Beren Atac Wagegg

Dr. Beren Atac Wagegg is a Senior Scientist and Business Development Manager at TissUse GmbH and has been a driving force in the realm of multi-organ-chip technology since joining the pioneering company in 2014. Holding a Ph.D. in Medical Biotechnology from TU Berlin, Germany, Dr. Atac Wagegg's expertise lies in the dynamic intersection of tissue engineering and the avant-garde development of multi-organ-chip-based prototypes. Her profound contributions extend to diverse applications, notably in predictive toxicology, efficacy testing, and the meticulous evaluation of ADME profiles in vitro. Dr. Atac Wagegg has been instrumental in the establishment of cutting-edge chip-based assays, particularly tailored for the Cosmetic industry. Her core role is to adeptly coordinate and manage a spectrum of research projects. Notably, she oversees projects under Contract Development, steering efforts toward the standardization of chip-based assays tailored to the industry. TissUse is the pioneering force in the field of multi-organ-chip technology, driving innovation since 2010. These platforms not only contribute significantly to predicting toxicity, ADME profiles, and efficacy in vitro but also embody the company's commitment to transforming preclinical insights on a systemic level using human tissue. Dr. Atac Wagegg's profound impact underscores her commitment to advancing the frontiers of medical biotechnology and paving the way for a future that minimizes reliance on traditional laboratory animal testing methodologies.

NextGen Basel 1

Multi-Organ-on-Chip in Safety and Efficacy Testing: Unraveling Application Scenario Impact on Bioavailability and Effects with Skin, Liver, and Thyroid Models

Beren Atac Wagegg 2, Jochen Kühnl 1, Thi-Phuong Tao 2, Katrin Brandmair 1, Silke Gerlach 1, Julia Przibilla 5, Fredy Kern 5, Camille Genies 6, Carine Jaques-Jamin 6, Abdulkarim Najjar 1, Ed LeCluyse 3, Vignesh Viswanathan 2, Eda Rogers 4, Andreas Schepky 1, Uwe Marx 2, Ilka Maschmeyer 2, Nicola J. Hewitt 7

1. 1 Beiersdorf AG, Unnastraße 48, D-20253 Hamburg, Germany
2. 2 TissUse GmbH, Oudenarder Str. 16, D-13347 Berlin, Deutschland
3. 3 LifeNet Health, 6 Davis Drive, Suite 155, P.O. Box 12878, Research Triangle Park, NC 27709, USA
4. 4 LifeNet Health, 1864 Concert Drive, Virginia Beach, Virginia 23453
5. 5 Pharmacelsus GmbH, Science Park 2, D-66123 Saarbrücken, Germany
6. 6 Pierre Fabre Dermo-Cosmétique, 3 avenue Hubert Curien, Toulouse, France.
7. 7 Cosmetics Europe, Avenue Herrmann-Debroux 40, 1160 Auderghem, Belgium

Microphysiological systems (MPS) constitute promising in vitro platforms for the assessment of systemic toxicity as they provide holistic information on intrinsically tied toxicokinetic and toxicodynamic properties of chemicals. We evaluated the use of MPS to elucidate the influence of application scenarios on the bioavailability, metabolic fate, and biological effects of (cosmetic) chemicals. The integration of reconstructed human skin tissue or native human skin in the MPS is key to mimicking the skin penetration and metabolism of topically applied chemicals. TissUse HUMIMIC platform enables long-term maintenance of skin equivalents in combination with additional tissue equivalents. Initially, we worked with EpiDerm™ and liver spheroids to explore the model´s transferability and robustness based on well-characterized substances. In addition to a high inter- and intra-lab reproducibility, the results demonstrated diverging effects of single and repeated application on metabolic fate and liver metabolizing enzyme expression. Furthermore, we assessed the impact of first-pass skin metabolism to support route-to-route exposure considerations for risk assessment. For example, a low dose of the hair dye 4-amino-2-hydroxytoluene (AHT) was significantly detoxified by N-acetylation in the skin.

The dose finding required consideration of the skin models´ metabolic capacity which determined the ratio of AHT-N-acetylated AHT. This closely recapitulates results from in vivo animal studies fundamental to a favorable SCCS opinion on the safe use of AHT. Most recent work incorporated a third in vitro tissue (thyroid) based on the development of a new protocol to generate functional thyroid follicle-like organoids from cryopreserved thyrocytes. HUMIMIC 3-organ chip was employed to optimize the culture conditions for thyroid organoid formation and subsequent co-culture were carried out to better emulate biological functionality. Daidzein and its structural analogue, genistein, both inhibited thyroxine (T4) and 3,3’,5-triiodothyronine (T3) production, in an assay that was qualified using the thyroid peroxidase inhibitor, methimazole. For daidzein, we could determine a “safe dose” which did not alter T3 and T4 levels which is in the range of SCCS´s recent opinion for daidzein. We conclude that MPS systems are promising options to inform on exposure scenario-dependent toxicokinetics and route-specific biological effects of test chemicals.