title: In vitro chemotaxis and tissue remodeling assays quantitatively characterize foreign body reaction.
abstract: Surgical implantation of a biomaterial triggers foreign-body-induced fibrous encapsulation. Two major mechanisms of this complex physiological process are (I) chemotaxis of fibroblasts from surrounding tissue to the implant region, followed by (II) tissue remodeling. As an alternative to animal studies, we here propose a process-aligned in vitro test platform to investigate the material dependency of fibroblast chemotaxis and tissue remodeling mediated by material-resident macrophages. Embedded in a biomimetic three-dimensional collagen hydrogel, chemotaxis of fibroblasts in the direction of macrophage-material-conditioned cell culture supernatant was analyzed by live cell imaging. A combination of statistical analysis with a complementary parameterized random walk model allowed quantitative and qualitative characterization of the cellular walk process. We thereby identified an increasing macrophage-mediated chemotactic potential ranking of biomaterials from glass over polytetrafluorethylene to titanium. To address long-term effects of bio-material-resident macrophages on fibroblasts in a three-dimensional microenvironment, we further studied tissue remodeling by applying macrophage-material-conditioned medium on fibrous in vitro tissue models. A high correlation of the in vitro tissue model to state of the art in vivo study data was found. Titanium exhibited a significantly lower tissue remodeling capacity compared to polytetrafluorethylene. With this approach, we identified a material dependency of both chemotaxis and tissue remodeling processes, strengthening knowledge on their specific contribution to the foreign body reaction.
authors.affiliation: University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine (TERM), Wuerzburg, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Jannasch
authors.affiliation: University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine (TERM), Wuerzburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Weigel
authors.affiliation: University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine (TERM), Wuerzburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Engelhardt
authors.affiliation: University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine (TERM), Wuerzburg, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Wiezoreck
authors.affiliation: University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine (TERM), Wuerzburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Gaetzner
authors.affiliation: University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine (TERM), Wuerzburg, Germany.|Translational Center Wuerzburg "Regenerative Therapies in Oncology and Musculoskeletal Disease" Wuerzburg branch of the Fraunhofer Institute Interfacial Engineering and Biotechnology, Wuerzburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Walles
authors.affiliation: University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine (TERM), Wuerzburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmitz
authors.affiliation: University Hospital Wuerzburg, Department Tissue Engineering and Regenerative Medicine (TERM), Wuerzburg, Germany.|Translational Center Wuerzburg "Regenerative Therapies in Oncology and Musculoskeletal Disease" Wuerzburg branch of the Fraunhofer Institute Interfacial Engineering and Biotechnology, Wuerzburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Hansmann
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D001672:Biocompatible Materials; D002633:Chemotaxis / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D005549:Foreign-Body Reaction / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D015233:Models, Statistical
chemical_list: D001672:Biocompatible Materials
keywords: Foreign body reaction; fibroblast chemotaxis; in vitro; quantitative characterization; tissue remodeling