title: The enzymatic degradation of scaffolds and their replacement by vascularized extracellular matrix in the murine myocardium.
abstract: Replacement of injured myocardium by cell-based degradable scaffolds is a novel approach to regenerate myocardium. Understanding the foreign body reaction (FBR) induced by the scaffold is requisite to predict unwanted site effects or implant failure. We evaluated the FBR against a biodegradable scaffold applied on injured myocardium in mice. Cryolesions and collagen type I scaffolds (Col-I) were applied to the left ventricle of mice. Cell infiltration, neovascularization, collagen deposition, matrix metalloproteinase (MMP-8) expression, enzymatic activity and scaffold degradation were determined at different time points (2-70 days). Infiltration of mainly macrophages, neutrophils and blood vessels was completed within 14 days. High numbers of neutrophils accumulated around the Col-I fibers and degradation of Col-I fibers into small fragments was observed on day 14. Active MMP-8 co-localized with the neutrophils on day 14, indicating enzymatic degradation of Col-I by neutrophil collagenase. Highly vascularized extracellular matrix remained at day 70. No differences were observed in the FBR to Col-I after application on healthy or injured myocardium. The FBR had no adverse effects on the adjacent myocardial tissue. In conclusion, cardiac scaffolds are degraded by MMP-8 and replaced by vascularized extracellular matrix during the FBR on injured myocardium.
authors.affiliation: Department of Pathology and Laboratory Medicine, Faculty of Medical Sciences, University Medical Center Groningen, University of Groningen, Medical Biology section, The Netherlands. M.van.Amerongen@med.rug.nl
authors.forename: Machteld J
authors.initials: MJ
authors.lastname: van Amerongen
authors.forename: Martin C
authors.initials: MC
authors.lastname: Harmsen
authors.forename: Arjen H
authors.initials: AH
authors.lastname: Petersen
authors.forename: Geert
authors.initials: G
authors.lastname: Kors
authors.forename: Marja J A
authors.initials: MJ
authors.lastname: van Luyn
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005549:Foreign-Body Reaction; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D011093:Polyethylene Terephthalates / Q000378:metabolism; D012038:Regeneration; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D024042:Collagen Type I; D011093:Polyethylene Terephthalates; D020784:Matrix Metalloproteinase 8