title: Enhanced infarct stabilization and neovascularization mediated by VEGF-loaded PEGylated fibrinogen hydrogel in a rodent myocardial infarction model.
abstract: Most tissue engineering therapies require biomaterials that are able to induce an angiogenic response to support tissue regeneration. In addition angiogenic growth factor signaling plays an essential role in controlling the process of angiogenesis and matrices have the potential of regulating the concentration of growth factors within the cellular microenvironment. Here we demonstrated myocardial protection and improved post-infarct vascularization of the infarcted hearts using a biosynthetic injectable hydrogel consisting of polyethylene glycol and fibrinogen (PEG-fibrinogen) loaded with vascular endothelial growth factor-A (VEGF-A). Our data revealed PEG-fibrinogen hydrogel was able to store and release VEGF-A in a sustained and controlled fashion. Upon injection after coronary artery ligation, the VEGF-loaded hydrogel significantly improved arteriogenesis and cardiac performance at 4 weeks post-infarction. The results support the future application of PEG-fibrinogen for regulating growth factor signaling in cellular microenvironment and may demonstrates a new strategy for cardiovascular repair with potential for future clinical applications.
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. surraj@nus.edu.sg
authors.forename: Abdul Jalil
authors.initials: AJ
authors.lastname: Rufaihah
authors.forename: Srirangam Ramanujam
authors.initials: SR
authors.lastname: Vaibavi
authors.forename: Marian
authors.initials: M
authors.lastname: Plotkin
authors.forename: Jiayi
authors.initials: J
authors.lastname: Shen
authors.forename: Venkateswaran
authors.initials: V
authors.lastname: Nithya
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Dror
authors.initials: D
authors.lastname: Seliktar
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kofidis
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004452:Echocardiography; D005340:Fibrinogen / Q000737:chemistry*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D009203:Myocardial Infarction / Q000628:therapy*; D011092:Polyethylene Glycols / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D005340:Fibrinogen
keywords: Cardiac tissue engineering; Growth factors; Hydrogel; In vivo test