title: Timing effect of intramyocardial hydrogel injection for positively impacting left ventricular remodeling after myocardial infarction.
abstract: Intramyocardial injection of various injectable hydrogel materials has shown benefit in positively impacting the course of left ventricular (LV) remodeling after myocardial infarction (MI). However, since LV remodeling is a complex, time dependent process, the most efficacious time of hydrogel injection is not clear. In this study, we injected a relatively stiff, thermoresponsive and bioabsorbable hydrogel in rat hearts at 3 different time points - immediately after MI (IM), 3 d post-MI (3D), and 2 w post-MI (2W), corresponding to the beginnings of the necrotic, fibrotic and chronic remodeling phases. The employed left anterior descending coronary artery ligation model showed expected infarction responses including functional loss, inflammation and fibrosis with distinct time dependent patterns. Changes in LV geometry and contractile function were followed by longitudinal echocardiography for 10 w post-MI. While all injection times positively affected LV function and wall thickness, the 3D group gave better functional outcomes than the other injection times and also exhibited more local vascularization and less inflammatory markers than the earlier injection time. The results indicate an important role for injection timing in the increasingly explored concept of post-MI biomaterial injection therapy and suggest that for hydrogels with mechanical support as primary function, injection at the beginning of the fibrotic phase may provide improved outcomes.
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Tomo
authors.initials: T
authors.lastname: Yoshizumi
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Jiang
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Amore
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Sakaguchi
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Tchao
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: wagnerwr@upmc.edu.
authors.forename: William R
authors.initials: WR
authors.lastname: Wagner
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D007267:Injections; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011917:Rats, Inbred Lew; D013997:Time Factors; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000199:Actins; D016207:Cytokines; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D018836:Inflammation Mediators; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C498862:Acta2 protein, rat
keywords: Cardiac tissue engineering; Hydrogel; Injectable materials; Intervention timing; Myocardial infarction