title: Timing underpins the benefits associated with injectable collagen biomaterial therapy for the treatment of myocardial infarction.
abstract: Injectable hydrogel biomaterials are promising therapies to promote repair and regeneration post-myocardial infarction (MI). However, the timing of delivery and the mechanisms through which biomaterial treatments confer their benefits are translational issues that remain to be addressed. We assessed the efficacy of an injectable collagen matrix at 3 different delivery time points post-MI. Infarcted mice received the matrix or control (saline) treatment at 3 h, 1 week or 2 weeks after MI. The earlier treatment delivery better prevented negative ventricular remodeling and long-term deterioration of cardiac function (up to 3 months), whereas waiting longer to administer the matrix (1 and 2 weeks post-MI) reduced the therapeutic effects. Collagen matrix delivery did not stimulate an inflammatory response acutely and favorably modulated inflammation in the myocardium long-term. We found that the matrix interacts with the host tissue to alter the myocardial cytokine profile, promote angiogenesis, and reduce fibrosis and cell death. This work highlights that the timing of delivery can significantly affect the ability of an injectable hydrogel to protect the post-MI environment, which will be an important consideration in the clinical translation of cardiac biomaterial therapy.
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa K1H 8M5, Canada.
authors.forename: Nick J R
authors.initials: NJ
authors.lastname: Blackburn
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa K1H 8M5, Canada.
authors.forename: Tanja
authors.initials: T
authors.lastname: Sofrenovic
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa K1H 8M5, Canada.
authors.forename: Drew
authors.initials: D
authors.lastname: Kuraitis
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa K1H 8M5, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmadi
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: McNeill
authors.affiliation: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.affiliation: Atherosclerosis, Genomics and Cell Biology Group, University of Ottawa Heart Institute, K1Y 4W7, Canada.
authors.forename: Katey J
authors.initials: KJ
authors.lastname: Rayner
authors.affiliation: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa K1H 8M5, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Ruel
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa K1Y 4W7, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa K1H 8M5, Canada. Electronic address: esuuronen@ottawaheart.ca.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000627:therapeutic use*; D003094:Collagen; D004452:Echocardiography; D005109:Extracellular Matrix / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy*
chemical_list: D001672:Biocompatible Materials; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003094:Collagen
keywords: Collagen; Extracellular matrix; Fibrosis; Heart; Hydrogel