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 DNA_VEGF was formulated and incorporated in the low-modulus methacrylated gelatin (GelMA) hydrogel to promote controlled and localized gene therapy. It was hypothesized that the fGO_VEGF/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 fGO_VEGF/GelMA treatment compared to infarcted hearts treated with untreated sham, GelMA and DNA_VEGF/GelMA groups. Furthermore, the fGO_VEGF/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.

Tissue engineering (TE) is an interdisciplinary field integrating engineering, material science and medical biology that aims to develop biological substitutes to repair, replace, retain, or enhance tissue and organ-level functions. Current TE methods face obstacles including a lack of appropriate biomaterials, ineffective cell growth and a lack of techniques for capturing appropriate physiological architectures as well as unstable and insufficient production of growth factors to stimulate cell communication and proper response. In addition, the inability to control cellular functions and their various properties (biological, mechanical, electrochemical and others) and issues of biomolecular detection and biosensors, all add to the current limitations in this field. Nanoparticles are at the forefront of nanotechnology and their distinctive size-dependent properties have shown promise in overcoming many of the obstacles faced by TE today. Despite tremendous progress in the use of nanoparticles over the last 2 decades, the full potential of the applications of nanoparticles in solving TE problems has yet to be realized. This review presents an overview of the diverse applications of various types of nanoparticles in TE applications and challenges that need to be overcome for nanotechnology to reach its full potential.