Lung disease is the third biggest cause of deaths globally. For the irreversible and terminal lung disease patients, lung transplantation is the only long-term therapy. Due to the unavailability the suitable donors, there is not only a minimum of 18 months of wait on the organ donation. Patients who eventually secure a lung transplant have less than 20% chance of recovery due to ‘poor organ function’. Therefore, there is not only a great need for an artificial lung as a permanent replacement organ but also as a bridge to transplantation. Existing artificial lung devices fail to mimic the flow gas exchange properties of a human lung and suffer from low biocompatibility, leading to undesired blood coagulation and hemolysis which limits their applicability to up to 30 days. The complexity and risk associated with current artificial lung technologies mean that they are not offered as long-term lung replacements or as a suitable bridge to transplantation. Through this 36 months EIC pathfinder project, the consortium led by Smart Reactors Ireland, aims to develop the world’s first biobased nanomaterial ‘nanocellulose’ to manufacture an artificial lung device used as a bridge to lung transplantation. The consortium will develop an initial proof of concept nanocellulose device to demonstrate gas transfer and initial hemocompatibility in blood. The proposed approach is expected to have two benefits, the first is that blood flow can occur in laminar flow conditions reducing haemolysis and damage to the blood. Secondly, nanocellulose, has the potential to be endothelialized which would allow for long term gas exchange without the need for systemic anticoagulants.

A major challenge facing Europe is its ageing population and associated increase in diagnosed cases of neurodegenerative diseases (NDD). Parkinson’s disease (PD) is associated with tremor and loss of motor functions due to progressive degeneration of dopaminergic neurons in the brain. This can lead to memory loss and dementia, which is associated with short- and long-term injuries and disabilities with emotional, financial, and social burdens for patients, families, and society. The exact causes and mechanisms underlying PD are still unknown and existing treatments focus on alleviating symptoms and increasing quality of life, but do not halt or reverse disease progression. Although animal models give unique possibilities to study physiological and behavioural mechanisms, drug development fails due to lack of translation to humans. Alternative non-animal NDD models is needed both in terms of better translation, but also to replace expensive and problematic animal experiments. We will move disease modelling to a new level and replace animal models, by creating a new concept we call connectoids. We will develop an ex-vivo-type in vitro human opto-electronic multi-regional brain-organoid disease model in which connectoids are formed by precise spatial arrangement of brain organoids connected via hydrogel tracts that promote axonal pathfinding, functional connection, and signalling. By developing 1) light controllable sub-type specific neurons within regionalized brain organoids, and 2) electrodes and waveguides that can penetrate the organoids able to monitor neurotransmitter signalling inside and between the organoids, we will for the first time be able to sense how a particular brain region responds to a certain therapy and watch in real time how signals are transmitted to other brain regions. Our model will not only have health benefit, but will relieve a heavy economic burden on society, and open up for new possibilities for technological and economic development.

We aim to transform virus biomanufacturing processes and enable new quality control strategies by a continuous, real-time capable biohybrid sensor technology to detect cell-based virus infection cycles. BioProS sensor concept makes use of an optical sensor technology in combination with cell-based measurement principles. In this context a platform technology will be developed that can be adapted to multiple specific analytes which enables its applicability in different industries and production settings. The development of such platform technology together with its technological complexity requires the involvement of multiple stakeholders throughout Europe and across disciplines (biology, engineering science, data science, manufacturing experts). Digitalisation has to extend from the very beginning of the process into the whole manufacturing chain, utilising all advances achieved in smart and lot-size-one manufacturing in recent years. This leads to the closely intertwined interaction of technical, informational and biological systems also referred to as bio-intelligent systems. This new paradigm opens up a large new space for innovations, recognised as a strategic field in America, Asia and Europe. Based on the manufacturing excellence leadership of Europe, BioProS will significantly contribute to all expected impacts of the Destination “Digital and Emerging Technologies” and explicitly to each of the four expected outcomes of this call topic. The consortium aims to gather all required expertise and set the basis for international partnerships. In close cooperation with pan-European initiatives and with the support of an industry advisory board, project partners aim to transform the vision of bio-intelligent manufacturing and demonstrate the applicability of disruptive technologies in an industrial setting. We will promote the research community for bio-intelligent methods and applications worldwide, and at the same time create technology sovereignty for Europe.

Tendinopathies and osteoarthritis (OA) are extremely common and these injuries associate with high health and socioeconomic costs, long-term postoperative rehabilitation, and loss of productivity. To date, none of the existing surgical or non-surgical alternatives have provided a successful long-term effect, and often the treated tissues do not restore their complete strength and functionality. To fill the critical gap of proper treatments TRiAnkle proposes to develop 3D bioprinted scaffolds based on collagen and gelatine, functionalised with stem cells and/or nanoencapsulated regenerative factors. The surgical implantation of these new functionalised biomaterials will enable the targeted delivery of the mentioned biologically active agents to promote cell growth and differentiation to enable better and faster regeneration of injured collagen-rich tissues like articular cartilage, ligament and tendon of the ankle. Two case-studies will be implemented: the partial rupture (>50%) of Achilles tendon and osteochondral cartilage injuries, which will serve as a technological platform to deliver new regenerative therapies for any other articular, tendinous or ligament diseases of weight-bearing joints. By achieving this goal, TRiAnkle will enable, in comparison with current surgical treatments: - To increase by 10-15% of the ankle joints functionality recovery ratios due to the presence of pro-regenerative components that promote the healing process decreasing also the risk of re-rupture or recidivation. - To reduce the recovery time and the associated healthcare costs up to 50% due to the use of scaffolds that mimic the natural structure and mechanical properties of joint tissues. TRiAnkle will be implemented by a multidisciplinary team made up of biomaterial production companies, manufacturing technologies experts, material engineers, preclinical validation centers, healthcare professionals, patients associations and experts in ethical, regulatory and exploitation.

Aim: The SILKink project aims to develop a breakthrough biocompatible hydrogel, i.e., a bioink, to 3D print bone marrow tissue models that can be used for robust culture of human stem cells. The use of silk as the basis for novel bioinks (SILKink) helps to recreate tailored bone marrow-like microenvironments that will enable new applications in drug development and personalized medicine for bone marrow diseases. Here, we aim to optimize and validate SILKink, further define the business opportunity, and found an investment-ready spin-off company to commercialize SILKink. Unmet need: Bone marrow stem cells are fragile and require highly specific surroundings to survive and differentiate, therefore the presence of a soft tissue environment mimicking the human bone marrow is critical for reproducible culturing of these cells. There is a large unmet need for reproducible solutions that mimic the soft tissue of the bone marrow to allow advancements in drug development and personalized medicine approaches for bone marrow diseases. Solution: We will develop SILKink: a revolutionary bioink that is uniquely based on silk to closely mimic the 3D soft tissue environment of the bone marrow. SILKink will provide a matrix that supports all bone marrow cells including hematopoietic stem and progenitor cells and allows to 3D print ex vivo bone marrow stem cell models in the shape or volume desired. Consortium: University of Pavia (UNIPV) and partner CELLINK have developed the SILKink prototype during FET Open project SilkFUSION and co-own the background IP. Partner Catalyze-Group – Venture Building Team (CAT) will bring commercial expertise to develop an optimal market access strategy for SILKink. UNIPV will be responsible for SILKink optimization, manufacturing, and validation. CELLINK will be involved in product optimization and responsible for product development. CAT will assist UNIPV with founding a spin-off company to commercialize SILKink and making it investment-ready.