Periodic Reporting for period 1 - PHOENIX-OoC (Origami Paper-based tecHnology fOr the innovativE aNd sustaInable Organ-on-Chip devices)
Reporting period: 2024-03-01 to 2025-02-28
PHOENIX-OoC project aims to revolutionise Organ-on-a-Chip devices development, creating more affordable, sustainable, and accessible devices, wile maintaining the effectiveness and precision needed for biomedical research. Traditional Organ-on-a-Chip devices, while powerful tools for simulating organ-level functions and studying drug responses, often rely on complex fabrication processes and expensive materials, limiting their accessibility and scalability. PHOENIX-OoC introduces an innovative approach that leverages the unique physical and chemical properties of paper as the primary construction material. Paper’s flexibility, porosity, and biocompatibility make it an ideal platform for supporting cell growth and fluid transport. By employing origami-inspired configurations, the project enables the creation of intricate 3D microenvironments that can host co-cultures of cells, effectively mimicking the structural and functional complexity of human organ tissues. A key objective of the project is the integration of paper-based (bio)sensors to allow real-time monitoring of cellular activity and biochemical processes, providing high-resolution data for pharmacological and toxicological studies. Ultimately, the project seeks to deliver a new generation of Organ-on-a-Chip devices that are not only scientifically robust and precise but also affordable, eco-friendly, and widely accessible. This will open new possibilities for biomedical research, drug development, and personalized medicine, especially in resource-limited settings.
The achievements of WP1 encompass the successful design, fabrication, and validation of anisotropic cryogels tailored for biomimetic applications. The resulting cryogels exhibit permeability to liquids and tuneable pore architectures with (i) isotropic freezing producing randomly distributed pores, and (ii) anisotropic freezing generating vertically aligned pores that closely mimicked the native deep cartilage layer, confirmed by fluorescence imaging and SEM. The process demonstrates reproducibility across batches, with consistent pore alignment and mechanical stability. This advancement establishes a scalable framework for creating biomimetic scaffolds with application-specific pore orientation, offering significant potential for tissue engineering. From testing the cryogel in the first prototype of PHOENIX-OoC microfluidics, a new configuration is proposed and successively tested. Primary cells have successfully been isolated and tested on the anisotropic cryogels. Cell attachment studies demonstrate that chondrocytes adhered well to the scaffold surfaces, with no significant cytotoxicity. However, optimization studies are ongoing to achieve a more homogeneous distribution, preventing the formation of small clusters and ensuring uniform cell dispersion. The focus of WP2 is on microfluidic device construction and sensor development. Different microfluidic patterns are simulated, modelled and tested. Three sensors are developed and currently being optimized to evaluate their performances and working stability, to assess the feasibility for the challenging continuous measurement in a complex matrix and under flux, using different sensor modification depending on the analyte, and will then be included in the sensor array. The tested analytes are glucose, nitrate and pH, in standard solutions and in cell culture media. Results form WP3 deal with modelling for water and oxygen interaction with cellulose. Quantum-mechanical (QM) and atomistic dynamical simulations unravel details about the intra- and intermolecular interactions and their effects on adsorption, structure, energetics and stability. Computer simulations, data collection and data analytics are all essential ingredients in this endeavour to provide data of unrivalled detail and assist in the interpretation of experiments. At the same time, such simulations are challenging because of (i) the enormous complexity of paper-based materials and cellulose, (ii) the lack of detailed structural information available from experiments, (iii) the importance of considering dynamics and thermodynamics, and (iv) the long timescales needed for some processes to establish themselves (long from a modelling perspective). Water holds a special place for simulations of cellulose in the context of bio- and medical applications as water is omnipresent at ambient conditions and it is the most use solvent in analytical applications. Therefore, there is the need to provide for its presence and interaction competition with cellulose.
IBEC's cryogelation technique pioneered anisotropic cryogels fabrication with collagen-like pores, using sustainable cellulose-based materials for scalable, cost-effective production, while ensuring high cell viability, mechanical stability, and nutrient diffusion, with breakthroughs in cryopreservation enhancing long-term storage and regenerative therapy. UNIBAS demonstrated the cryogels scaffolds support high cell viability and attachment, having mechanical stability that matches native cartilage and enhanced nutrient diffusion making them suitable for physiologically relevant joint models. FTN's capillary-driven flow system eliminates external pumps, optimizing diagnostic test accuracy, reducing material waste, and enabling rapid design iterations with 3D-printed models, providing new knowledge in the field of applicable microfluidics based on paper, reducing the costs of manufacturing the complete microfluidic platform based on passive flow principles, and offering efficient microfluidic based complete organ-on-chip system useful for point-of-care concept for wider community. UNITOV has developed a paper-based electrochemical cell enabling reagent immobilization and analyte reactions with the working electrode, while overcoming limitations of traditional papers and promoting eco-friendly, scalable mass production. UU's research on oxygen and water interactions with cellulose pioneers the validation of xTB against PBE-D3 methods, enabling simulations of larger, more realistic systems, while using electronic and atomistic simulations to study molecular-level adsorption and interactions, producing unparalleled results and deciphering complex phenomena through tailored experiments, enhancing the understanding of cellulose-based materials for various applications in science and industry.