Advancing bio-printing of living cells for regenerative medicine (HORIZON-HLTH-2027-03-TOOL-02)

Healthcare providers dispose of tools enabling them to treat conditions of unmet medical need. Individual patients will benefit from a personalised approach to their respective medical condition thanks to the bio-printed regenerative medicine solution. Scope: Tissue-specific functional 3D bio-printing of living cells has made significant progress as a new approach for transplantation applications in regenerative medicine. There are currently several types of bio-printing technologies under development for the repair of different targeted tissues or organs. To fully unleash the potential of bio-printed cell constructs for regenerative medicine several bottlenecks still need to be overcome. Various studies in pre-clinical models have shown that bio-printed cell constructs or tissues hold great promise for regenerative medicine, by allowing autologous tissue grafts being printed thus avoiding adverse graft-host reactions. However, translation of such approaches into clinical settings (i.e. humans) and their application to internal organs still needs to be investigated and demonstrated. Dependant on the actual target site (i.e. the defect tissue or organ in the human body) different bio-printing approaches may be preferable. For printing complex tissues and especially entire organs an in-vitro approach followed by transplantation is the preferred way. “In-situ” bio-printing, sometimes also referred to as “in-vivo”, or as “intraoperative”, reflects a bioprinting process performed on a live subject in a surgical setting and has in certain instances (e.g. tissue repair) advantages over an in-vitro bio-printing technique followed by transplantation. In-situ bio-printing involves direct patterning of bio-inks onto a patient’s body at the target site, allowing for precise construction of a site-matching tissue-structure within the actual physiological location where regeneration or repair is needed. As such, in-situ bio-printing allows for high adaptability, reduced risk of contamination, improved cell viability, function and host integration. The high cell densities present in the human vital organs underscore the importance of bio-inks which contain less additional biomaterials as matrix. Hence the bio-printing of cell constructs that comprise native tissue-like cell densities may facilitate repair and/or regeneration of defective complex tissues or internal organs. For such approaches meticulous engineering of the bio-printing equipment is necessary, involving sophisticated micro-surgical instrumentation and medical imaging platforms. To achieve the desired function and to mimic the natural cues in native tissues for in-vitro printed bio-constructs, the use of additional stimuli is needed, whereas in-situ approaches normally rely on the body as natural bioreactor providing the necessary extracellular cues. Recently, combinations of in-situ bio-printing with real-time stimuli have been investigated, even for the repair of internal organs. However, there remain bottlenecks that need to be overcome, like the integration with existing imaging modalities and surgical procedures or the long-time stability and functionality of the created bio-constructs. To address these challenges, researchers should work in multidisciplinary teams with engineers, biomedical scientists, cell biologists and medical doctors. Proposals should be based on the use of human cells and address all the following activities: Develop or improve existing bioprinting equipment that comprises all steps of the bio-printing suite to print bio-constructs with high cell-density for improved vascularisation and faster repair of the defect in the body. Scale-up the chosen bio-printing technology to a Good Manufacturing Practices (GMP) [1] conform/compliant manufacturing process. Perform all necessary regulatory work enabling the conduct of clinical studies and assess the clinical value of the developed bio-printing technology in first in-human studies. Priority should be given to bio-printing approaches that either target vital internal organs followed by surgical grafting or employ in-situ approaches depositing the cell-laden bioink directly from the printhead or endoscope on the defect target site in the body. Regulatory knowledge of the field is desired and should be documented through contacts with relevant national or international European regulatory authorities. A good understanding of the different steps involved and the inherent risks in each of these steps will be a basis to identify appropriate safety and quality requirements. Requirements from the different established EU frameworks on Substances of Human Origin (SoHO), medical devices and pharmaceuticals including Advanced Therapy Medicinal Products (ATMPs) should be considered for manufacturing/preparation as well as for clinical outcome monitoring. A combination of requirements from different frameworks might be most appropriate to allow for responsible and fast uptake. Proposals under this topic may address any therapeutic area, i.e. any disease, dysfunction or defect. Sex differences at the cellular level should be taken into consideration. Preclinical stage and clinical development are eligible. The involvement of small and medium-sized enterprises (SMEs) [2] is encouraged. The European Commission's Joint Research Centre (JRC) may contribute to the proposals selected for funding with work on strategic technologies for economic security and innovative industrial ecosystems, particularly activities on innovation in vitro biotechnologies. Applicants should provide details of their clinical studies [3] in the dedicated annex using the template provided in the submission system. As proposals under this topic are expected to include clinical studies, the use of the template is strongly encouraged. [1] https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en [2] https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32003H0361 [3] Please note that the definition of clinical studies (see introduction to this Work Programme part) is broad and it is recommended that you review it thoroughly before submitting your application.

