This review systematizes data on the mechanisms and features of using commercially available crosslinking agents — aldehydes (glutaraldehyde, genipin, aromatic monoaldehydes) and diglycidyl ethers — for the fabrication of chitosan- based materials. It is demonstrated that the choice of crosslinking agent, method, and conditions (pH, temperature, nature of the acid in the chitosan solution) enables a targeted control over the morphology, physicochemical properties, swelling and degradation kinetics, as well as the biocompatibility of the resulting hydrogels, films, and porous materials. The development of crosslinking strategies, including formations of dynamic covalent bonds and usage of macromolecular crosslinking agents, opens prospects for fabrication of injectable, self- healing, and stimulus- responsive systems for biomedical applications. Special attention is given to the cytotoxicity of traditional crosslinking agents through the use of less toxic alternatives (genipin, diglycidyl ethers) and methods that reduce the degree of crosslinking without significantly compromising the mechanical properties of the materials.
Kildeeva et al. (Wed,) studied this question.