Abstract 331: Conjugation of Graphene Oxide With Chitosan Improves Survival of Transplanted Allogeneic Stem Cells and Preserves Ventricular Function in the Infarcted Heart

Abstract

Allogeneic mesenchymal stem cells (MSCs) derived from bone marrow are considered to ideal candidate cell type for myocardial repair after a cardiac injury. However, recent reviews of allogeneic MSCs based clinical trials reported that transplanted cells were not able to survive for long term in the heart. Therefore, strategies to improve survival of transplanted cells would preserve the benefits of allogeneic MSCs therapy for heart repair. Recently, graphene oxide (GO) based biomaterials are being widely investigated for their ability to improve survival of transplanted MSCs in the heart. However, the presence of reactive oxygen functional groups (-OH, -COOH) in the structure of GO increases oxidative stress and activate cell death pathways, which impairs the benefits of GO based biomaterials. Therefore, to improve benefits of GO for stem cell delivery, we synthesized a thermosensitive hydrogel by conjugating GO with chitosan (CS). Our fourier transformed infrared spectrum (FTIR) analysis revealed an interaction between oxygen functional groups of GO and amino (-NH2) groups of chitosan. Our data 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, CS-GO biomaterial was cyto-compatible as there was no cytotoxicity caused by CS-GO to MSCs. Furthermore, CS-GO also prevented hypoxia induced apoptosis of MSCs. We employed this novel biomaterial to deliver allogeneic MSCs to the infarcted heart in a rat model of myocardial infarction. After 5 weeks of cell transplantation, there was a significant improvement in the survival of implanted MSCs and cardiac function in CS-GO group. Therefore, conjugation of GO with chitosan prevented GO mediated ROS generation and cell death. Also, CS-GO mediated delivery of allogeneic MSCs to infarcted heart improved the survival of transplanted cells and preserved cardiac function.