Periodic Reporting for period 2 - LIFESAVER (Living Impact on Fetal Evolution: Shelter-Analyze-Validate-Empower Regulations)
Berichtszeitraum: 2023-05-01 bis 2024-10-31
In Europe, 75% of neonatal deaths and 60% of infant deaths occur in preterm infants, with 450 neonatal deaths happening every hour globally. Preterm births are rising due to later pregnancies, environmental threats, increased medication use, and inadequate treatments. The LIFESAVER project addresses these pressing societal and healthcare needs by building a scientific foundation for regulatory approaches to maternal and fetal health. It focuses on generating and validating data to forecast the effects of environmental pollutants and pharmaceutical treatments on pregnant women, challenges that are otherwise difficult to assess.
Premature births not only increase neonatal deaths but also lead to long-term health issues, including infections, diabetes, cerebral palsy, and cognitive impairment, imposing significant societal and economic burdens. LIFESAVER offers experimental and digital solutions to improve prenatal healthcare using its biodigital twin in vitro devices, advancing innovation in bioprinting, tissue engineering, and pharmacology, while enhancing Europe’s competitiveness in these fields.
The project aims to develop a digitally cloned in vitro system that emulates prenatal conditions near the placental interface with high biofidelity—replicating organ functionality, not just structure. This system provides risk predictions for harmful substances, supporting improved regulations for protecting fetuses. Its goals include:
Safeguarding pregnant women and fetuses with scientifically justified chemical and medicinal regulations.
Demonstrating a biofidelic system for studying prenatal conditions.
Creating tools for experimental and digital chemical screening to assess placental barrier permeability.
Enabling risk classification and justification for regulatory measures to mitigate harmful impacts on maternal and fetal health.
The LIFESAVER project aligns with key EU strategies, including the European Green Deal, the EU Action Plan for Zero Pollution, and the EU Chemicals Strategy for Sustainability, by identifying harmful pollutants, chemicals, and medicines to protect citizens and promote a toxic-free environment. It also supports the Pharmaceutical Strategy for Europe, addressing gaps in treatments for pregnant women and fostering technological advances in prenatal health.
Premature births not only increase neonatal deaths but also lead to long-term health issues, including infections, diabetes, cerebral palsy, and cognitive impairment, imposing significant societal and economic burdens. LIFESAVER offers experimental and digital solutions to improve prenatal healthcare using its biodigital twin in vitro devices, advancing innovation in bioprinting, tissue engineering, and pharmacology, while enhancing Europe’s competitiveness in these fields.
The project aims to develop a digitally cloned in vitro system that emulates prenatal conditions near the placental interface with high biofidelity—replicating organ functionality, not just structure. This system provides risk predictions for harmful substances, supporting improved regulations for protecting fetuses. Its goals include:
Safeguarding pregnant women and fetuses with scientifically justified chemical and medicinal regulations.
Demonstrating a biofidelic system for studying prenatal conditions.
Creating tools for experimental and digital chemical screening to assess placental barrier permeability.
Enabling risk classification and justification for regulatory measures to mitigate harmful impacts on maternal and fetal health.
The LIFESAVER project aligns with key EU strategies, including the European Green Deal, the EU Action Plan for Zero Pollution, and the EU Chemicals Strategy for Sustainability, by identifying harmful pollutants, chemicals, and medicines to protect citizens and promote a toxic-free environment. It also supports the Pharmaceutical Strategy for Europe, addressing gaps in treatments for pregnant women and fostering technological advances in prenatal health.
Since its inception, the LIFESAVER project has aimed to develop a bio-digital twin system emulating the placental environment to assess chemical and pharmaceutical transfer between mother and fetus.
Initial Stages (M1–M18)
1. Foundation Established:
- Defined boundary conditions for in vitro and in silico placental models to be translated into the optimized system design.
2. Cells Preparation:
- Produced initial batches of placental and amniotic cells, including immortalized lines, for 3D bioprinting, which are intended to replicate placental tissues functionality.
3. Prototype Development:
- Built and tested the first microfluidic system mimicking maternal-fetal blood flow.
4. Dissemination:
- Shared initial results and developed preliminary EU policy recommendations.
Progress During M19–M36
1. Cell Culture Advancements:
- Optimized culture and preservation of human placental and amniotic cells; successful immortalization of some cell lines to result in a sustainable availability of cell culture lines.
2. Bioprinting Breakthroughs:
- Developed advanced bioinks and successfully bioprinted membrane constructs using novel concept allowing scalability and repeatability.
3. Microfluidic Refinement:
- Enhanced chip designs with better sealing, oxygen and CO2 sensing, and flow/pressure regulation, with the first mock-up of the GUI for the system operation.
4. Bio-Digital Twin Development:
- Integrated first experimental and virtual data into predictive computational models leading to 2 tandem models (for a microfluidic chip and for a realistic 3D placentome).
5. Testing and Validation:
- Conducted cytotoxicity tests, validated barrier integrity in bioprinted constructs, tested mixtures of the drug and pollutants on cells viability.
