The epithelium is a cohesive two-dimensional layer of cells attached to a fluid-filled fibrous matrix, which lines most free surfaces and cavities of the body. It serves as a protective barrier with tunable permeability, which must retain integrity in a mechanically active environment. Paradoxically, it must also be malleable enough to self-heal and remodel into functional 3D structures such as villi in our guts or tubular networks. Intrigued by these conflicting material properties, the main idea of this proposal is to view epithelial monolayers as living engineering materials. Unlike lipid bilayers or hydrogels, widely used in biotechnology, cultured epithelia are only starting to be integrated in organ-on-chip microdevices. As for any complex inert material, this program requires a fundamental understanding of the structure-property relationships. (1) Regarding their effective in-plane rheology, at short time-scales epithelia exhibit solid-like behavior while at longer times they flow as a consequence of the only qualitatively understood dynamics of the cell-cell junctional network. (2) As for material failure, excessive tension can lead to epithelial fracture, but as we have recently shown, matrix poroelasticity can also cause hydraulic fracture under stretch. However, it is largely unknown how adhesion molecules, membrane, cytoskeleton and matrix interact to give epithelia their robust and flaw-tolerant resilience. (3) Regarding shaping 3D epithelial structures, besides the classical view of chemical patterning, mechanical buckling is emerging as a major morphogenetic driving force, suggesting that it may be possible design 3D epithelial structures in vitro by mechanical self-assembly. Towards understanding (1,2,3), we will combine a broad range of theoretical, computational and experimental methods. Besides providing fundamental mechanobiological understanding, this project will provide a framework to manipulate epithelia in bioinspired technologies.
Computing systems are ubiquitous in our daily life and have transformed the way we learn, work, or communicate with each other, to the point that progress is intimately tied to the improvements brought by new generations of the processors that lie at the heart of these systems. A common trait of current computing systems is that their internal data communication has become a fundamental bottleneck. The anticipated death of Moore’s Law has forced computer scientists and architects to find new ways to build faster processors, which include massive parallelization, specialized accelerator design, and disruptive technologies such as quantum computing. These trends cause an exponential increase in the volume and variability of data transfers within computing systems, rendering traditional interconnects insufficient and threatening to halt progress unless fast and versatile communication alternatives are developed. In this context, the WINC project envisions a revolution in computer architecture enabled by the integration of wireless networks within computing systems. The main hypothesis is that wireless terahertz technology will lead to at least a tenfold improvement in the speed, efficiency, and scalability of both non-quantum and quantum systems. With a cross-cutting approach, WINC aims to validate the hypothesis by (i) revealing the fundamental limits of wireless communications within computing packages, (ii) developing antennas and protocols that operate close to those limits while complying with the stringent constraints of the scenario, and (iii) developing radically novel architectures that translate the unique benefits of the wireless vision into order-of-magnitude improvements at the system level. If successful, WINC will be the seed of a new generation of non-quantum and quantum systems and foster progress in the computing field for the decades to come.
The main goal of NAVSCIN is to develop an improved strategy to mitigate scintillation –a particular type of space weather perturbation– tailored for satellite-based navigation techniques, in close collaboration with users and manufacturers of these technologies. Indeed, once the scintillation effect is correctly detected and mitigated, the availability and accuracy of the five billion devices using Global Navigation Satellite Systems around the world, will dramatically improve. The project implements a set of coordinated actions among its different partners that maximize international collaboration between universities, research centres and industry, in different European and Asian countries: First, NAVSCIN will improve the understanding regarding the physical processes resulting in the formation of scintillation, and consequently to identify the drivers in the interplanetary medium, the magnetosphere and the atmosphere. Second, the impact of scintillation on space-based navigation users will be characterised: mainly Ground and Aircraft Based Augmentation Systems (SBAS, GBAS) and high-accuracy navigation techniques (Precise Point Positioning). Third, a set of NAVSCIN algorithms will be developed suitable to support, for the first time, the real-time identification, correction and/or mitigation of scintillation in GNSS receivers. Finally, NAVSCIN will work systematically with potential users to assess the functionality, reliability and efficiency of the proposed solution, paving the way to its systematic exploitation and to its sustainable operation. Overall, the European competitiveness will be potentiated throughout the project with the exploitation of the research results, ultimately giving high-level EU employment and maintaining the European status quo of high‐level‐knowledge countries.
Improving the survival of patients with osteosarcoma has long proved challenging. Osteosarcoma is a rare bone cancer (less than 0.2% of all cancers). However, it affects mainly children and young adolescents. The standard therapy for osteosarcoma consists in the surgeon removing the entire tumor with negative margins (resection of larger areas of bone than the tumor itself), to ensure that no cancer cells are found at the edge of the tissue removed. This means that in some cases these surgeries associate limb amputation and even when it is not the case, most patients that undergo limb-sparing surgery need reconstructive surgery to regain limb function. The aim of TRANSFORMER is to bring closer to the market a solution that will allow to simultaneously treat bone cancer in absence of side effects while allowing bone regeneration. The product to be developed in TRANSFORMER puts together for the first time bone regeneration biomaterials with an innovative therapy for cancer that – in contrast to chemotherapy – up to now has shown no secondary effects: cold atmospheric plasma-treated hydrogels. The technology is protected by two PCT. TRANSFORMER value proposition: the product focused in in TRANSFORMER will have a double advantage for the patients and clinicians: it will be a local therapy that will allow simultaneous bone cancer treatment and bone regeneration. TRANSFORMER is structured along several objectives: (i) to preclinically validate the plasma-treated biocomposite as a potential therapy against bone cancer and towards bone regeneration, advancing the technology from TRL of 3 to 5, subsequently making it ready for clinical development and transfer to a spin-off or a third party company. (ii) To consolidate our IP position. (iii) To adapt the development roadmap to the regulatory requirements. (iv) To build a comprehensive business case for the exploitation of the technology and subsequent strategy for knowledge transfer.
Bacterial bone infections are one of the great challenges of orthopaedic and maxillofacial surgery, aggravated by antibiotic resistance, a serious health threat responsible for 700,000 deaths per year. The recent discovery of the bactericidal properties of some naturally occurring surface topographies has opened a new avenue of research. However, there is incomplete knowledge of the mechanisms of action and too many unanswered questions to translate these advances into clinical use. BAMBBI aims to tackle this challenge by developing synthetic bone grafts featuring contact-based antimicrobial properties, adding antimicrobial activity to their capacity to support bone regeneration. Using a novel bottom-up approach inspired in biomineralization routes, I intend to engineer the surface of calcium phosphates with an unprecedented and fine control of nanotopography by harnessing the power of ions and organic molecules (e.g. amino acids, calcium chelators and surfactants) to drive crystal nucleation and growth. Moreover, we will further enhance the antimicrobial effect by exploiting the synergy with chemical moieties to modulate bacterial affinity for the surface and/or confer additional antimicrobial properties by immobilisation of antimicrobial peptides. This will provide us with a platform to study the contact-based bactericidal mechanisms in depth and unravel the role of nanotopography and surface chemistry and their interplay with the intrinsic properties of bacteria. Only considering all these parameters will it be possible to unveil the causes of the substantial differences in bactericidal efficacy of a given substrate for different bacteria and design more efficient antibacterial surfaces. In addition to being a major breakthrough in the field of bone regeneration, the progress in new methods of fine-tuning the nanostructure of calcium phosphates will have an impact in very diverse fields such as catalysis, water purification and protein separation.