title: The effect of matrix stiffness of injectable hydrogels on the preservation of cardiac function after a heart attack.
abstract: This study compares the effect of four injectable hydrogels with different mechanical properties on the post-myocardial infarction left ventricle (LV) remodeling process. The bioactive hydrogels were synthesized from Tetronic-fibrinogen (TF) and PEG-fibrinogen (PF) conjugates; each hydrogel was supplemented with two levels of additional cross-linker to increase the matrix stiffness as measured by the shear storage modulus (G'). Infarcts created by ligating the left anterior descending coronary artery in a rodent model were treated with the hydrogels, and all four treatment groups showed an increase in wall thickness, arterial density, and viable cardiac tissue in the peri-infarct areas of the LV. Echocardiography and hemodynamics data of the PF/TF treated groups showed significant improvement of heart function associated with the attenuated effects of the remodeling process. Multi-factorial regression analysis indicated that the group with the highest modulus exhibited the best rescue of heart function and highest neovascularization. The results of this study demonstrate that multiple properties of an injectable bioactive biomaterial, and notably the matrix stiffness, provide the multifaceted stimulation necessary to preserve cardiac function and prevent adverse remodeling following a heart attack.
authors.affiliation: Nanoscience and Nanotechnology Initiative, National University of Singapore, Singapore.
authors.forename: Marian
authors.initials: M
authors.lastname: Plotkin
authors.affiliation: Nanoscience and Nanotechnology Initiative, National University of Singapore, Singapore.
authors.forename: Srirangam Ramanujam
authors.initials: SR
authors.lastname: Vaibavi
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Abdul Jalil
authors.initials: AJ
authors.lastname: Rufaihah
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Venkateswaran
authors.initials: V
authors.lastname: Nithya
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Shachaf
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiac, Thoracic & Vascular Surgery, National University Heart Centre Singapore, National University Health System, Singapore. Electronic address: surtk@nus.edu.sg.
authors.forename: Theo
authors.initials: T
authors.lastname: Kofidis
authors.affiliation: Nanoscience and Nanotechnology Initiative, National University of Singapore, Singapore; Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address: dror@bm.technion.ac.il.
authors.forename: Dror
authors.initials: D
authors.lastname: Seliktar
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D004452:Echocardiography; D005109:Extracellular Matrix; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D020100:Hydrogels; D009203:Myocardial Infarction / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels
keywords: Injectable hydrogel; Matrix modulus; Mechanical properties; Minimally invasive; Myocardial infarction