TY  - JOUR
A1  - Lotz, C.
A1  - Kiesewetter, L.
A1  - Schmid, F. F.
A1  - Hansmann, J.
A1  - Walles, H.
A1  - Groeber-Becker, F.
T1  - Replacing the Draize eye test: impedance spectroscopy as a 3R method to discriminate between all GHS categories for eye irritation
JF  - Scientific Reports
N2  - Highly invasive animal based test procedures for risk assessment such as the Draize eye test are under increasing criticism due to poor transferability for the human organism and animal-welfare concerns. However, besides all efforts, the Draize eye test is still not completely replaced by alternative animal-free methods. To develop an in vitro test to identify all categories of eye irritation, we combined organotypic cornea models based on primary human cells with an electrical readout system that measures the impedance of the test models. First, we showed that employing a primary human cornea epithelial cell based model is advantageous in native marker expression to the primary human epidermal keratinocytes derived models. Secondly, by employing a non-destructive measuring system based on impedance spectroscopy, we could increase the sensitivity of the test system. Thereby, all globally harmonized systems categories of eye irritation could be identified by repeated measurements over a period of 7 days. Based on a novel prediction model we achieved an accuracy of 78% with a reproducibility of 88.9% to determine all three categories of eye irritation in one single test. This could pave the way according to the 3R principle to replace the Draize eye test.
KW  - biological models
KW  - electrical and electronic engineering
KW  - regenerative medicine
KW  - tissue engineering
KW  - toxicology
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177492
VL  - 8
IS  - 15049
ER  - 
TY  - JOUR
A1  - Radakovic, D.
A1  - Reboredo, J.
A1  - Helm, M.
A1  - Weigel, T.
A1  - Schürlein, S.
A1  - Kupczyk, E.
A1  - Leyh, R. G.
A1  - Walles, H.
A1  - Hansmann, J.
T1  - A multilayered electrospun graft as vascular access for hemodialysis
JF  - PLoS ONE
N2  - Despite medical achievements, the number of patients with end-stage kidney disease keeps steadily raising, thereby entailing a high number of surgical and interventional procedures to establish and maintain arteriovenous vascular access for hemodialysis. Due to vascular disease, aneurysms or infection, the preferred access—an autogenous arteriovenous fistula—is not always available and appropriate. Moreover, when replacing small diameter blood vessels, synthetic vascular grafts possess well-known disadvantages. A continuous multilayered gradient electrospinning was used to produce vascular grafts made of collagen type I nanofibers on luminal and adventitial graft side, and poly-ɛ-caprolactone as medial layer. Therefore, a custom-made electrospinner with robust environmental control was developed. The morphology of electrospun grafts was characterized by scanning electron microscopy and measurement of mechanical properties. Human microvascular endothelial cells were cultured in the graft under static culture conditions and compared to cultures obtained from dynamic continuous flow bioreactors. Immunofluorescent analysis showed that endothelial cells form a continuous luminal layer and functional characteristics were confirmed by uptake of acetylated low-density-lipoprotein. Incorporation of vancomycin and gentamicin to the medial graft layer allowed antimicrobial inhibition without exhibiting an adverse impact on cell viability. Most striking a physiological hemocompatibility was achieved for the multilayered grafts.
KW  - collagens
KW  - polymers
KW  - vascular surgery
KW  - endothelial cells
KW  - cell cultures
KW  - blood
KW  - antibiotics
KW  - scanning electron microscopy
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159102
VL  - 12
IS  - 10
ER  -