Injectable Fullerenol/Alginate Hydrogel for Suppression of Oxidative Stress Damage in Brown Adipose-Derived Stem Cells and Cardiac Repair

Stem cell implantation strategy has exhibited potential to treat the myocardial infarction (MI), however, the low retention and survival limit their applications due to the reactive oxygen species (ROS) microenvironment after MI. In this study, the fullerenol nanoparticles are introduced into alginate hydrogel to create an injectable cell delivery vehicle with antioxidant activity. Results suggest that the prepared hydrogels exhibit excellent injectable and mechanical strength. In addition, the fullerenol/alginate hydrogel can effectively scavenge the superoxide anion and hydroxyl radicals. Based on these results, the biological behaviors of brown adipose-derived stem cells (BADSCs) seeded in fullerenol/alginate hydrogel were investigated in the presence of H2O2. Results suggest that the fullerenol/alginate hydrogels have no cytotoxicity effects on BADSCs. Moreover, they can suppress the oxidative stress damage of BADSCs and improve their survival capacity under ROS microenvironment via activating the ERK and p38 pathways while inhibiting JNK pathway. Further, the addition of fullerenol can improve the cardiomyogenic differentiation of BADSCs even under ROS microenvironment. To assess its therapeutic effects in vivo, the fullerenol/alginate hydrogel loaded with BADSCs were implanted in the MI area in rats. Results suggest that the fullerenol/alginate hydrogel can effectively decrease ROS level in MI zone, improve the retention and survival of implanted BADSCs, and induce angiogenesis, which in turn promote cardiac functional recovery. Therefore, the fullerenol/alginate hydrogel can act as injectable cell delivery vehicles for cardiac repair.