Jogosultsági és benyújtási feltételek

"> General conditions 1. Admissibility Conditions, proposal page limit and layout Admissibility conditions are described in Annex A and Annex E of the Horizon Europe Work Programme General Annexes. Proposal page limits and layout are described in Part B of the Application Form available in the Submission System. 2. Eligible Countries Eligible countries are described in Annex B of the Work Programme General Annexes. A number of non-EU/non-Associated Countries that are not automatically eligible for funding have made specific provisions for making funding available for their participants in Horizon Europe projects. See the information in the Horizon Europe Programme Guide . 3. Other Eligibility Conditions In recognition of the opening of the US National Institutes of Health’s programmes to European researchers, any legal entity established in the United States of America is eligible to receive Union funding. If projects use satellite-based earth observation, positioning, navigation and/or related timing data and services, beneficiaries must make use of Copernicus and/or Galileo/EGNOS (other data and services may additionally be used). The Joint Research Centre (JRC) may participate as member of the consortium selected for funding as a beneficiary with zero funding, or as an associated partner. The JRC will not participate in the preparation and submission of the proposal - see General Annex B. Other eligibility conditions are described in Annex B of the Work Programme General Annexes. 4. Financial and operational capacity and exclusion Financial and operational capacity and exclusion are described in Annex C of the Work Programme General Annexes. 5a. Evaluation and award: Award criteria, scoring and thresholds Award criteria, scoring and thresholds are described in Annex D of the Work Programme General Annexes. 5b. Evaluation and award: Submission and evaluation processes The thresholds for each criterion will be 4 (Excellence), 4 (Impact) and 4 (Implementation). The cumulative threshold will be 12. Submission and evaluation processes are described in Annex F of the Work Programme General Annexes and the Online Manual . 5c. Evaluation and award: Indicative timeline for evaluation and grant agreement Indicative timeline for evaluation and grant agreement are described in Annex F of the Work Programme General Annexes. 6. Legal and financial set-up of the grants The granting authority may, up to 4 years after the end of the action, object to a transfer of ownership or to the exclusive licensing of results, as set out in the specific provision of Annex 5. Legal and financial set-up of the grants are described in Annex G of the Work Programme General Annexes. Specific conditions Specific conditions are described in the specific topic of the Work Programme. Application and evaluation forms and additional documents: Application and evaluation form templates Standard application form (HE RIA, IA) - the application form specific to this call is available in the Submission System Standard evaluation form (HE RIA, IA) - will be used with the necessary adaptations Guidance HE Programme Guide Model Grant Agreement (MGA) HE MGA Call-specific instructions Information on clinical studies (HE) Additional documents HE Main Work Programme 2026-2027 – 1. General Introduction HE Main Work Programme 2026-2027 – 4. Health HE Main Work Programme 2026-2027 – 15. General Annexes HE Programme Guide HE Framework Programme 2021/695 HE Specific Programme Decision 2021/764 EU Financial Regulation 2024/2509 Decision authorising the use of lump sum contributions under the Horizon Europe Programme Rules for Legal Entity Validation, LEAR Appointment and Financial Capacity Assessment EU Grants AGA — Annotated Model Grant Agreement Funding & Tenders Portal Online Manual Funding & Tenders Portal Terms and Conditions Funding & Tenders Portal Privacy Statement

