Chitosan-based hydrogels for nitric oxide-mediated myocardial repair: advances and prospects

Myocardial infarction (MI) is a leading cause of morbidity and mortality across the world, and thus, there is a need to develop new therapeutic modalities for cardiac treatment. Recent studies have highlighted the ability of chitosan-based hydrogel to release nitric oxide (NO) in a sustained manner over a duration of days to weeks. This type of delivery significantly boosts angiogenic networks, reduces the size of the infarct, and improves the function of the left ventricle compared with conventional methods of NO administration. A range of NO releasing species, such as diazeniumdiolates and S-nitrosothiols, have been integrated into chitosan scaffolds to induce localized and temporally controlled NO bioavailability, thus overcoming the short half-life and systemic toxicity inherent to free NO donors. The current review evaluates the recent advances in the design, efficiency, and therapeutic potential of chitosan-based NO-releasing hydrogel, especially in the results of preclinical MI models. The main issues of mechanical strength, degradation kinetics, and in vivo stability, as well as new approaches based on hybrid biomaterials and stimuli-responsive platforms, are discussed. The shortcomings of these hydrogels and future opportunities for enhancing their translational opportunities in cardiovascular therapeutics are outlined in detail.