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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 &amp;lt; 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.<\/jats:p>","DOI":"10.1021\/nn5020787","type":"journal-article","created":{"date-parts":[[2014,7,2]],"date-time":"2014-07-02T12:53:14Z","timestamp":1404305594000},"page":"8050-8062","source":"Crossref","is-referenced-by-count":507,"title":["Injectable Graphene Oxide\/Hydrogel-Based Angiogenic Gene Delivery System for Vasculogenesis and Cardiac Repair"],"prefix":"10.1021","volume":"8","author":[{"given":"Arghya","family":"Paul","sequence":"first","affiliation":[{"name":"Harvard Medical School , , 65 Landsdowne Street , , ,","place":["Cambridge, Massachusetts, United States, 02139"]},{"name":"Harvard University , , , ,","place":["Boston, Massachusetts, United States, 02115"]},{"name":"Massachusetts Institute of Technology , , , ,","place":["Cambridge, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwarul","family":"Hasan","sequence":"additional","affiliation":[{"name":"Harvard Medical School , , 65 Landsdowne Street , , ,","place":["Cambridge, Massachusetts, United States, 02139"]},{"name":"Massachusetts Institute of Technology , , , ,","place":["Cambridge, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamood Al","family":"Kindi","sequence":"additional","affiliation":[{"name":"McGill University Health Centre, The Royal Victoria Hospital , , Room S8-73b, 687 Pine Avenue , , ,","place":["West Montreal, Quebec, Canada, H3A 1A1"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhilesh K.","family":"Gaharwar","sequence":"additional","affiliation":[{"name":"Texas A&M University , 5024 Emerging Technology Building , , ,","place":["College Station, Texas, United States, 77843"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijayaraghava T. 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