Particles@barriers

The aim of our group is to acquire a mechanistic understanding on the interaction of particulate materials with biological barriers. In particular, we are interested in the correlation of physicochemical particle properties with barrier translocation and biological effects in order to support the safe design of particles and the development of novel particle-based therapeutic concepts.

The placental barrier is a key focus of the group considering the exceptional vulnerability of the developing conceptus and the substantial knowledge gap in this field of research. To obtain predictive results, we develop and use advanced human in vitro and ex vivo placental models, which take into account the unique structure/function and the particular microenvironment of the human placenta. Our expertise encompasses dual ex vivo placenta perfusion studies, co-culture transwell systems, organotypic 3D microtissue models, isolation of primary cells (e.g. trophoblasts), placenta explants (first and third trimester) as well as strong competences in working with particulate materials.

Development of advanced barrier models

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We develop and use advanced in vitro and ex vivo models to address particle effects and translocation at biological barriers, focussing on the placenta, intestine and lung. Importantly, we employ tissues or cells of human origin to circumvent uncertainties in extrapolation of animal data. Our strategies to improve the predictive value of the models include the use of primary cells, co-cultures, inclusion of mucus, 3D models or the recreation of a dynamic microenvironment. In the last years, we have succesfully developed and verified two first-in-field advanced in vitro models for the human placental barrier (organotypic 3D placental co-culture microtissues and a co-culture transwell model) and gained extensive expertise in the ex vivo perfusion of human term placentas. Recently, we contributed to the development of a novel microphysiological co-culture model of the maternal-placental-embryonic axis for early developmental toxicity assessment. This model is currently pushed into a fully human-based model for predicitve developmental toxicity assessment. Furthermore, since commercial microporous membranes are often considerably blocking nanoparticle translocation, we have exploited novel electrospun and ultrathin graphene membranes. Currently, we are engaged in the development, refinement and validation of new approach methodologies/models (NAMs) for next generation safety and efficacy assessment of advanced (nano)materials and compounds, centering on human-based tissue models covering relvant environmental, occupational and medical exposure routes (e.g. skin, lung, intestine and placenta) as well as disease conditions (infection, asthma). This research has previously received funding  from the 7th Framework Program of the European Comission (EC-FP7-MARINA-263215,EC-FP7-NANOSOLUTIONS-309329, EC-H2020-FET-Graphene Core2/3-785219/881603) and the BMBF-project NanoUmwelt (03X0150) and is currently supported by ProCare Foundation and HEurope projects MACRAME and CHIASMA.

Understanding particles-barrier interactions

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Nanoscale materials exhibit unique properties and are envisaged to enable a wealth of novel applications in many fields. A comprehensive understanding of potential human health risks is a prerequisite to the safe and sustainable use of these promising materials.

Biological barriers perform essential protective and supportive functions and are thus potentially prone to damage from nanomaterials exposure.  In addition, understanding if and how particle properties can be employed to steer particle barrier interaction and effects is a prerequisite for the development of safe and effective particle-based therapies e.g. to treat the mother, the fetus or placental disorders with reduced off-target effects. We aim to achieve new mechanistic insights into particle-barrier interactions using our advanced biobarrier models, extensive material knowhow and access to state-of-the art analytics. Besides acute and long-term effects, we further expand our reserach to include disease models, co-exposure of nanomaterials and xenobiotics and indirect developmental toxicity mechanisms. We are currently researching into the impact of micro/nanoplastic health hazards including potential immunomodulatory effects at the placenta that could prime for allergies in later life. In a second project, we are developing intelligent single-atom nanozymes to treat gestational inflammation with a particular focus on assessing the safety and efficacy of these particles at the maternal-fetal interface$. This research is supported by funding from Swiss National Science Foundation (206059) and foundations (Heubergstiftung, Eduard Aeberhardt Stiftung) and received previous funding from the SNSF (31003A-179337), the 7th Framework Program of the European Comission (EC-FP7-MARINA-263215 and EC-FP7-NANOSOLUTIONS-309329) and the BMBF-project NanoUmwelt (03X0150).

