Crosslinking Agents in the Targeted Design of Chitosan-Based Materials

This review summarizes the data on the mechanisms and features of the application of commercially available crosslinking agents, such as aldehydes (glutaraldehyde, genipin, and aromatic monoaldehydes) and diglycidyl ethers, for the production of chitosan-based materials. It is shown that the choice of a crosslinking agent and a method and conditions (pH, temperature, nature of an acid in a chitosan solution) enables one to targetedly control the morphology, physicochemical properties, swelling, degradation kinetics, and biocompatibility of the resulting hydrogels, films, and porous materials. The development of crosslinking strategies, including the formation of dynamic covalent bonds and the use of macromolecular crosslinking agents, opens up the prospects for the production of injectable, self-healing, and stimulus-responsive systems for biomedical applications. Special attention is focused on the solution of the problem concerning the cytotoxicity of traditional crosslinking agents by using less toxic alternatives (genipin and diglycidyl ethers) and the methods that reduce the degree of crosslinking without significant deteriorating the mechanical properties of the materials.