Bone atrophy and fractures, resulting from trauma, infections, osteoporosis, or cancer, are global health concerns. Standard care with cement and bone grafts has limitations. Synthetic polymers like polymethyl methacrylate risk leakage, spinal issues, and poor healing. Donor shortages for allogenic bone grafting and invasive procedures pose risks such as rejection and viral transmission. HYDROHEAL innovates with hydrogel formulations to address bone strength challenges by treating vertebral and alveolar fractures. HYDROHEAL aims to develop safe, sustainable scaling, and cost-effective formulations using renewable biomaterials for targeted drug delivery, aligning closely with the EU Circular Economy Action Plan and Chemicals Strategy for Sustainability. It is ready to introduce a new era in fracture therapy. The proposed self-solidifying hydrogels release active pharmaceutical ingredients locally upon external stimulation, potentially improving treatment efficacy, preventing infections, and speeding up fracture healing. The objectives of the project are: 1. Develop novel injectable hydrogel formulations combining natural substance derivates to enhance healing, inhibit bacterial growth, and monitor therapy progress in vivo. 2. Simultaneously manufacture carriers as micro- and nano-particles, surface-functionalized to incorporate pharmaceutical agents, releaseable upon external stimuli for tailored drug release. 3. Validate safe and optimized hydrogel formulations for treating vertebral and alveolar bone fractures through in vitro and in vivo tests. 4. Demonstrate scalable and sustainable biomaterial manufacturing through safe design methods, machine learning, and predictive life cycle assessment. 5. Develop machine learning and hybrid digital modeling methods, combining adaptive design of experiments and physics-based modeling with advanced characterization techniques.

Osteoporosis is a systemic, degenerative disorder, predominantly affecting postmenopausal women (1 out of 3) but also men at an advanced age (1 out of 5) and it increases the prevalence of fracture risk. One fifth of people suffering an osteoporotic fracture will die within a year and half will become dependent. Appropriate anti-osteoporotic drugs are available but have serious side effects and they do not promote fracture healing. The concept behind GIOTTO is to develop a platform of technologies and materials for the treatment of different types of osteoporotic fractures, designing, manufacturing and validating three different solutions: 1) 3D graded scaffold, which can be fixated with screws, to treat long bone fractures 2) Fibrous scaffold to deal with small, not confined pelvic fractures; 3) Radiopaque, bioresorbable, injectable cement to stabilise vertebral fractures. The three devices will share smart nanobiomaterials that release chemical and biological cues to stimulate bone regeneration while reducing bone loss. Nanofunctionalisation and the smart, temporalised release of active molecules will allow for the systematic cell recruitment and activation needed to face the challenges of stimulating bone tissue regeneration in the elderly. The use of additive manufacturing technologies will enable device personalisation to match and better align with the patient’s anatomy and fracture type. A further boost to meet patient specificity and needs, will be provided through the use of functionalised magnetic nanoparticles in order to provide, via the application of an external oscillating magnetic field, a remote tool to activate mechanotransduction. In parallel, an Internet of Things platform will be developed to gather and collate measurable data inputs about device effectiveness and to provide decision support software as a service to improve the design, manufacture and clinical function of the proposed devices, ultimately managing the overall value chain.

Improving the life quality of Europe’s increasingly elderly population is one of the most pressing challenges our society faces today. The need to treat age-related degenerative changes in e.g. articular joints or dental implants will boost the market opportunities for tissue regeneration products like biological scaffolds. State of the art 3D printing technologies can provide biocompatible implants with the right macroscopic shape to fit a patient-specific tissue defect. However, for a real functionality, there is a need for new biomaterials, technologies and processes that additionally allow the fabrication of a scaffold microstructure that induces tissue-specific regeneration. It is not possible to address the complexity in structure and properties of human tissues with a single material or fabrication technique. Besides, there are many types of tissue in the human body, each with their own internal structures and functions. INKplant vision is the fusion/combination of different biomaterials (6 different inks), high-resolution, high throughput additive manufacturing technologies already proved for industrial processes (ceramic sterolithography and 3D multimaterial inkjet printing), and advanced simulation and biological evaluation, to bring a new concept for the design and fabrication of biomimetic scaffolds (3D printed patient specific resorbable cell-free implants) which can address the complexity of the different tissue in the human body, demonstrated for 2 Use Cases. For a successful future translation, INKplant will consider all the relevant clinical adoption criteria already at the beginning of the development process. To address INKplant challenging objective the consortium includes the best expertise from the main areas of relevance to the project: biomaterials, 3D printing technology, tissue engineering, regulatory bodies and social humanities.

Nano-scaled materials are abundant in different stages of industrial manufacturing. Physical and chemical properties of these materials are strongly dependent on their size. Characterisation of mean size, size distribution, and shape of nano-scaled particles is very critical for the quality and efficiency of manufacturing processes. Yet, conventional characterisation technologies still show manifold shortcomings which represent a major innovation obstacle for manufacturers of nanoparticles. The NanoPAT consortium aims at closing this gap by the demonstration of 3 novel, real-time nano-characterisation Process Analytical Technologies (PAT), namely Photon Density Wave spectroscopy (PDW), OptoFluidic force induction (OF2i) and Turbidity spectrometry (TUS) including real-time data handling for digital process monitoring and product quality control. Those will be validated in 5 different industrial ceramic, polymer and mineral nanoparticles manufacturing and converting environments. This implies that innovating PATs will be paired with new data-analytical technologies in order to provide, for the first time, a real-time analysis for manufacturing processes of particles in the nanometer scale with sub minute temporal resolution. The NanoPAT consortium consists of 14 members, representing instrument developers, process data and modelling experts, academic process researchers, industrial processing experts, as well as innovation and dissemination specialists. The consortium profits from the broad involvement of its members in EU networks and ongoing H2020 projects. NanoPAT will intensively contribute to enhancing the innovation capacity of the European nanotechnology sector. As a result, the NanoPAT real-time nano-characterisation technologies will have reached TRL 6, promising valuable improvements in terms of quality, productivity and sustainability for the process industries in the EU and beyond.