2D and Graphene related materials@barriers

Graphene, graphene-related materials (GRM) and other 2D materials exhibit enormous technological potential, especially in the field of electronics, photonics, optoelectronics and composites, but also for biomedical applications. Nevertheless, the GRM safety landscape is not fully explored yet. The aim of our activities within the Graphene flagship project is to obtain a systematic understanding of the impact of 2D/GRM on human cells and biological barriers with respect to the physicochemical properties of the materials. Current investigations focus on the air-blood barrier in the lungs, the intestinal barrier and the placental barrier. Moreover, we investigate the release of 2D/GRMs from reinforced composites upon mechanical abrasion or thermal decomposition. This research is supported by funding from European Union 7th Framework Program Graphene Flagship project (EU-Graphene Flagship n°604391), the EU Horizon2020 Framework Graphene Flagship project GrapheneCore1, Core 2 and Core 3 (n°696656 and 785219 and n°881603) and the Swiss National Science Foundation (169207).

Dr. Tina Buerki-Thurnherr, Group Leader Particles@barriers

, +41 58 765 76 96

Alma Mater: ETH Zurich

Keywords: Nanotoxicology, Nanoparticle Translocation, Placenta, Advanced In Vitro Models, Primary Cell Culture

 

Dr. Govind Gupta, Scientist

Alma Mater: Ahmedabad University, Lucknow, India

Keywords: Nanosafety, environmental sustainability,ecotoxicological science

 

Dr. Beatrice Brugger, Postdoc

beatrice.brugger@empa.ch

Alma Mater: MedUni Graz, Austria

Keywords: Placenta, new approach methodologies (NAMs), developmental toxicity

 

Nikolaos Tagaras, PhD Student

Alma Mater: MSc, Karolinska Institutet

Keywords: Nanosafety, Nanomedicine, Placental barrier

 

Manon Murdeu, PhD Student

Alma Mater: MSc, University of Siena

Keywords: Placental barrier, Advanced co-culture models, microphysiological chip, developmental toxicity

 

Yvette Hannig, Technical Expert

Keywords: Ex vivo Placenta Perfusion, Nanotoxicology, Microscopy, Cell Biology

 

Sarah Boentges, Technical Expert

Keywords: Ex vivo Placenta Perfusion, Nanotoxicology, Microscopy, Cell and Molecular Biology

 

 

 

 

 

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Alumni

Dr. Lea Furer, ETH Zurich, PhD Student 2018-2022

Dr. Battuja Dugershaw-Kurzer, ETH Zurich, PhD Student, 2018-2022

Ms. Beatrice Brugger, MedUni Graz, Guest PhD, 2022

Dr. Savvina Chortarea, AMI Fribourg, Postdoc 2017-2021

Mr. Victor Fuster-Pozo, Fachhochschule Nordostschweiz FHNW, MSc Student, 2021

Dr. Woranan Netkueakul, ETH Zurich, PhD Student 2017-2021

Ms. Angela Diaz Abad, Universidad de Castilla-La Mancha. UCLM, MSc Student, 2020-2021

Ms. Daria Korejwo, AMI Fribourg, PhD Student, 2016-2020

Dr. Claudia Hempt, ETH Zurich, PhD Student, 2016-2020

Mr. Ogul Can Kuru, Polytecnico di Milano, MSc Student, 2019

Mr. Pius Manser, Technical expert, 1984-2019

Dr. Leonie Aengenheister, ETH Zurich, PhD Student 2015-2018; Postdoc Empa: 2019-2021

Mr. Erminio Di Renzo, ETH Zurich, MSc Student 2017-2018

Dr. Melanie Kucki, University of Kassel, Research Associate 2013-2017

Dr. Carina Muoth, University of Zurich, PhD Student 2013-2016

Mr. Chasper Gmünder, ETH Zurich, Project student 2014

Link to full publication list

Lin H., Buerki-Thurnherr T., Kaur J., Wick P., Pelin M., Tubaro A., Carniel FC., Tretiach M., Flahaut E., Iglesias D., Vazquez E., Cellot G., Ballerini L., Castagnola V., Benfenati F., Armirotti A., Sallustrau A., Keck M., Taran F., Bussy C., Vranic S., Kostarelos K., Connolly M., Navas JM., Mouchet F., Gauthier L., Baker J., Suarez-Merino B., Kanerva T., Prato M., Fadeel B., Bianco A. (2024). Environmental and health impact of graphene and other two-dimensional materials: A graphene flagship perspective. ACS Nano  2024, 18, 8, 6038–6094

