taking advantage of their opposite charge nature. However, the limited solubility of CHT under physiological conditions limits the range of bioapplications. Herein, we report the development of size- and shape-tunable PEC supramolecular hydrogels encompassing water-soluble quaternised CHT and ALG biopolymers, under physiological conditions, by polyelectrolyte complexation. The rheological and mechanical properties of the PECs are studied, demonstrating their injectability, self-healing behaviour, and cytocompatibility towards human adipose-derived stem cells. A sustained and controlled release of encapsulated fluorescein isothiocyanate-labelled bovine serum albumin is observed over fourteen days. This work paves the way for the design and development of advanced CHT-based injectable biomaterial platforms for a wide array of biomedical and biotechnological applications.