SMART-ToC Tumor-on-Chip (ToC) platform incorporating Sensing hydrogel MAtrices

The aim of this WP is to develop SMART (Sensing hydrogel MAtrices correlating microenvironment and Response to immunoTherapy) hydrogels to incorporate in the breast cancer on chip platform. These matrices will possess fine-tunable properties (e.g., mechanical strength, cell-adhesion, degradability rate) and incorporate various sensors to map in real-time pH, oxygen tension, and mechanical forces in 3D. 

The aims of this WP are to develop the vascularized SMART-tumor on chip (ToC) model comprising a triple co-culture of breast cancer cells, cancer associated fibroblasts (CAFs), and immune cells (healthy tissue being a reference) in the SMART sensing matrices from WP1, to validate it with small chemotherapeutic agents, and to upgrade it for future large-scale production. 

The purpose of WP3 is to validate the SMART-ToC model from WP2 for its versatile use in therapy development. Specifically, we will demonstrate its utility for gaining insights into tolerability, therapeutic efficacy, and pharmacokinetics, for two approaches, antibody-drug conjugates (ADCs), and viral immunotherapies. 

In this WP, we will assess the societal and ethical readiness of SMART-ToC by applying a societal and ethical parallel trajectory (SEPT) with multiple interventions throughout the project. These activities aim to stimulate continuous reflection, create insights relevant for the design and development process of SMART-ToC, offer perspectives for future use and alternative applications, and inspire a culture of responsible and sustainable research and innovation 

The aims of this WP are to disseminate and communicate the project outcomes to a broad variety of audiences; to develop educational activities related to OoCs to train the new generation of scientists and to exploit SMART-ToC innovative technologies for future commercialization, by engaging with relevant stakeholders and end-users. 

UTwente | Le Gac’s lab: Applied Microfluidics for Bioengineering Research (AMBER)

Prof. Le Gac is chairing the Applied Microfluidics for Bioengineering Research group at the UT and has over 20 years’ experience in microfluidics and organ-on-chip technologies. She develops, with her team, innovative miniaturized devices for cancer research and reproductive medicine, and to evaluate the impact of plastics on human health. She has ample experience with industrial collaborations (e.g., OTP-NWO, TKI-LSH Health-Holland, Merck Serono, Hitachi), and technology transfer. She is the consortium coordinator and the main responsible for WP2. Within SMART-ToC, her team will develop the microfluidic platform, optimize cell patterning to create a vascularized tumor model, and conduct first-stage drug testing using chemotherapeutics.

Ali Al-Jaberi (PhD candidate) is a biomedical engineer with a background in Biotechnology for Health and Health Engineering from the University of Grenoble Alpes. During his Master's thesis, he participated in developing a vascularized renal proximal tubule-on-a-chip platform. His role in SMART-ToC is to develop a vascularized breast tumor model comprising a triple co-culture of breast cancer cells, cancer-associated fibroblasts (CAFs), and immune cells in tunable sensing matrices, and to validate the model for chemotherapy and immunotherapy applications.

Link to AMBER Research group webpage

UTwente | Paez lab

Dr. Paez is Associate Professor at the Developmental Bioengineering Group of the BioEngineering Technologies department at the UT and has expertise in synthetic macromolecular and biomaterials chemistry as well as soft matter applied to biomedicine. She started her independent career in 2019 as a Project Leader at INM—Leibniz Institute for New Materials in Germany and then joined the UT in 2021 as a tenure tracker. She has experience in collaborative projects with industry and in transfer of technology. She is the consortium co-coordinator and the main responsible for WP1. Within SMART-ToC, her team will develop the sensing hydrogel matrix with modulable properties to embed the tumor cells.

Dr. Minye Jin is a material scientist with a background in polymer science.  Within SMART-ToC, she developed soft matrices as 3D cell culture scaffolds for breast tumor model to validate its use for chemotherapy and immunotherapy applications. By varying the crosslinking chemistry and formulations, the resulting soft matrices exhibited tunable mechanical properties with sensing capabilities.

Link to Paez lab webpage

UniFri | Ruggi Group 

Dr. Ruggi is Senior Lecturer (Maître d'Enseignement et de Recherche) at the University of Fribourg (CH). He has extensive experience in photochemistry, including the design, synthesis, and photochemical evaluation of different classes of organic and inorganic compounds. He brings his expertise to WP1, developing the molecular sensors for oxygen and pH monitoring to functionalize the hydrogel matrices where the tumor will be embedded. 

Link to Ruggi Group webpage

RadboudUMC | Verdurmen Lab 

Dr. Verdurmen obtained his PhD cum laude at the Dept. of Biochemistry and is currently an Assistant Professor at the Dept. of Medical BioSciences, both at Radboudumc. After receiving a Rubicon grant (2012) to support his postdoctoral stay at the University of Zurich (CH), he received a prestigious Veni grant in 2015. Since 2016, with his group, he has been studying the efficacy of novel therapies and drug delivery mechanisms and kinetics in various models including (immunocompetent) OoC systems. His group’s work focusses on engineered antibodies and adenoviral therapies in application areas involving cancer, endometriosis, and fibrosis. He is the main responsible for WP2.  Within SMART-ToC, his team will test novel immunotherapies and validate the SMART-ToC device as screening device.

Saxion | Ethics & Technology group

Link to Ethics & Technology group

Saxion | Applied Nanotechnology group 

Aniek Welman is a researcher at the Research Group Applied Nanotechnology at Saxion University of Applied Sciences. Within the SMART-ToC project, she collaborates with colleagues from the Research Group Ethics & Technology to identify and explore the societal and ethical challenges associated with the development and application of SMART-ToC technology.

Link to Applied Nanotechnology group

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Proefdiervrij is a Dutch foundation committed to making the use of laboratory animals superfluous in scientific research. They focus on the prevention and replacement of laboratory animals in scientific research. Link to Proefdiervrij website

hDMT is the Institute for Human organ and Disease Model Technologies, comprising 16 partners including (technical) universities, university medical centers and knowledge institutes. Their mission is to facilitate and support the development of dynamic human models and their translation into practical applications for research, innovation, and a healthier future. Link to hDMT website