Programkörnyezet

Topics under this destination are directed towards the Key Strategic Orientation 2 “ The Digital Transition ” and Key Strategic Orientation 3 “ A More Resilient, Competitive, Inclusive, and Democratic Europe ” of Horizon Europe’s strategic plan 2025-2027 [1] . Research and Innovation supported under this destination should contribute to the following expected impact, set out in the strategic plan impact summary for the Health Cluster: “ Health technologies, data, new tools, and digital solutions are applied effectively thanks to their inclusive, ethically sound, secure and sustainable delivery, integration and deployment in health policies and in health and care systems. ” The Health Cluster will continue to drive the development and adoption of innovative technologies and digital solutions to improve healthcare and health systems. This will ensure that the EU remains at the forefront of breakthrough health and medical technologies and can achieve open strategic autonomy in essential medical supplies and digital innovations. In line with the Commission's Political Guidelines for 2024-2029 [2] , this destination will support research and innovation in tools and technologies strengthening the competitiveness of European health industry and reinforcing EU autonomy. This effort will contribute to the completion of the European Health Union which aims to enhance the resilience of healthcare systems, facilitate access to innovative and affordable healthcare solutions, and ensure that all citizens have access to high-quality, equitable, inclusive and sustainable healthcare. The development and use of innovative tools and technologies for biomedical research are the basis for prevention, early diagnosis, efficacious therapy and patient monitoring, essential components of efficient healthcare. These include enabling technologies, not least innovative biotechnological approaches, and emerging technologies like synthetic biology, digital tools including those based on Machine-Learning/Artificial Intelligence (ML/AI) and other data-driven approaches which will enable the development of more personalised medicine. Hence the combination of innovative tools, high-quality health data (incl. Real-World Data - RWD [3] ), digital technologies, modelling and AI tools holds great potential not only for advancing biomedical Research and Innovation but for developing health technologies that improve healthcare. However, the implementation of these tools and technologies faces specific barriers such as scalability, regulatory frameworks and public acceptance and trust. To overcome these challenges cross-sectoral cooperation among stakeholders including researchers, regulatory bodies, policymakers, industry, healthcare providers and patients, is necessary. This collaboration will facilitate the design and development of innovative health products and services, tailored to specific population groups, ultimately improving patient outcomes and reducing health inequalities. By taking a comprehensive and inclusive approach, this destination will prioritise the development of novel tools and technologies that address key considerations such as the rights of the individual, safety, effectiveness, appropriateness, accessibility, comparative value-added and fiscal sustainability while also ensuring ethical, legal and regulatory compliance. In this Work Programme part, Destination “ Developing and using new tools, technologies and digital solutions for a healthy society ” is driven mainly by three key Commission policies, the “Biotechnology and Biomanufacturing Communication” [4] the “Artificial Intelligence Strategy” [5] and the “Strategy for European Life Sciences” [6] and focuses on developing and applying innovative technologies to improve human health and healthcare systems. The topics under this destination cover efforts to develop AI based predictive biomarkers for disease prognosis and treatment response, advancing bio-printing of living cells for regenerative medicine, and integrating New Approach Methodologies (NAMs) to advance biomedical research, as well as developing virtual human twins for integrated clinical decision support. To increase the impact of EU investments under Horizon Europe, the Commission encourages cooperation between EU-funded projects to enable cross-fertilisation and other synergies. For example, this cooperation could take the form of networking, to joint activities, such as the participation in joint workshops, exchange of knowledge, development and adoption of best practices, or joint communication activities. Opportunities for such activities and potential synergies exist between projects funded under the same topic but also between other projects funded under different topics, Clusters or Pillars of Horizon Europe. Specifically, this could involve projects related to European health research infrastructures (under Pillar I of Horizon Europe), the EIC [7] strategic challenges on health (under Pillar III of Horizon Europe) or with projects on themes that cut across the Clusters of Pillar II such as with Cluster “Digital, Industry and Space” on digitalisation of the health sector or key enabling