Periodic Reporting for period 1 - LIFESAVER (Living Impact on Fetal Evolution: Shelter-Analyze-Validate-Empower Regulations)
Période du rapport: 2021-11-01 au 2023-04-30
In Europe, about 75% of all neonatal deaths and 60% of all infant deaths occur in infants born preterm, and worldwide, 450 neonatal deaths occur every hour. The number of preterm births is growing despite advances in medicine as more pregnancies are at a later age, but also due to increasing environmental threats, use of medicines and lack of suitable treatments. The LIFESAVER project addresses the current unmet societal and healthcare needs in creating a sound and scientific knowledge base, which is needed to develop and implement regulatory approaches relevant to maternal and fetal health. It focuses on generation and validation of the data that would allow potential forecasting of effects of environmental pollutants and pharmaceutic treatments for pregnant women, which are usually very difficult to assess.
Premature births and neonatal health problems pose a severe and growing threat to the health and well-being of the future European population. The risks are not limited to the premature death of a baby but also may lead to severe complications in future life: the children can suffer from extra infection, poor vision, breathing problems, diabetes, hypertension, and increasing risks of cerebral palsy, bowel damage, stroke, and even lower IQ. This will affect their lives and significantly burden society over several generations. The LIFESAVER project addresses new opportunities in combined experimental and digital solutions for improving the healthcare and well-being of pregnant women which will be achieved with new biodigital twin in-vitro devices. It will also strengthen the competitiveness and growth of companies in environmental, medical and lab data analysis, bioprinting, tissue and cell engineering, and pharmacology.
The overall objective of LIFESAVER is to create and demonstrate a new, digitally cloned in vitro system for emulation of the prenatal conditions in the vicinity of the placental interface, capable of high biofidelity (= how well the artificial system can replicate the functionality of an organ or body rather than just mimicking its structure and anatomy), and corresponding risk predictions of a drug or a chemical substance as a potential harmful risk factor towards unborn babies, with all these features to be compatible and feasible for improvement of the respective regulations in Europe.
This research plan is built to achieve (i) conditions for a proper living environment for every pregnant woman, with minimal risks to the fetus, safeguarded with scientifically justified regulations of potentially harmful chemical and medicinal products; (ii) creation and demonstration of a new, digitally cloned in vitro system for emulating prenatal conditions occurring near the placental interface; (iii) ensuring a high biofidelity of this new system and provision of corresponding risk prediction of a drug or a chemical substance as a potentially harmful risk factor for unborn babies; (iv) provision of the added value (in the spirit of the Green Deal call) in scientifically-based tools for experimental screening, digital pre-screening, and analysis of chemicals and pharmaceuticals on their potential to cross placental tissue barriers.
Altogether this will provide a rationale for risk classification of existing and new compounds, as well as justifications of regulations and risk assessment/mitigation measures towards the potential effects of these compounds on pregnant women and fetal health.
The LIFESAVER project has the potential to contribute to several key EU strategies and offers a solution to several challenges highlighted by the European Commission. The project is in alignment with the objectives set in the European Green Deal (COM/2019/640 final), the recent EU Action Plan: 'Towards Zero Pollution for Air, Water and Soil’ (COM/2021/400 final) and the EU Chemicals Strategy for Sustainability (COM/2020/667 final). Indeed, by developing a new solution to determine and assess the impact of pollutants, chemicals and medicines on pregnant women and foetuses, the project is able to identify harmful components, and can hence contribute to the ability to better protect citizens and move towards a toxic-free environment. Finally, the project contributes to the Pharmaceutical Strategy for Europe (COM/2020/761 final), which, amongst others, underscores the lack of treatments for specific population groups such as pregnant women and urges for technological advances to address such issues.
Premature births and neonatal health problems pose a severe and growing threat to the health and well-being of the future European population. The risks are not limited to the premature death of a baby but also may lead to severe complications in future life: the children can suffer from extra infection, poor vision, breathing problems, diabetes, hypertension, and increasing risks of cerebral palsy, bowel damage, stroke, and even lower IQ. This will affect their lives and significantly burden society over several generations. The LIFESAVER project addresses new opportunities in combined experimental and digital solutions for improving the healthcare and well-being of pregnant women which will be achieved with new biodigital twin in-vitro devices. It will also strengthen the competitiveness and growth of companies in environmental, medical and lab data analysis, bioprinting, tissue and cell engineering, and pharmacology.
The overall objective of LIFESAVER is to create and demonstrate a new, digitally cloned in vitro system for emulation of the prenatal conditions in the vicinity of the placental interface, capable of high biofidelity (= how well the artificial system can replicate the functionality of an organ or body rather than just mimicking its structure and anatomy), and corresponding risk predictions of a drug or a chemical substance as a potential harmful risk factor towards unborn babies, with all these features to be compatible and feasible for improvement of the respective regulations in Europe.
