TY  - JOUR
A1  - Groeber, Florian
A1  - Engelhardt, Lisa
A1  - Lange, Julia
A1  - Kurdyn, Szymon
A1  - Schmid, Freia F.
A1  - Rücker, Christoph
A1  - Mielke, Stephan
A1  - Walles, Heike
A1  - Hansmann, Jan
T1  - A First Vascularized Skin Equivalent as an Alternative to Animal Experimentation
JF  - ALTEX - Alternatives to Animal Experimentation
N2  - Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin & eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research.
KW  - alternative to animal testing
KW  - skin equivalents
KW  - tissue engineering
KW  - vascularization
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164438
VL  - 33
IS  - 4
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  -