Periodic Reporting for period 3 - LIFESAVER (Living Impact on Fetal Evolution: Shelter-Analyze-Validate-Empower Regulations)
Periodo di rendicontazione: 2024-11-01 al 2025-10-31
The safety of medicines and environmental chemical exposures during pregnancy remains a major challenge in healthcare and regulatory science. Pregnant women are rarely included in clinical trials, and current risk assessment approaches rely heavily on animal testing or limited human data. As a result, there is significant uncertainty in understanding how pharmaceuticals and environmental pollutants affect the developing fetus, contributing to serious public health concerns such as preterm birth, neonatal mortality, and long-term health complications.
LIFESAVER addressed this challenge by developing a new scientific and technological framework to improve the assessment of risks to maternal and fetal health. The project aimed to generate robust, human-relevant data and tools to support more reliable and evidence-based regulatory decision-making, in line with European priorities on zero pollution, reduced animal testing, and safer medicines.
To achieve this, LIFESAVER developed an integrated biodigital approach combining advanced in vitro and in silico methods. This included bioengineered models of the placental interface, innovative bioprinting technologies, biosensing systems, and computational models to predict substance transfer and toxicity. These components were brought together into a functional biodigital twin prototype supported by validated cell models, scalable membrane technologies, and a microphysiological system platform.
The project also generated new experimental datasets, validated testing methodologies, and contributed to the development of New Approach Methodologies for maternal–fetal risk assessment. In parallel, LIFESAVER developed a policy toolbox and engaged with regulatory and industry stakeholders to support the integration of these approaches into future regulatory frameworks.
Conclusions of the action:
LIFESAVER successfully demonstrated the feasibility of a biodigital platform for assessing drug and chemical safety during pregnancy. The project delivered validated tools, datasets, and a functional prototype that together provide a stronger scientific basis for evaluating maternal–fetal exposure.
The results show that combining in vitro and in silico approaches can significantly improve the prediction of fetal exposure and risk, enabling safer use of medicines and better protection of unborn children. This approach supports the transition away from animal testing and contributes to the development of regulatory endpoints for future risk assessment frameworks.
LIFESAVER also established a clear pathway for further development and uptake, including engagement with pharmaceutical stakeholders as early adopters and the definition of a post-project exploitation strategy.
Overall, the project has delivered a significant step forward in enabling more reliable, ethical, and data-driven approaches to maternal and fetal health assessment. It contributes to European policy objectives under the Green Deal, the Zero Pollution Action Plan, the Chemicals Strategy for Sustainability, and the Pharmaceutical Strategy for Europe, while supporting innovation and safer healthcare for pregnant women and their children.
LIFESAVER addressed this challenge by developing a new scientific and technological framework to improve the assessment of risks to maternal and fetal health. The project aimed to generate robust, human-relevant data and tools to support more reliable and evidence-based regulatory decision-making, in line with European priorities on zero pollution, reduced animal testing, and safer medicines.
To achieve this, LIFESAVER developed an integrated biodigital approach combining advanced in vitro and in silico methods. This included bioengineered models of the placental interface, innovative bioprinting technologies, biosensing systems, and computational models to predict substance transfer and toxicity. These components were brought together into a functional biodigital twin prototype supported by validated cell models, scalable membrane technologies, and a microphysiological system platform.
The project also generated new experimental datasets, validated testing methodologies, and contributed to the development of New Approach Methodologies for maternal–fetal risk assessment. In parallel, LIFESAVER developed a policy toolbox and engaged with regulatory and industry stakeholders to support the integration of these approaches into future regulatory frameworks.
Conclusions of the action:
LIFESAVER successfully demonstrated the feasibility of a biodigital platform for assessing drug and chemical safety during pregnancy. The project delivered validated tools, datasets, and a functional prototype that together provide a stronger scientific basis for evaluating maternal–fetal exposure.
The results show that combining in vitro and in silico approaches can significantly improve the prediction of fetal exposure and risk, enabling safer use of medicines and better protection of unborn children. This approach supports the transition away from animal testing and contributes to the development of regulatory endpoints for future risk assessment frameworks.
LIFESAVER also established a clear pathway for further development and uptake, including engagement with pharmaceutical stakeholders as early adopters and the definition of a post-project exploitation strategy.