Gupta G., Wang Z., Kissling VM., Gogos A., Wick P., Buerki-Thurnherr T. (2024). Boron nitride nanosheets induce lipid accumulation and autophagy in human alveolar lung epithelial cells cultivated at air-liquid interface. Small. doi.org/10.1002/smll.202308148

Dorey F., Furer L.A., Zehnder S., Furrer R., Brönnimann R., Shorubalko I.,  Tina Buerki-Thurnherr. (2023). Ultralarge suspended and perforated graphene membranes for cell culture applications. Mater Chem B. 2023, 11, 10097 - 10107

Chortarea S., Gupta G.S., Saarimäki L.A., Netkueakul W., Manser P., Aengenheister L., Wichser A., Fortino V., Wick P., Greco D., Buerki-Thurnherr T. (2023). Transcriptomic profiling reveals differential cellular response to copper oxide nanoparticles and polystyrene nanoplastics in perfused human placenta. Environmental International, doi: 10.1016/j.envint.2023.108015

Englert F.H., Mueller F.A., Dugershaw-Kurzer B., Kissling V.M., Boentges S., Gupta G.S., Fontan G.A., Diedrich S., Suter-Dick L., Sturla S.J., Buerki-Thurnherr T. (2023). Environmentally relevant UV-light weathering of polystyrene micro- and nanoplastics promotes hepatotoxicity in a human cell line. Environmental Science:Nano. 2023,10, 1644-1659

D. Korejwo, S. Chortarea, C. Louka, M. Buljan, B. Rothen-Rutishauser, P. Wick, T. Buerki-Thurnherr. (2023). Gene expression profiling of human macrophages after graphene oxide and graphene nanoplatelets treatment reveals particle-specific regulation of pathways. NanoImpact, 27:100452

LA. Furer., A. Díaz Abad, P. Manser, Y. Hannig, S. Schuerle, G. Fortunato, T. Buerki-Thurnherr. (2022). Novel electrospun chitosan/PEO membrands for more predicitive nanoparticle transport studies at biological barriers. Nanoscale, 14, 12136 - 12152

W. Netkueakul, S.Chortarea, K. Kulthong, L. Hao, G. Qiu, M. Jovic, S. Gaan, Y. Hannig, T. Buerki-Thurnherr, P. Wick, J. Wang. (2022). Airborne emissions from combustion of graphene nanoplatelet/epoxy composites and their cytotoxicity on lung cells via air-liquid interface cell exposure in vitro. NanoImpact, 27, 100414

S. Chortarea, OC. Kuru, Netkueakul W., Pelin M., S. Keshavan, Z. Song, B. Ma, J. Gómes, EV. Abalos, LA. de Luna, T. Loretgh, A. Fordham, M. Drummond, N. Kontis, G. Anagnostopoulos, G. Paterakis, P. Cataldi, A. Tubaro, C. Galiotis, I. Kinloch, B. Fadeel, C. Busy, K. Kostarelos, T. Buerki-Thurnherr, M. Prato, A. Bioanco, P. Wick. (2022). Hazard assessment of abraded thermoplastic composites reinforced with reduced graphene oxide. Journal of Hazardous Materials, 435(6):129053

H. Schneider, C. Albrecht, MS. Ahmed, M. Broekhuizen, L. Aengenheister, T. Buerki-Thurnherr, AHJ. Danser, S. Gil, SR. Hansson, R. Greupink, RM. Lewis, UR. Markert, L. Mathiesen, N. Powles-Glover, C. Wadsack, P. Brownbill. (2022). Ex vivo dual perfusion of an isolated human placenta cotyledon: towards protocol standardization and improved inter-centre comparability. Placenta, 2022 Aug:126:83-89