6. Exploitation and Dissemination:
- Identified key exploitable results like the microfluidic platform and biosensors, first engagement with user and regulators stakeholders.
7. Policy Contributions:
- First draft of policy briefs and recommendations on mitigating maternal and fetal health risks.
Main Results Achieved So Far
1. Core Technologies:
- Developed and tested the bio-digital twin integrating in vitro models and simulations.
2. Progress Toward Objectives:
- Validated chemical transport models and standardized protocols.
3. Commercialization Efforts:
- Promoted exploitable results through stakeholder engagement.
4. Future Impact:
- Potential to reduce or eliminate animal testing and improve prenatal risk assessments.
Initial Stages (M1–M18)
1. Foundation Established:
- Defined boundary conditions for in vitro and in silico placental models to be translated into the optimized system design.
2. Cells Preparation:
- Produced initial batches of placental and amniotic cells, including immortalized lines, for 3D bioprinting, which are intended to replicate placental tissues functionality.
3. Prototype Development:
- Built and tested the first microfluidic system mimicking maternal-fetal blood flow.
4. Dissemination:
- Shared initial results and developed preliminary EU policy recommendations.
Progress During M19–M36
1. Cell Culture Advancements:
- Optimized culture and preservation of human placental and amniotic cells; successful immortalization of some cell lines to result in a sustainable availability of cell culture lines.
2. Bioprinting Breakthroughs:
- Developed advanced bioinks and successfully bioprinted membrane constructs using novel concept allowing scalability and repeatability.
3. Microfluidic Refinement:
- Enhanced chip designs with better sealing, oxygen and CO2 sensing, and flow/pressure regulation, with the first mock-up of the GUI for the system operation.
4. Bio-Digital Twin Development:
- Integrated first experimental and virtual data into predictive computational models leading to 2 tandem models (for a microfluidic chip and for a realistic 3D placentome).
5. Testing and Validation:
- Conducted cytotoxicity tests, validated barrier integrity in bioprinted constructs, tested mixtures of the drug and pollutants on cells viability.
6. Exploitation and Dissemination:
- Identified key exploitable results like the microfluidic platform and biosensors, first engagement with user and regulators stakeholders.
7. Policy Contributions:
- First draft of policy briefs and recommendations on mitigating maternal and fetal health risks.
Main Results Achieved So Far
1. Core Technologies:
- Developed and tested the bio-digital twin integrating in vitro models and simulations.
2. Progress Toward Objectives:
- Validated chemical transport models and standardized protocols.
3. Commercialization Efforts:
- Promoted exploitable results through stakeholder engagement.
4. Future Impact:
- Potential to reduce or eliminate animal testing and improve prenatal risk assessments.
The LIFESAVER project combines 3D bioprinting and computational modeling to create a hybrid bio-digital twin. Using advanced bioinks and human cells, it develops functional placental models, offering an ethical, accurate alternative to animal testing for assessing chemical and pharmaceutical safety during early pregnancy. This innovative in vitro and in silico approach addresses critical gaps in prenatal science, providing new insights into maternal-fetal interactions.
Expected Results Until the End of the Project
1 A Fully Functional Bio-Digital Twin:
Validated in vitro and in silico platform for high-output testing.
Reliable, regulatory-aligned chemical transport assessment methods.
2 Optimized Testing Frameworks:
Standardized protocols for experiments and regulatory submissions.
3 Validated Risk Assessment Models:
Tools to predict fetal exposure risks from toxins and pharmaceuticals.
4 Stakeholder and Policy Impact:
Policy recommendations and training for platform adoption.
Potential Impacts
Socio-Economic Impacts:
1 Ethical, cost-effective alternative to animal testing, reducing costs and accelerating development in pharmaceuticals and chemicals.
2 Enhancing Europe’s leadership in biomedical innovation, with safer product development across industries like cosmetics and environmental science.
Wider Societal Implications:
1 Improved tools to evaluate chemical exposure risks and safeguard maternal and fetal health.
2 Alignment with societal demands for humane research practices and reliable safety information for pregnant women.
3 Raising public awareness of prenatal risks and training interdisciplinary researchers.
Expected Results Until the End of the Project
1 A Fully Functional Bio-Digital Twin:
Validated in vitro and in silico platform for high-output testing.
Reliable, regulatory-aligned chemical transport assessment methods.
2 Optimized Testing Frameworks:
Standardized protocols for experiments and regulatory submissions.
3 Validated Risk Assessment Models:
Tools to predict fetal exposure risks from toxins and pharmaceuticals.
4 Stakeholder and Policy Impact:
Policy recommendations and training for platform adoption.
Potential Impacts
Socio-Economic Impacts:
1 Ethical, cost-effective alternative to animal testing, reducing costs and accelerating development in pharmaceuticals and chemicals.
2 Enhancing Europe’s leadership in biomedical innovation, with safer product development across industries like cosmetics and environmental science.
Wider Societal Implications:
1 Improved tools to evaluate chemical exposure risks and safeguard maternal and fetal health.
2 Alignment with societal demands for humane research practices and reliable safety information for pregnant women.
3 Raising public awareness of prenatal risks and training interdisciplinary researchers.