Overall, the project has delivered a significant step forward in enabling more reliable, ethical, and data-driven approaches to maternal and fetal health assessment. It contributes to European policy objectives under the Green Deal, the Zero Pollution Action Plan, the Chemicals Strategy for Sustainability, and the Pharmaceutical Strategy for Europe, while supporting innovation and safer healthcare for pregnant women and their children.
Over its full duration LIFESAVER successfully designed, produced, and validated the first biodigital twin platform that integrates in vitro and in silico models to replicate placental barrier function and predict maternal–fetal chemical transfer with unprecedented fidelity.
Final Period Achievements
1. Biodigital Twin Completion: The “biodigital twin” concept was for the first time designed and realised as a connected combination of micro-physiological systems (MPS) with tandem digital simulations of maternal and fetal blood flows.
Here experimental data from in vitro system were linked with 3D in silico placenta models, achieving validated higher biofidelity and allowing simultaneous prediction and measurement of substance transport kinetics .
2. Cellular Innovation and DIANA construct: Fully established immortalized human placental and amniotic cell lines, enabling reproducible, ethically sustainable testing combined with the novel DIANA (“drop-in-a-net assembly”) concept for producing ultra-thin, yet stable and scalable core membranes — the foundation of the LIFESAVER model.
3. Microfluidic Platform: Implemented advanced features such as automated micro-volume multiply sampling, dissolved gas regulation, and liquid recirculation control (patent pending) to ensure precise and repeatable experiments.
Demonstrated operational prototypes ready for regulatory and industrial validation.
4. Predictive Modeling and Data Integration: Created comprehensive algorithms for data processing and simulation, linking in vitro experiments to digital twins, connected to multiple Design of Experiments (DoE) campaigns for calibration, validating chemical transport models and biomarker responses.
5. Analytical Advances: Integrated real-time and high-throughput biosensors for early biomarkers of toxicity and cells reactivity. Published in peer-reviewed journals including ACS Sensors, Cell Death and Discovery, Frontiers in Cell and Developmental Biology, Biosensors and Advanced Materials Technologies.
6. Policy and Dissemination Achievements: Developed a Policy Toolbox translating recommendations into practical actions for regulators, researchers, and industry. Policy briefs advocate integration of pregnancy-specific safety data, validation of New Approach Methodologies (NAMs) and adaptation of EU regulatory frameworks to enable animal-free testing. Dissemination through EU-level events, conferences, and a final event “Securing Better Lives: a LIFESAVER Story” (Brussels, Oct 2025).
Main Results:
Fully functional LIFESAVER biodigital twin prototype combining biological, computational, and regulatory dimensions.
Validated immortalized cell models and scalable DIANA membranes as exploitable biotechnological assets.
MPS platform and sensor systems under IP protection and ready for technology transfer.
Policy toolbox and recommendations adopted by stakeholders to guide NAMs in maternal–fetal health assessments.
Final Period Achievements
1. Biodigital Twin Completion: The “biodigital twin” concept was for the first time designed and realised as a connected combination of micro-physiological systems (MPS) with tandem digital simulations of maternal and fetal blood flows.
Here experimental data from in vitro system were linked with 3D in silico placenta models, achieving validated higher biofidelity and allowing simultaneous prediction and measurement of substance transport kinetics .
2. Cellular Innovation and DIANA construct: Fully established immortalized human placental and amniotic cell lines, enabling reproducible, ethically sustainable testing combined with the novel DIANA (“drop-in-a-net assembly”) concept for producing ultra-thin, yet stable and scalable core membranes — the foundation of the LIFESAVER model.
3. Microfluidic Platform: Implemented advanced features such as automated micro-volume multiply sampling, dissolved gas regulation, and liquid recirculation control (patent pending) to ensure precise and repeatable experiments.
Demonstrated operational prototypes ready for regulatory and industrial validation.
4. Predictive Modeling and Data Integration: Created comprehensive algorithms for data processing and simulation, linking in vitro experiments to digital twins, connected to multiple Design of Experiments (DoE) campaigns for calibration, validating chemical transport models and biomarker responses.
5. Analytical Advances: Integrated real-time and high-throughput biosensors for early biomarkers of toxicity and cells reactivity. Published in peer-reviewed journals including ACS Sensors, Cell Death and Discovery, Frontiers in Cell and Developmental Biology, Biosensors and Advanced Materials Technologies.