technologies. Expected Impacts : Proposals for topics under this destination should set out a credible pathway towards the development and use of new tools, technologies and digital solutions for a healthy society, and more specifically to one or several of the following impacts: Europe’s scientific and technological expertise and know-how, its capabilities for innovation in new tools, technologies and digital solutions, and its ability to take-up, scale-up and integrate innovation in healthcare is world-class. Citizens benefit from targeted and faster research resulting in safer, more sustainable, efficient, cost-effective, accessible and affordable tools, technologies and digital solutions for improved (personalised) disease prevention, diagnosis, treatment and monitoring for better patient outcome and wellbeing, in particular through increasingly shared health resources (interoperable data, infrastructure, expertise, citizen/patient driven co-creation) [8] . The EU gains high visibility and leadership in terms of health technology development, including through international cooperation. The burden of diseases in the EU and worldwide is reduced through the development and integration of innovative diagnostic and therapeutic approaches, personalised medicine approaches, digital and other people-centred solutions for healthcare. Both the productivity of health Research and Innovation, and the quality and outcome of healthcare is improved thanks to the use of health data and innovative analytical tools, such as AI supported decision-making, in a secure, ethical and inclusive manner, respecting individual integrity and underpinned with public acceptance and trust. Citizens trust and support the opportunities offered by innovative technologies for healthcare, based on expected health outcomes and potential risks involved. Legal entities established in China are not eligible to participate in both Research and Innovation Actions (RIAs) and Innovation Actions (IAs) falling under this destination. For additional information please see “Restrictions on the participation of legal entities established in China” found in the Annex B of the General Annexes of this Work Programme. The protection of European communication networks has been identified as an important security interest of the Union and its Member States. Entities that are assessed as high-risk suppliers [9] of mobile network communication equipment (and any entities they own or control) are not eligible to participate as beneficiaries, affiliated entities and associated partners to topics identified as “subject to restrictions for the protection of European communication networks”. Please refer to the Annex B of the General Annexes of this Work Programme for further details. [1] https://research-and-innovation.ec.europa.eu/funding/funding-opportunities/funding-programmes-and-open-calls/horizon-europe/strategic-plan_en [2] https://commission.europa.eu/about/commission-2024-2029_en [3] EMA definition: “Real-World Data are routinely collected data relating to patient health status or the delivery of healthcare from a variety of sources other than traditional clinical trials (e.g. claims databases, hospital data, electronic health records, registries, mhealth data, etc.)”. [4] Commission Communication on Building the future with nature: Boosting Biotechnology and Biomanufacturing in the EU; COM(2024) 137 final: https://research-and-innovation.ec.europa.eu/document/download/47554adc-dffc-411b-8cd6-b52417514cb3_en [5] Commission Communication on Artificial Intelligence for Europe; COM(2018) 237 final: https://digital-strategy.ec.europa.eu/en/policies/european-approach-artificial-intelligence ; https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=COM:2018:237:FIN [6] https://research-and-innovation.ec.europa.eu/strategy/strategy-research-and-innovation/jobs-and-economy/towards-strategy-european-life-sciences_en ; https://ec.europa.eu/commission/presscorner/detail/en/ip_25_1686 [7] https://eic.ec.europa.eu [8] Commission Communication on the digital transformation of health and care; COM(2018) 233 final [9] Entities assessed as “high-risk suppliers”, are currently set out in the second report on Member States’ progress in implementing the EU toolbox on 5G cybersecurity of 2023 (NIS Cooperation Group, Second report on Member States’ progress in implementing the EU Toolbox on 5G Cybersecurity, June 2023) and the related Communication on the implementation of the 5G cybersecurity toolbox of 2023 (Communication from the Commission: Implementation of the 5G cybersecurity Toolbox, Brussels, 15.6.2023 C(2023) 4049 final).

Hivatkozott dokumentumok

Annex A Horizon Europe Programme Guide Online Manual Standard application form (HE RIA, IA) Standard evaluation form (HE RIA, IA) HE MGA Information on clinical studies (HE) HE Main Work Programme 2026-2027 – 1. General Introduction HE Main Work Programme 2026-2027 – 4. Health Decision authorising the use of lump sum contributions under the Horizon Europe Programme Rules for Legal Entity Validation, LEAR Appointment and Financial Capacity Assessment EU Grants AGA — Annotated Model Grant Agreement Funding & Tenders Portal Terms and Conditions