Bioelectronic interfaces are machines designed to exchange information with living matter. They are opening new frontiers in medicine. For example, machines implanted in the body may soon enable repair of damaged tissues or replacement of functions affected by chronic disease. The realisation of this vision is impeded by the available hardware. Today’s materials, devices and systems are electronic, while soft living matter uses ions and molecules for communication and computation. The central hypothesis of GELECTRO is: electrically conductive hydrogels can enable bioelectronic machines that are multimodal and nearly indistinguishable from the biological host. The project will thus contribute a new class of interfacing technologies that are made almost entirely of water. If successful, they will not only blur the boundary with the host, but also tap into the control loops that organise and maintain the living system. The hypothesis will be validated by achieving five key aims. Hydrogels with dual (electronic and ionic) conductivity will be created by combining organic conductor and biomacromolecule building blocks. A tailored additive microfabrication method will be developed to combine hydrogels in devices. Devices that transduce electronic commands into ionic currents, release/sequestration of signalling molecules and mechanical actuation (and vice versa) will be constructed. Devices will be integrated in arrays and in circuits capable of sensing and actuation in aqueous environments. Finally, an impact case study interfacing GELECTRO machines with cortical organoid cultures will be developed. By emulating the finely tuned morphogens present in the early stages of brain development, GELECTRO machines will encode advanced tissue organisation and emergent electrical activity in the organoids. The project will catalyse interest in hydrogel-based electronics as a promising technology for next generation human-machine interfaces.

Biological vesicles hold great promise as nano compartments for various applications such as drug delivery systems, therapeutics, and diagnostic tools but fundamental relationships between material properties and activity are not sufficiently understood to create new products for the benefits of the European society. The overall aim of USOME is to develop characterization approaches for these novel materials enabling proper functionalisation. In particular, this proposal focuses on the development of an entirely novel analytical approach for the analysis of emerging biohybrid vesicles. As model systems we indicate polymersome-hybrids and exosome-hybrids, representing a variation in structure in terms of stability, origin (synthetic/natural) and their hybrid counterparts (proteins/synthetic polymers). Two processes will be studied in detail (i) the encapsulation of proteins in polymersomes; and (ii) the modification of exosomes with proteins and polymers. As a result, advanced analytical methods for characterization of polymersome and exosome hybrids for potential application in therapeutics and diagnostics will be established. The key to this envisaged breakthrough is based on field flow fractionation technique coupled to multiple detectors for elucidation of the structural and compositional distributions in the biohybid systems. This highly topical research will be performed within the individual fellowship of a young, very talented, and curiosity-driven African researcher in a leading European research institute. The combination of his expertise in analytical techniques, the biohybrids formation knowledge of IPF and specific knowledge of the associated partners will enable significant scientific progress in the field and unlocks value for patients. Excellent, customized training will open the ER the doors to a unique research profile, fully embedded in the international scientific community and with outstanding career chances at the fronteers of research.

This research addresses a clinical problem with an innovative approach. Pancreatic cancer is one of the deadliest cancers and only 10% of patients survive 5 years after diagnosis. To find better therapies, we need patient-specific models that mimic the biology of tumour tissues and target interactions between different cell types. We will develop a controllable platform for modelling the human disease in the laboratory. We will use our new platform to discover better ways of treating the disease.

My vision is to address a clinical problem with a novel and transformative approach. Using my unique expertise in cell biology, tissue engineering and translational research I will design technology platforms to test new treatments for human pancreatic cancer. Pancreatic tumours are cancers of unmet medical need with 85% of patients dying within 9 months of diagnosis. To find better therapies, we need patient-specific models that mimic the biology of tumour tissues and target interactions between malignant and non-malignant cells. Biomimetic tissue engineering is a powerful approach to generate 3D cancer models, however, only a few scientists use these technologies. Most 3D cultures of human cells include reconstituted matrices that originate from murine tumours containing undefined amounts of extracellular matrix and growth factors. There is no tissue-engineered 3D model that allows control over patient-specific and biomechanical characteristics of the pancreatic tumour microenvironment. I hypothesise that 3D approaches that replicate the native tissue composition and biomechanical properties will behave like real tumours to provide clinically predictive platforms and to test novel treatments that target both malignant and non-malignant cells. To test my hypothesis, I will: •3D-print matrix and cellular elements of the microenvironment of human pancreatic tumours •Develop a cancer-on-a-chip model of liver metastasis •Compare the crosstalk of malignant and other microenvironment components with the human disease •Validate my new platforms with treatments in clinical trials and test novel combination treatments that slow down or reduce tumour growth. In a multidisciplinary project, I will use: •3D printing to build platforms composed of hydrogels, fibrous scaffolds and patient-derived cells •Extracellular matrix molecules for chemical crosslinking into hydrogels •Cancer-on-a-chip models to study tumour metastasis •Imaging, biomechanical and multi-omics analyses.

New polymer materials are necessary to match the demand for highly integrated, multifunctional, responsive systems for sensing, information processing, soft robotics or multi-parametric implants. Both established material design concepts based on lithography, and emerging engineering efforts based on additive manufacturing (AM) are currently not able to fully address the need for topologically complex, multifunctional and stimuli-responsive polymer materials. This proposal aims at establishing a radically new approach for polymer material design, rethinking AM on both material and process level. Here, functionality will be already embedded at the building block level to emerge into larger scales. The exact methodology relies on polymer microparticles as a novel material basis with arbitrary geometry, function, mechanics and responsiveness. These microparticulate formulations will serve as predefined, voxel-like building blocks in AM yielding hierarchical assemblies with spatially defined voxel position and programmable, adaptive properties, which clearly go beyond existing functional material classes. With that, 3DPartForm will address the current lack of additive manufacturing providing multifunctional, stimuli-responsive materials, in which not only strongly different, but most importantly functional building blocks with intrinsic time axis will be processed into true 4D-polymer multimaterials. Products emerging from this approach will reach a previously unknown level of system integration, where optical transparency, electric and thermal conductivity as well as diffusivity and mechanical rigidity will become spatiotemporally tunable at single-voxel level. Coupled sensing and actuation operations will be realized by processing, transforming and manipulating single or combined input stimuli within these materials in the focus of 3DPartform, and platforms for biomimetics and cell-free biotechnology will be implemented as a long-term goal.