This research plan is built to achieve (i) conditions for a proper living environment for every pregnant woman, with minimal risks to the fetus, safeguarded with scientifically justified regulations of potentially harmful chemical and medicinal products; (ii) creation and demonstration of a new, digitally cloned in vitro system for emulating prenatal conditions occurring near the placental interface; (iii) ensuring a high biofidelity of this new system and provision of corresponding risk prediction of a drug or a chemical substance as a potentially harmful risk factor for unborn babies; (iv) provision of the added value (in the spirit of the Green Deal call) in scientifically-based tools for experimental screening, digital pre-screening, and analysis of chemicals and pharmaceuticals on their potential to cross placental tissue barriers.
Altogether this will provide a rationale for risk classification of existing and new compounds, as well as justifications of regulations and risk assessment/mitigation measures towards the potential effects of these compounds on pregnant women and fetal health.
The LIFESAVER project has the potential to contribute to several key EU strategies and offers a solution to several challenges highlighted by the European Commission. The project is in alignment with the objectives set in the European Green Deal (COM/2019/640 final), the recent EU Action Plan: 'Towards Zero Pollution for Air, Water and Soil’ (COM/2021/400 final) and the EU Chemicals Strategy for Sustainability (COM/2020/667 final). Indeed, by developing a new solution to determine and assess the impact of pollutants, chemicals and medicines on pregnant women and foetuses, the project is able to identify harmful components, and can hence contribute to the ability to better protect citizens and move towards a toxic-free environment. Finally, the project contributes to the Pharmaceutical Strategy for Europe (COM/2020/761 final), which, amongst others, underscores the lack of treatments for specific population groups such as pregnant women and urges for technological advances to address such issues.
During the first stage of the LIFESAVER project the partners have defined the key conditions to replicate placental environment in the laboratory setup, formulated and successfully produced first batches of the cells including "immortalized" ones and applied them to bioinks for use in the 3D bioprinting process, assembled the first demonstrator of a microfludic system which mimics maternal and fetal blood flows circulation, digitally design and calculate parameters for two key elements (placental and amnion) which were also manufactured to be tested in the lab in the next steps. The first demonstrator has been assembled in June 2023 at INL (Laboratorio Iberico Internacional de Nanotecnologia), Braga, Portugal, by the partners ELVESYS and INL and has then been moved to i3S (Instituto de Investicagao e Inovacao en Saude da Universidade do Porto) where all the tests will be performed.
This has allowed analysis of selecting and processing core tissues and cells for use in bioprinting and for testing for cytotoxic behaviour when subjected to different chemicals, creating correlating numerical models for both placenta and for its in vitro model device, building up a microfluidic system for species transport in the LIFESAVER demonstrator device. In addition, the project has started dissemination and communication of the research outcomes and identification of exploitable results and pathways. A specific task has started in elaborating EU policy recommendations for further securing of the health of mother and fetus from environmental stresses and pharmachemicals.
The LIFESAVER project has a very good progress towards a "bio-digital twin" (combination of an in vitro placenta model system and its digital clone) to test how far and fast substances (drugs, chemicals) are transferred between mother and fetus, especially at the end of the first trimester of pregnancy. The challenges of this research are especially in properly replicating the conditions of pregnant uterine tissue, as there is very little information about them.
This has allowed analysis of selecting and processing core tissues and cells for use in bioprinting and for testing for cytotoxic behaviour when subjected to different chemicals, creating correlating numerical models for both placenta and for its in vitro model device, building up a microfluidic system for species transport in the LIFESAVER demonstrator device. In addition, the project has started dissemination and communication of the research outcomes and identification of exploitable results and pathways. A specific task has started in elaborating EU policy recommendations for further securing of the health of mother and fetus from environmental stresses and pharmachemicals.
The LIFESAVER project has a very good progress towards a "bio-digital twin" (combination of an in vitro placenta model system and its digital clone) to test how far and fast substances (drugs, chemicals) are transferred between mother and fetus, especially at the end of the first trimester of pregnancy. The challenges of this research are especially in properly replicating the conditions of pregnant uterine tissue, as there is very little information about them.
The new biodigital platform involves bioprinting a placental structure and an amniotic element using specialized cells that are properly stimulated to test the safety of chemicals and pharmaceuticals for pregnant women and to study the transmission of various substances from mother to fetus without putting real humans or animals at risk. The project's ultimate goal is to eliminate the need for animal testing and reduce the time and costs associated with clinical trials involving pregnant women.
By leveraging advanced technologies such as digitalization and 3D bioprinting, the LIFESAVER project could enhance the competitiveness and appeal of Europe's biomedical, pharmaceutical, and industrial sectors. Overall, the LIFESAVER platform has the potential to advance our knowledge of prenatal development and enhance safety for pregnant women.
By leveraging advanced technologies such as digitalization and 3D bioprinting, the LIFESAVER project could enhance the competitiveness and appeal of Europe's biomedical, pharmaceutical, and industrial sectors. Overall, the LIFESAVER platform has the potential to advance our knowledge of prenatal development and enhance safety for pregnant women.