TY - JOUR A1 - Weigel, Tobias A1 - Schmitz, Tobias A1 - Pfister, Tobias A1 - Gaetzner, Sabine A1 - Jannasch, Maren A1 - Al-Hijailan, Reem A1 - Schürlein, Sebastian A1 - Suliman, Salwa A1 - Mustafa, Kamal A1 - Hansmann, Jan T1 - A three-dimensional hybrid pacemaker electrode seamlessly integrates into engineered, functional human cardiac tissue in vitro JF - Scientific Reports N2 - Pacemaker systems are an essential tool for the treatment of cardiovascular diseases. However, the immune system’s natural response to a foreign body results in the encapsulation of a pacemaker electrode and an impaired energy efficiency by increasing the excitation threshold. The integration of the electrode into the tissue is affected by implant properties such as size, mechanical flexibility, shape, and dimensionality. Three-dimensional, tissue-like electrode scaffolds render an alternative to currently used planar metal electrodes. Based on a modified electrospinning process and a high temperature treatment, a conductive, porous fiber scaffold was fabricated. The electrical and immunological properties of this 3D electrode were compared to 2D TiN electrodes. An increased surface of the fiber electrode compared to the planar 2D electrode, showed an enhanced electrical performance. Moreover, the migration of cells into the 3D construct was observed and a lower inflammatory response was induced. After early and late in vivo host response evaluation subcutaneously, the 3D fiber scaffold showed no adverse foreign body response. By embedding the 3D fiber scaffold in human cardiomyocytes, a tissue-electrode hybrid was generated that facilitates a high regenerative capacity and a low risk of fibrosis. This hybrid was implanted onto a spontaneously beating, tissue-engineered human cardiac patch to investigate if a seamless electronic-tissue interface is generated. The fusion of this hybrid electrode with a cardiac patch resulted in a mechanical stable and electrical excitable unit. Thereby, the feasibility of a seamless tissue-electrode interface was proven. KW - biomedical materials KW - cardiac device therapy KW - hybrid pacemaker Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177368 VL - 8 IS - 14545 ER - TY - JOUR A1 - Jannasch, Maren A1 - Weigel, Tobias A1 - Engelhardt, Lisa A1 - Wiezoreck, Judith A1 - Gaetzner, Sabine A1 - Walles, Heike A1 - Schmitz, Tobias A1 - Hansmann, Jan T1 - \({In}\) \({vitro}\) chemotaxis and tissue remodeling assays quantitatively characterize foreign body reaction JF - ALTEX - Alternatives to Animal Experimentation N2 - 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 biomaterial-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. KW - medicine KW - foreign body reaction KW - fibroblast chemotaxis KW - tissue remodeling KW - in vitro KW - quanititative characterization Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172080 VL - 34 IS - 2 ER - TY - JOUR A1 - Jannasch, Maren A1 - Gaetzner, Sabine A1 - Weigel, Tobias A1 - Walles, Heike A1 - Schmitz, Tobias A1 - Hansmann, Jan T1 - A comparative multi-parametric in vitro model identifies the power of test conditions to predict the fibrotic tendency of a biomaterial JF - Scientific Reports N2 - Despite growing effort to advance materials towards a low fibrotic progression, all implants elicit adverse tissue responses. Pre-clinical biomaterial assessment relies on animals testing, which can be complemented by in vitro tests to address the Russell and Burch’s 3R aspect of reducing animal burden. However, a poor correlation between in vitro and in vivo biomaterial assessments confirms a need for suitable in vitro biomaterial tests. The aim of the study was to identify a test setting, which is predictive and might be time- and cost-efficient. We demonstrated how sensitive in vitro biomaterial assessment based on human primary macrophages depends on test conditions. Moreover, possible clinical scenarios such as lipopolysaccharide contamination, contact to autologous blood plasma, and presence of IL-4 in an immune niche influence the outcome of a biomaterial ranking. Nevertheless, by using glass, titanium, polytetrafluorethylene, silicone, and polyethylene representing a specific material-induced fibrotic response and by comparison to literature data, we were able to identify a test condition that provides a high correlation to state-of-the-art in vivo studies. Most important, biomaterial ranking obtained under native plasma test conditions showed a high predictive accuracy compared to in vivo assessments, strengthening a biomimetic three-dimensional in vitro test platform. KW - inflammation KW - experimental models of disease KW - biomaterial tests KW - in vitro Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170908 VL - 7 IS - 1689 ER -