title: Biomaterial Encapsulation Is Enhanced in the Early Stages of the Foreign Body Reaction During Conditional Macrophage Depletion in Transgenic Macrophage Fas-Induced Apoptosis Mice<sup/>.
abstract: Macrophages are pivotal cells during the foreign body reaction (FBR), as they orchestrate the proinflammatory microenvironment inside and around biomaterials by secretion of inflammatory mediators. Furthermore, they are responsible for the degradation of biomaterials and are thought to instruct the fibroblasts that generate a fibrous capsule around implanted biomaterials. In this study, we investigated the events during the FBR when macrophages are not present. Hexamethylenediisocyanate crosslinked collagen scaffolds were implanted in "Macrophage Fas-Induced Apoptosis" mice, which allow "on demand" macrophage depletion. We observed that macrophage depletion completely inhibited inflammatory ingrowth into the scaffolds and resulted in an increased capsule size. Quantitative polymerase chain reaction analysis revealed decreased expression levels of proinflammatory mediators such as TNFα and IL1β, and increased expression levels of collagens and fibroblast-stimulating growth factors such as EGF, FGF1, FGF2, and TGFα. Our results indicate that macrophages are indeed crucial for the generation of a proinflammatory microenvironment inside implanted biomaterials, leading to inflammatory ingrowth. In contrast, macrophages do not appear to be important for the generation of a fibrous capsule around implanted biomaterials. In fact, our data suggest that the macrophages present in the capsule might instruct the surrounding fibroblasts to produce less fibroblast-stimulating factors and less collagens.
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands .
authors.forename: Ruud A
authors.initials: RA
authors.lastname: Bank
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands .
authors.forename: Jurjen
authors.initials: J
authors.lastname: Zandstra
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands .
authors.forename: Hilde
authors.initials: H
authors.lastname: Room
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands .
authors.forename: Arjen H
authors.initials: AH
authors.lastname: Petersen
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands .
authors.forename: Sander M
authors.initials: SM
authors.lastname: van Putten
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001672:Biocompatible Materials / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005549:Foreign-Body Reaction / Q000235:genetics / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009929:Organ Size; D015203:Reproducibility of Results; D054457:Tissue Scaffolds / Q000737:chemistry; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; C491899:Fas protein, mouse; D018836:Inflammation Mediators; D019014:fas Receptor
keywords: biomaterials; fibrosis; foreign body reaction; macrophage depletion; macrophages