New Paper Published on the Perspectives for Future Use of Cardiac Microtissues from Human Pluripotent Stem Cells

Our project partners from the Leiden University Medical Centre (LUMC) have published a paper on the “Perspectives for Future Use of Cardiac Microtissues from Human Pluripotent Stem Cells”.

Organ-on-chip technology based on microfluidic devices has recently been combined with stem cell-derived organoids and microtissues to create vascularized structures that can be subjected to fluidic flow and to which immune cells can be added to mimic inflammation of tissue postinjury. Similarly, the integration of nerve cells in these models can provide insight into how the cardiac nervous system affects heart pathology, e. g. after myocardial infarction. This article summarizes various 3D microphysiological systems that have been used to model human heart tissue, including cell sources, applications, and readouts and considers these models and approaches in the context of cardiovascular disease. The authors reflect on perspectives for their future implementation in understanding disease mechanisms and the drug discovery pipeline. Read more here.

New Paper on “In-Line Analysis of Organ-on-Chip Systems with Sensors: Integration, Fabrication, Challenges, and Potential” published

Organ-on-chip systems are promising new in vitro research tools in medical, pharmaceutical, and biological research. Their main benefit, compared to standard cell culture platforms, lies in the improved in vivo resemblance of the cell culture environment. A critical aspect of these systems is the ability to monitor both the cell culture conditions and biological responses of the cultured cells, such as proliferation and differentiation rates, release of signaling molecules, and metabolic activity. Today, this is mostly done using microscopy techniques and off-chip analytical techniques and assays. Integrating in situ analysis methods on-chip enables improved time resolution, continuous measurements, and a faster read-out; hence, more information can be obtained from the developed organ and disease models. Integrated electrical, electrochemical, and optical sensors have been developed and used for chemical analysis in lab-on-a-chip systems for many years, and recently some of these sensing principles have started to find use in organ-on-chip systems as well.

This perspective review describes the basic sensing principles, sensor fabrication, and sensor integration in organ-on-chip systems. The review also presents the current state of the art of integrated sensors and discusses future potential. We bring a technological perspective, with the aim of introducing in-line sensing and its promise to advance organ-on-chip systems and the challenges that lie in the integration to researchers without expertise in sensor technology.

You can access the full review here.

EUROoC M38 Meeting and Career Coaching Sessions

On 24 and 25 January 2022, the EUROoC-ITN met again for the biannual consortium meeting. The ESRs presented their progress and explained what the last few steps of their project would be. They also presented how collaborations with each other enabled better development of their systems.

With the end of their projects approaching, they had the chance to learn more about the different career paths available to them thanks to Q&A sessions with professionals from regulatory agencies (Frank Schulze from BfR and Susanne Brendler-Schwaab from BfArM), technology developing industries (Roland Thar from PyroScience) and pharmaceutical industries (Stefan Kauschke from Boehringer Ingelheim, Jean-Marc Balloul and Cecile Zaupa from Transgene, Christian Egler-Wedeking from Miltenyi).
They learnt what each different career path entails, from the demands and requirements, as well as benefits of each role. We hope that the session could help them in choosing the career path that best fits their goals.

Validation Workshop Successfully Completed

The EUROoC validation workshop took place virtually from 17 to 19 January 2002. The focus of the workshop was to provide insights into the structure and functions of the main European regulatory agencies like Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), Bundesinstitut für Risikobewertung (BfR), Rijksinstituut voor Volksgezondheid en Milieu (RIVM) and Medicines Evaluation Board (CBG-MEB).

The ESRs learnt about the processes for the assessment of human medicinal products, chemicals and oncology products within the European regulatory network. Particular importance was given to the aspects of drug metabolism and drug-drug interaction when investigating compounds. Moreover, they were offered an overview of the validation processes for in-vitro models, animal models and examples of validation of microphysiological systems.

The workshop was concluded with the validation procedure for vaccines and an intro to the Inno4Vac project which has the objective to validate organ-on-chip models for the testing of vaccines at the early developmental stage, a very relevant topic of today.

Workshop in Microfabrication and Scientific Communication

On 16-17 September the EUROoC ESRs were welcomed to Uppsala for their second training workshop, focused on microfabrication and scientific dissemination. Given the pandemic, this was a mammoth task to organize with travel restrictions and group size restrictions. Fortunately, all the ESRs and two PIs were able to attend the worskshop which spanned over two days.

The topic of microfabrication was first introduced with a lecture from Lena Klintberg (lecturer within the Division of Microsystems Technology at Uppsala University), before practical exercises related to four different methods were carried out. The participants were then split into groups led by Gabriel, Mara, and Tanvi to learn about microfabrication in the cleanroom. The fabrication techniques the students learnt about was laser cutting, UV lithography and metal deposition and afterwards they were all trained in the art of bonding and assembly of microfluidic chips using either heat or plasma treatments. In fact, such was the level of expertise amongst the ESRs that some of them were even able to take on the role of teacher! In the end, all participants had a realistic view of working in a cleanroom, the advantages and limitations of each process and the ability to select a process specific to their application for their specific chip design.