CW. Lederer, L. Koniali, T. Buerki-Thurnherr, PL. Papasayva, S. La Grutta, A. Licari, F. Staud, D. Bonifazi, M. Kleanthous. (2022). Catching them early: Framework parameters and progress for prenatal and childhood applicatoin of advanced therapies. Pharmaceutics 2022, 14(4), 793

A. Boos, PM. Misun, G. Brunoldi, LA. Furer, L. Aengenheister, M. Modena, N. Rousset, T. Buerki-Thurnherr, A. Hierlemann. (2021). Microfluidic co-culture platform to recapitulate the maternal-placental-embryonic axis. Advanced Biology. DOI: 10.1002/adbi.202100609.

E. Bongaerts, L. Aengenheister, BB. Dugershaw. P. Manser. MBJ. Roeffaers, M. Ameloot, TS. Nawrot, H. Bové, T. Buerki-Thurnherr (2021). Label-free detection of uptake, accumulation and translocation of diesel exhaust particles in ex vivo perfused human placenta. J Nanobiotechnol (2021) 9:144.

L. Mathiesen, T. Buerki-Thurnherr, J. Pastuschek, L. Aengenheister, LE. Knudsen. (2021). Fetal exposure to environmental chemicals; insights from placental perfusion studies. Placenta, DOI: 10.1016/j.placenta.2021.01.025.

L. Aengenheister, RR. Favaro, DM. Morales-Prieto, LA. Furer, M. Gruber, C. Wadsack, UR. Markert, T. Buerki-Thurnherr. (2021). Reserach on nanoparticles in human perfused placenta: state of the art and perspectives. Placenta, 104, 199-207.

C. Hempt, C. Hirsch, Y. Hannig, A. Rippl, P. Wick, T. Buerki-Thurnherr. (2021). Investigating the effects of differently produced synthetic amorphous silica (E551) on the integrity and functionality of the human intestinal barrier using an advanced in vitro co-culture model. Arch Toxicol, DOI: 0.1007/s00204-020-02957-2.

BB. Dugershaw, L. Aengenheister, S. Schmidt Kjolner Hansen, K. Sorig Hougaard, T. Buerki-Thurnherr. (2020). Recent insights on indirect mechanisms in developmental toxicity of nanomaterials. Part Fibre Toxicol., 17, 31 (2020).

W. Netkueakul, D. Korejwo, T. Hammer, S. Chortarea, P. Rupper, O. Braun, M. Calame, B. Rothen-Rutishauser, T. Buerki-Thurnherr, P. Wick, J. Wang. (2020). Release of graphene-related materials from epoxy-based composites: characterization, quantification and hazard assessment in vitro. Nanoscale, 2020,12,10703-10722.

C. Hempt, JP. Kaiser, O. Scholder, T. Buerki-Thurnherr, H. Hofmann, A. Rippl, TB. Schuster, P. Wick, C. Hirsch. (2020). The imapct of synthetic amorphouse silica (E551) on differentiated Caco-2 cells, a model for the human intestinal epithelium. Toxicol In Vitro. 28 May 2020, 67:104903.

B. Warth, K. Preindl, P. Manser, P. Wick, D. Marko, T. Buerki-Thurnherr (2019). Transfer and metabolism of the xenostrogen zearalenone in human perfused placenta. Environ Health Persp., 127(10):107004.

A.H.C. Anthis, E. Tsolaki, L. Didierlaurent, S. Staubli, R. Zboray, A. Neels, D. Dietrich, P. Manser, L.M. Desbiolles, S. Leschka, S. Wildermuth, S. Lehner, P. Chavatte-Palmer, W. Jochum, P. Wick, A, Dommann, T. Bürki-Turnherr, T. Fischer, R. Hornung, S. Bertazzo, I.K. Herrmann (2019) Nano-analytical Characterization of Endogenous Minerals in Healthy Placental Tissue: Mineral Distribution, Composition and Ultrastructure, Analyst, 2019, DOI:10.1039/C9AN01312A

