A Mechanical Robust Tunable Terepthaloyl Modified Chitosan Hydrogel Matrix for Modulating Biological Response

ABSTRACT The remarkable antibacterial properties of chitosan, coupled with the biocompatibility of its hydrogel forms, present significant opportunities for innovations in tissue engineering. In this study, we developed a novel crosslinked chitosan hydrogel through a chemical reaction between chitosan and terepthaloyl chloride at varying concentrations (0.25, 0.5, 0.75, and 1 mmol). When comparing the pure chitosan (CS) to the terepthaloyl chloride crosslinked chitosan (TPC‐CS), the resulting hydrogel exhibited a significantly enhanced antibacterial effect against common pathogens, such as Escherichia coli and Staphylococcus aureus . Notably, the formulation TPC‐CS4, formed with a concentration of 1 mmol, was particularly effective in promoting the proliferation of epithelial cells while also stimulating the expression of vascular endothelial growth factor. This expression is crucial as it supports increased angiogenic activity, which is vital for tissue regeneration. Furthermore, the TPC‐CS4 hydrogel demonstrated excellent biocompatibility, as verified through cytotoxicity experiments conducted on fibroblast cells, indicating its safety for use in biological environments. This research illustrates that the chemical crosslinking of chitosan hydrogels not only enhances the structural integrity of the material but also significantly boosts cell proliferation and angiogenic capabilities. Therefore, terepthaloyl chloride‐based chitosan hydrogels emerge as promising candidates for various applications in the field of tissue engineering.