The scientific dissemination topic was introduced by Sarah Schwarz, a senior lecturer at Uppsala University who specialises in academic English and oral presentations. This was followed by group work in which the ESRs prepared and presented on one of the above microfabrication techniques. Each group did an excellent job and received constructive and positive feedback on their presentations. There was just time for cake and bubbly at the end, where Gabriel (ESR 8), Stefanie (ESR 14) and Anders (ESR 15) could jointly celebrate the publication of their review article “In-line analysis of organ-on-chip systems with sensors: Integration, fabrication, challenges and potentials” recently published in ACS Biomaterials Science & Engineering before it was time for the ESRs to head off for the weekend.

In addition to the workshop, the ESRs explored Uppsala with a walking tour, and a ferry trip to the nearby islands. A huge thank you is due to the organisers who ensured an interesting and enjoyable itinerary, and the ESRs, for their positive attitudes and excellent cooperation. We are unsure about the future travel, but we look forward to seeing each other nevertheless!

ESR 15 – Secondment in Tubingen

During October and November 2021 I have been visiting NMI in Tübingen for a period of five weeks. The aim of the secondment was to learn about fabrication of microfluidic chips, and transfer a concept for a hydrogen peroxide sensor to microfluidics. I have felt very welcome at NMI by not only the two ESRs employed at NMI, but the entire working group and staff. In my spare time I have been sightseeing in both Tübingen and Stuttgart, hiking during sunny days (and one rainy), and went bouldering. All together with some of the cool people from the working group.

ESR 1 – Secondment in Lausanne

I am ESR1, Alessia Moruzzi, and I am working in the Micro-Organo Lab at NMI. My project focuses on the development of a Heart-on-chip platform. As one of the major milestones of the project is to integrate relevant hydrogels mimicking the human heartECM, I had the opportunity to gain more insight on the topic by joining the laboratory of Matthias Lütolf at EPFL in Switzerland from 7 June to 25 June. Here, I worked closely with Bilge Şen Elçi (ESR9) to screen for possible hydrogels to be loaded in the chip, which could ensure cardiac tissue viability and functionality. I also learned how to perform basic rheology measurements to characterize, viscosity, gelation time and stiffens of hydrogels. Coming from a purely biological background, I found extremely interesting learning more about the material properties of hydrogels and their characterization. During my stay, it was nice to see the contrast between Lausanne lively city centre, and the quiet periphery surrounding the University campus, with green fields and a panoramic view of the mountains. I also really liked the international atmosphere of EPFL. All the lab members were friendly and it was nice to join them in some after-work-get-togethers by the Geneva Lake or on campus. I look forward to visiting again and tasting more Fondue!

ESR10 – Secondment in Bern

My name is Merve Bulut (ESR10) and I am working at Leiden University Medical Center. My PhD project focuses on developing and validating a functional 3D vessel-on-chip platform that is highly representative of capillary and venule networks. Which be next used to model inflammatory responses of healthy and diseased human microvasculature in vitro using human induced pluripotent stem cell (hiPSC)-derived vascular cells. As a part of EUROoC-ITN, a secondment was planned in November 2020 at University of Bern in Prof. Dr. Olivier Guenat’s group for a training in 3D microvascular-on-chip model established in their group. Due to COVID19 restrictions in Europe, the training had to be carried out remotely. The PDMS-based microfluidic chips were kindly provided by Guenat’s group and shipped to us. The training for the microfluidic chip fabrication and 3D cell culture was successfully completed via video calls. During this period, the 3D cell culture protocol was slightly modified and optimized for hiPSC- derived vascular cells. Finally, we successfully established a perfusable 3D microvasculature network using hiPSC-derived endothelial cells together with hiPSC-derived vascular smooth muscle cells embedded in a fibrin gel. Using fluorescently tagged hiPSC lines, we could track cell-cell interaction and network development over time. The interconnected microvasculature network was stable at least for 10 days. At the end of this period, we concluded that the microvasculature model is very valuable to be integrated into our projects and be used for disease modelling. I am very grateful for the opportunity to collaborate with Guenat`s group. I would like to send special thanks to Dr. Sohelia Zeinali for the remote training and helpful discussions. Despite not being able to visit the lab in Bern and meet the group members in person, it was a very fruitful experience. We are looking forward to continuing our collaboration in this project!

EUROoCS 2021 Conference

The 3rd edition of the Annual European Organ-on-Chip Society (EUROoCS) Conference took place online, and was organised by Uppsala University. With 442 attendees from many different countries, there were even more participants than in 2020. In toal, 129 Posters and 40 talks were presented by experts and junior scientists. The talks were divided in 4 parallel sessions revolving around the topics of Vasculature, Disease Models, Technology Platforms, Toxicity, Respiratory System, Immune System, and Gastrointestinal Tract.
The ESRs of EUROoC actively participated in the conference by presenting their posters and talks. Moreover, Ulgu Arslan (ESR3) won the Best Presentation Award. We are looking forward to the next EUROoCS Conference, which will be held in person on 4 and 5 July 2022 in Grenoble, France.