L. Aengenheister, BB. Dugershaw, P. Manser, A. Wichser, R. Schoenenberger, P. Wick, M. Hesler, Y. Kohl, S. Straskraba, MJF. Suter, T. Buerki-Thurnherr (2019). Investigating the accumulation and translocation of titanium dioxide nanoparticles wiith different surface modifications in static and dynamic human placental transfer models. Eur J Pharm Biopharm. 142:488-497

M. Hesler, L. Aengenheister, B. Ellinger, R. Drexel, S. Straskraba, C. Jost, S. Wagner, F. Meier, H. von Briesen, C. Büchel, P. Wick, T. Buerki-Thurnherr, Y. Kohl (2019). Multi-endpoint toxicological assessment of polystyrene nano- and microparticles in different biological models in vitro. Toxicol In Vitro. 2019 Jul 27;61:104610. DOI: 10.1016/j.tiv.2019.104610

B. Fadeel, C. Bussy, S. Merino, E. Vázquez, E. Flahaut, F. Mouchet, L. Evairste, L. Gauthier, J. Koivisto, U. Vogel, C. Martín, LG. Delogu, T. Buerki-Thurnherr, P. Wick, D. Beloin-Saint-Pierre, R. Hischier, M. Pelin, CF. Carniel, M. Tretiach, F. Cesca, F. Benfenati, D. Scaini, L. Ballerini, K. Kostarelos, M. Prato, A. Bianco (2018). Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment. ACS Nano DOI: 10.1021/acsnano.8b04758  

L. Aengenheister, D. Dietrich, A. Sadeghpour, P. Manser, L. Diener, A. Wichser, U. Karst, P. Wick, T. Buerki-Thurnherr (2018). Gold nanoparticle distribution in advanced in vitro and ex vivo human placental barrier models. J Nanobiotechnol (2018) 16:79.

T. Buerki-Thurnherr, K. Schaepper, L. Aengenheister, P. Wick (2018). Developmental toxicity of nanomaterials: Need for a better understanding of indirect effects. Chem. Res. Tox. 2018, 31 (8), 641-642.

T. Notter, L. Aengenheister, U. Stadlbauer-Weber, P. Wick, U. Meyer, T. Buerki-Thurnherr (2018). Prenatal exposure to TiO2 nanoparticles causes behavioral deficits relevant for autism-spectrum disorders and beyond. Transl. Psychiatry 2018 Sep 20;8(1):193.

M. Kucki, L. Aengenheister, L. Diener, A. Rippl, S. Vranic, L. Newman, E. Vazquez, K. Kostarelos, P. Wick, T. Buerki-Thurnherr (2018). Assessment of cell viability and functionality of human placental trophoblast cells in vitro after exposure to label-free graphene oxide. 2D Mater. 5, 035014

L. Aengenheister, K. Keevend, C. Muoth, R. Schönenberger, L. Diener, P. Wick, T. Buerki-Thurnherr (2018). An advanced human in vitro co-culture model for translocation studies across the human placental barrier. Sci Rep. 2018; 8 (1):5388

B. Drasler, M. Kucki, F. Delhaes, T. Buerki-Thurnherr, D. Vanhecke, D. Korejwo, A. Petri-Fink, B. Rothen-Rutishauser, P. Wick (2018). Single exposure to aerosolized graphene oxide and graphene nanoplatelets did not initiate an acute biological response in a 3D human lung model. Carbon, 137, 125-135

J. Vidmar, T. Buerki-Thurnherr, K. Loeschner (2018). Use of alkaline or enzymatic sample pre-treatment prior to characterization of silver nanoparticles in human tissue by single particle ICP-MS. J. Anal. At. Spectrom. 2018, 33, 752

M. Kucki, L. Diener, N. Bohmer, C. Hirsch, H.F. Krug, V. Palermo, P. Wick (2017). Uptake of label-free graphene oxide by Caco-2 cells is dependent on the cell differentiation status. J Nanobiotechology, 2017 Jun 21;15(1):46. doi: 10.1186/s12951-017-0280-7.

S. Chortarea, H. Barosova, MJD. Clift, P. Wick, A. Petri-Fink, B. Rothen-Rutishauser (2017). Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than Healthy Cells. ACS Nano, 2017 May 23. doi: 10.1021/acsnano.7b01992.

