The objective of this study was to develop an
injectable and biocompatible
hydrogel which can efficiently deliver a nanocomplex of
graphene oxide (GO) and
vascular endothelial growth factor-165 (
VEGF) pro-angiogenic gene for myocardial
therapy. For the study, an efficient nonviral gene delivery system using
polyethylenimine (PEI) functionalized GO nanosheets (fGO) complexed with DNAVEGF was formulated and incorporated in the low-modulus methacrylated
gelatin (GelMA)
hydrogel to promote controlled and localized gene therapy. It was hypothesized that the fGOVEGF/GelMA
nanocomposite hydrogels can efficiently transfect myocardial tissues and induce favorable
therapeutic effects without invoking cytotoxic effects. To evaluate this hypothesis, a rat model with acute
myocardial infarction was used, and the therapeutic
hydrogels were injected intramyocardially in the peri-
infarct regions. The secreted
VEGF from in vitro transfected cardiomyocytes demonstrated profound mitotic activities on endothelial cells. A significant increase in myocardial capillary density at the injected peri-
infarct region and reduction in
scar area were noted in the infarcted hearts with fGOVEGF/GelMA treatment compared to infarcted hearts treated with untreated
sham, GelMA and DNAVEGF/GelMA groups. Furthermore, the fGOVEGF/GelMA group showed significantly higher (p < 0.05, n = 7) cardiac performance in echocardiography compared to other groups, 14 days postinjection. In addition, no significant differences were noticed between GO/GelMA and non-GO groups in the serum
cytokine levels and quantitative PCR based inflammatory
microRNA (
miRNA) marker expressions at the injected sites. Collectively, the current findings suggest the feasibility of a combined
hydrogel-based gene therapy system for
ischemic heart diseases using nonviral hybrid complex of fGO and
DNA.