TY  - JOUR
A1  - Groeber, Florian
A1  - Schober, Lena
A1  - Schmid, Freia F.
A1  - Traube, Andrea
A1  - Kolbus-Hernandez, Silvia
A1  - Daton, Karolina
A1  - Hoffmann, Sebastian
A1  - Petersohn, Dirk
A1  - Schaefer-Korting, Monika
A1  - Walles, Heike
A1  - Mewes, Karsten R.
T1  - Catch-up validation study of an in vitro skin irritation test method based on an open source reconstructed epidermis (phase II)
JF  - Toxicology in Vitro
N2  - To replace the Draize skin irritation assay (OECD guideline 404) several test methods based on reconstructed human epidermis (RHE) have been developed and were adopted in the OECD test guideline 439. However, all validated test methods in the guideline are linked to RHE provided by only three companies. Thus,the availability of these test models is dependent on the commercial interest of the producer. To overcome this limitation and thus to increase the accessibility of in vitro skin irritation testing, an open source reconstructed epidermis (OS-REp) was introduced. To demonstrate the capacity of the OS-REp in regulatory risk assessment, a catch-up-validation study was performed. The participating laboratories used in-house generated OS-REp to assess the set of 20 reference substances according to the performance standards amending the OECD test guideline 439. Testing was performed under blinded conditions. The within-laboratory reproducibility of 87% and the inter-laboratory reproducibility of 85% prove a high reliability of irritancy testing using the OS-REp protocol. In addition, the prediction capacity was with an accuracy of 80% comparable to previous published RHE based test protocols. Taken together the results indicate that the OS-REp test method can be used as a standalone alternative skin irritation test replacing the OECD test guideline 404.
KW  - Model
KW  - Chemicals
KW  - Assay
KW  - Episkin
KW  - Vivo
KW  - RHE
KW  - In vitro skin irritation testing
KW  - Open source reconstructed epidermis
KW  - Validation
KW  - Alternative test methods
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187311
VL  - 36
ER  - 
TY  - JOUR
A1  - Lotz, Christian
A1  - Schmid, Freia F.
A1  - Rossi, Angela
A1  - Kurdyn, Szymon
A1  - Kampik, Daniel
A1  - De Wever, Bart
A1  - Walles, Heike
A1  - Groeber, Florian K.
T1  - Alternative Methods for the Replacement of Eye Irritation Testing
JF  - ALTEX - Alternatives to Animal Experimentation
N2  - In the last decades significant regulatory attempts were made to replace, refine and reduce animal testing to assess the risk of consumer products for the human eye. As the original in vivo Draize eye test is criticized for limited predictivity, costs and ethical issues, several animal-free test methods have been developed to categorize substances according to the global harmonized system (GHS) for eye irritation. This review summarizes the progress of alternative test methods for the assessment of eye irritation. Based on the corneal anatomy and current knowledge of the mechanisms causing eye irritation, different ex vivo and in vitro methods will be presented and discussed with regard to possible limitations and status of regulatory acceptance. In addition to established in vitro models, this review will also highlight emerging, full thickness cornea models that might be suited to predict all GHS categories.
KW  - eye irritation testing
KW  - alternatives
KW  - Draize eye test
KW  - OECD guideline
KW  - corneal equivalent
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164444
VL  - 33
IS  - 1
ER  - 
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  -