6. Policy and Dissemination Achievements: Developed a Policy Toolbox translating recommendations into practical actions for regulators, researchers, and industry. Policy briefs advocate integration of pregnancy-specific safety data, validation of New Approach Methodologies (NAMs) and adaptation of EU regulatory frameworks to enable animal-free testing. Dissemination through EU-level events, conferences, and a final event “Securing Better Lives: a LIFESAVER Story” (Brussels, Oct 2025).
Main Results:
Fully functional LIFESAVER biodigital twin prototype combining biological, computational, and regulatory dimensions.
Validated immortalized cell models and scalable DIANA membranes as exploitable biotechnological assets.
MPS platform and sensor systems under IP protection and ready for technology transfer.
Policy toolbox and recommendations adopted by stakeholders to guide NAMs in maternal–fetal health assessments.
LIFESAVER has delivered a world-first biodigital twin that merges in vitro biological modeling with in silico simulation for the placental interface. It goes far beyond existing organ-on-chip systems by combining real cellular physiology with dynamic computational prediction, achieving human-level biofidelity unattainable in animal or synthetic systems. The DIANA fabrication method, immortalized cell lines, and advanced microfluidic and sensor integration set new standards for reproducibility, scalability, and regulatory validation. Together these innovations offer a robust, ethical, and cost-effective alternative to animal and clinical testing in pregnancy-related pharmacology.
Expected Results and Exploitation
- A validated biodigital twin platform compliant with regulatory needs for chemicals and drug testing.
- Standardized operational protocols for NAM validation, facilitating regulatory submissions.
- Active exploitation of the DIANA membrane and MPS modules for pharma and toxicology markets.
- Ongoing stakeholder engagement ensuring technology adoption by regulators, pharma industry, and research institutions.
Potential Impacts
1. Socio-Economic and Industrial Impacts
- Significant reduction in animal use and testing costs across pharmaceutical and chemical sectors.
- Acceleration of safe medicine development for pregnant women, enabling faster time-to-market and compliance with EU Green Deal goals.
- Strengthened European leadership in NAMs, MPS and predictive biosciences with potential cross-sector applications.
2. Wider Societal Implications
- Improved maternal and fetal safety through reliable, non-invasive risk assessment tools.
- Contribution to global standards on prenatal testing ethics and human health protection.
- Empowerment of policymakers and healthcare professionals with scientifically grounded evidence.
- The potential to safeguard the health of over 180 million pregnant women annually worldwide, ensuring healthier generations to come .
Conclusion: LIFESAVER successfully bridged scientific innovation, ethics, and policy — delivering a validated biodigital twin as a transformative tool for maternal–fetal health protection and a cornerstone in Europe’s transition toward humane, data-driven, and sustainable biomedical research.
Expected Results and Exploitation
- A validated biodigital twin platform compliant with regulatory needs for chemicals and drug testing.
- Standardized operational protocols for NAM validation, facilitating regulatory submissions.
- Active exploitation of the DIANA membrane and MPS modules for pharma and toxicology markets.
- Ongoing stakeholder engagement ensuring technology adoption by regulators, pharma industry, and research institutions.
Potential Impacts
1. Socio-Economic and Industrial Impacts
- Significant reduction in animal use and testing costs across pharmaceutical and chemical sectors.
- Acceleration of safe medicine development for pregnant women, enabling faster time-to-market and compliance with EU Green Deal goals.
- Strengthened European leadership in NAMs, MPS and predictive biosciences with potential cross-sector applications.
2. Wider Societal Implications
- Improved maternal and fetal safety through reliable, non-invasive risk assessment tools.
- Contribution to global standards on prenatal testing ethics and human health protection.
- Empowerment of policymakers and healthcare professionals with scientifically grounded evidence.
- The potential to safeguard the health of over 180 million pregnant women annually worldwide, ensuring healthier generations to come .
Conclusion: LIFESAVER successfully bridged scientific innovation, ethics, and policy — delivering a validated biodigital twin as a transformative tool for maternal–fetal health protection and a cornerstone in Europe’s transition toward humane, data-driven, and sustainable biomedical research.