C. Mouth, M. Grossgarten, U. Karst, J. A. Ruiz, D. Astruc, S. Moya, L. Diener, K. Grieder, A. Wichser, W. Jochum, P. Wick, T. Buerki-Thurnherr (2017). Impact of particle size and surface modification on the localization and penentration of gold nanoparticles in human placntal co-culture microtissues. Nanomedicine, 12(19), 1119-1133.

M. Kucki, P. Rupper, C. Sarrieu, M. Melucci, E. Treossi, A. Schwarz, V. León, A. Kraegeloh, E. Flahaut, E. Vázquez, V. Palermo, P. Wick  (2016) Interaction of graphene-related materials with human intestinal cells: an in vitro approach. Nanoscale, 8(16):8749-60.

C. Muoth, M. Rottmar, A. Schipanski, C. Gmuender, K. Maniura-Weber, P. Wick, T. Buerki-Thurnherr. (2016) A micropatterning approach to study the influence of actin cytoskeletal organization on polystyrene nanoparticle uptake by BeWo cells. RSC Advances, 6, 72827-72835.

C. Mouth, L. Aengenheister, M. Kucki, P. Wick, T. Buerki-Thurnherr (2016). Nanoparticle transport across the placental barrier: pushing the field forward! Nanomedicine, 11(8), 941-57. 

C. Muoth, A. Wichser, M. Monopoli, M. Correia, N. Ehrlich, K. Loeschner, A. Gallud, M. Kucki, L. Diener, P. Manser, W. Jochum, P. Wick, T. Buerki-Thurnherr (2016). A 3D co-culture microtissue model of the human placenta for nanotoxicity assessment. Nanoscale, 8, 17322-17332.

S. Grafmueller, P. Manser, L. Diener, L. Maurizi, PA. Diener, H. Hofmann, W. Jochum, H.F. Krug, T. Buerki-Thurnherr, U. von Mandach, P. Wick (2015). Transfer studies of polystyrene nanoparticles in the ex vivo human placenta perfusion model: key sources of artifacts. Sci. Technol. Adv. Mater. 16 (4) 044602.

S. Grafmueller, P. Manser, L. Diener, PA. Diener, X. Maeder-Althaus, L. Maurizi, W. Jochum, H.F. Krug, T. Buerki-Thurnherr, U. von Mandach, P. Wick (2015). Differential bidirectional transfer of polystyrene nanoparticles across the placental barrier reveals different transport kinetics. Environ Health Persp., 123(12), 1280-6.

S. Grafmueller, P. Manser, H.F. Krug, P. Wick, U. von Mandach (2013). Determination of the transport rate of xenobiotics and nanomaterials across the placenta using the ex vivo human placental perfusion model. J. Vis. Exp., (76), e50401, doi:10.3791/50401.

T. Buerki-Thurnherr, U. von Mandach, P. Wick (2012). Knocking at the door of the unborn child: Engineered nanoparticles at the human placenta barrier. Swiss Med Wkly., 2012;142:w13559.

P. Wick, A. Malek, P. Manser, D. Meili, X. Maeder-Althaus, L. Diener, PA. Diener, A. Zisch, H.F. Krug, U. von Mandach(2010). Barrier capacity of human placenta for nanosized materials. Environ Health Perspect., 118(3):432-6. Epub 2009 Nov 12.

P. Wick, A. E. Louw-Gaume, M. Kucki, H. F. Krug, K. Kostarelos, B. Fadeel, K. A. Dawson, A. Salvati, E. Vazquez, L. Ballerini, M. Tretiach, F. Benfenati, E. Flahaut, L. Gauthier, M. Prato, and A. Bianco (2014). Classification Framework for Graphene-Based Materials. Angewandte Chemie Int. Ed., 53, 7714 – 7718.



New positions

Congratulations!

Tuya and Lea succesfully defended their PhD's! Contgratulations!!!

 

 

 


Movie: Placenta perfusion @ Empa


Movie: See our contribution in NFP64 towards "Balancing Risks and Opportunities of Nanomaterials"