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In vitro chemotaxis and tissue remodeling assays quantitatively characterize foreign body reaction

 
: Jannasch, Maren; Weigel, Tobias; Engelhardt, Lisa; Wiezoreck, Judith; Gaetzner, Sabine; Walles, Heike; Schmitz, Tobias; Hansmann, Jan

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Alternatives to animal experimentation : ALTEX 34 (2017), No.2, pp.253-266
ISSN: 1868-596X
ISSN: 0946-7785
English
Journal Article
Fraunhofer IGB ()
foreign body reaction; fibroblast chemotaxis; in vitro; quantitative characterization; tissue remodeling

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 an process-aligned in vitrotest 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 direction of macrophage-material-incubated cell culture supernatant was analysed 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 from tested biomaterials glass over polytetrafluorethylene to titanium. To address long-term effects of biomaterial-resident macrophages on fibroblasts in a three-dimensional microenvironment, we further studied tissue remodeling by applying macrophage-material-incubated medium on fibrous in vitro tissue models. A high correlation to state of the art in vivo studies to the proposed in vitro tissue model was found. Titanium exhibited significantly lower tissue remodeling capacity compared to polytetrafluorethylene. By this approach we identified a material dependency for both processes chemotaxis and tissue remodeling, strengthening their specific contribution to foreign body reaction.

: http://publica.fraunhofer.de/documents/N-426265.html