A chitosan-glutathione based injectable hydrogel for suppression of oxidative stress damage in cardiomyocytes

Overproduction of reactive oxygen species (ROS) is closely associated with myocardial infarction. The oxidative stress damage caused by ROS in grafted cells and host cells presents a major obstacle for successful myocardial repairs in cardiac tissue engineering. Previous injectable biomaterials in use of myocardial repairs typically lack consideration of their antioxidant properties. In this work, a thermosensitive chitosan chloride-glutathione (CSCl-GSH) hydrogel was developed to suppress the oxidative stress injury in cardiomyocytes (CMs). Glutathione (GSH) was conjugated on the chitosan chloride (CSCl) chain via amide bonds between carboxylic acid moieties of GSH and amine groups of CSCl. Our data show that CSCl-GSH conjugates in vitro could effectively scavenge the superoxide anion, hydroxyl radical and DPPH radical even at high concentrations and its antioxidant capacity can be modulated via adjusting the grafted degree of CSCl-GSH conjugates. In addition, CSCl-GSH hydrogels have shown an excellent biocompatibility to support the adhesion and survival of CMs. Moreover, it can remove the excessive intracellular ROS and thus suppress the oxidative stress damage and apoptosis in CMs in the presence of high ROS. These results suggest CSCl-GSH hydrogels could effectively support the myocardial repair via attenuating the oxidative stress damage to cells.