Abstract 24: Graphene Oxide Containing Thermosensitive Hydrogel Improves the Survival of Transplanted Stem Cells in Ischemic Myocardium

Abstract

Bone marrow derived mesenchymal stem cell (MSC) therapy has the potential to preserve cardiac function and prevent heart failure following a myocardial infarction (MI). However, in our recent studies, long term survival of transplanted stem cells was not detected, which was associated with deterioration of cardiac function. Therefore, strategies to enhance survival of transplanted cells would preserve the benefits of MSCs therapy for heart repair. Recently, graphene oxide (GO) nanosheets are being widely investigated for their ability to promote adherence and homing of transplanted MSCs to the extra cellular matrix in the heart. However, the presence of reactive oxygen functional groups (-OH, -COOH) in the structure of GO increases oxidative stress and activate apoptotic pathways in MSCs, which impairs the benefits of GO based biomaterials. Therefore, to nullify these side effects of GO, we synthesized a novel thermosensitive hydrogel by conjugating GO with chitosan (CS). Our Fourier transformed infrared spectrum (FTIR) analysis revealed an interaction between the oxygen functional groups of GO and amino (-NH2) groups of chitosan. Our data also demonstrate that CS masked the reactive functional groups of GO and prevented GO mediated ROS induction. This novel chitosan-graphene oxide (CS-GO) composite exhibited optimal porosity for cell conjugation and retention. Furthermore, this novel biomaterial was cyto-compatible as it exerted negligible toxicity to encapsulated MSCs. Upon exposure to hypoxic/ischemic environment, we observed a significant increase in apoptosis in MSCs as evidenced by an increase in the Bax/Bcl-xl ratio and caspase 3 activation. However, conjugation of MSCs to CS-GO polymer prevented hypoxia induced apoptosis. Therefore, coupling of GO with chitosan prevented GO mediated oxidative stress and downregulated hypoxia induced apoptosis of MSCs. Therefore, the outcome of this study will provide a novel delivery system for MSCs to the heart and improve their long term survival in the infarcted heart.