Periodic Reporting for period 1 - ActiTOX (Active organotypic models for nanoparticle toxicological screening)
Période du rapport: 2019-08-01 au 2022-07-31
The ActiTOX project delivers a novel approach to the safety testing of nanomaterials.
Currently, nanoparticles and new drugs are tested in a complex safety assessment before they are used in products. However, the standard preclinical testing methods used here have considerable disadvantages, both from an ethical (animal testing) and functional (high failure rate in clinical tests) point of view.
ActiTOX is responding to this problem by developing a novel cell-based test platform. This is based on human induced pluripotent stem cells (hiPSCs), a powerful cell system that can differentiate into all tissue types and has been shown to recapitulate many properties of human cells and their response to drugs. hiPSCs are ethically safe and can be easily produced in large quantities from human donor cells, such as skin or blood cells.
By combining different cell models, which are applied to special biological carrier materials, and a fluidic system in which different cell types can be cultivated in individual compartments but linked to each other, ActiTOX creates a test platform for evaluating the uptake of nanoparticles/active substances in the body, their distribution in the organism and their metabolism and excretion.
ActiTOX aims to increase the relevance of in vitro studies by developing animal-free, more robust, physiology-based models and to provide a scalable approach for their use in drug development and toxicology screening.
In order to achieve the project goals, a training network enabling efficient short-term secondments of experienced and early-stage researchers between academia and industry will be established. The cooperation between stakeholders helps closing the gap between them and mediate innovation to foster the current state of the art. ActiTOX will mediate it via networking, research, training, workshop, innovation and dissemination actions. The project increases knowledge based economy and creates long lasting cooperation strengthening the European research area.
Currently, nanoparticles and new drugs are tested in a complex safety assessment before they are used in products. However, the standard preclinical testing methods used here have considerable disadvantages, both from an ethical (animal testing) and functional (high failure rate in clinical tests) point of view.
ActiTOX is responding to this problem by developing a novel cell-based test platform. This is based on human induced pluripotent stem cells (hiPSCs), a powerful cell system that can differentiate into all tissue types and has been shown to recapitulate many properties of human cells and their response to drugs. hiPSCs are ethically safe and can be easily produced in large quantities from human donor cells, such as skin or blood cells.
By combining different cell models, which are applied to special biological carrier materials, and a fluidic system in which different cell types can be cultivated in individual compartments but linked to each other, ActiTOX creates a test platform for evaluating the uptake of nanoparticles/active substances in the body, their distribution in the organism and their metabolism and excretion.
ActiTOX aims to increase the relevance of in vitro studies by developing animal-free, more robust, physiology-based models and to provide a scalable approach for their use in drug development and toxicology screening.
In order to achieve the project goals, a training network enabling efficient short-term secondments of experienced and early-stage researchers between academia and industry will be established. The cooperation between stakeholders helps closing the gap between them and mediate innovation to foster the current state of the art. ActiTOX will mediate it via networking, research, training, workshop, innovation and dissemination actions. The project increases knowledge based economy and creates long lasting cooperation strengthening the European research area.
In the project ActiTOX novel carrier materials from biocompatible polymers mimicking the structure of the environment of the cells in the human body. Therefore a needleless electrospinning technology were developed. Based on different polymers, differnt kinds of carrier material was fabricated and characterised. Successful functionalisation as well as incorporation of specific substances was achieved.
In parallel a novel fluidic platform with specific chambers for cell cultivation were developed and characterised to support the use of the carrier material in combination with differnt kinds of cellular models.
Organotypic models of lung, skin, intestine and hepatic tissue were established and their unctionality was tested on the differnt carrier materials
After assessing the biocompatibility of the carrier materials and the efficiency of cell viability and cell growth, the organotypic models were combined in the novel fluidic platform for a dynamic cell cultivation.
Besides the further development of the microfluidic platform for culturing different tissues in parallel and thus for the development of animal-free in vitro modles, one mail focus was also on the differentiation of human induced pluripotent stem cells (hiPSCs). A protocol for the differentiation of human iPSC-derived lung cells was developed and validated.
Most of the results are already published in peer-reviewed articles, some of the data is under revision for publication in peer-reviewed articles.
In parallel a novel fluidic platform with specific chambers for cell cultivation were developed and characterised to support the use of the carrier material in combination with differnt kinds of cellular models.
Organotypic models of lung, skin, intestine and hepatic tissue were established and their unctionality was tested on the differnt carrier materials
After assessing the biocompatibility of the carrier materials and the efficiency of cell viability and cell growth, the organotypic models were combined in the novel fluidic platform for a dynamic cell cultivation.
Besides the further development of the microfluidic platform for culturing different tissues in parallel and thus for the development of animal-free in vitro modles, one mail focus was also on the differentiation of human induced pluripotent stem cells (hiPSCs). A protocol for the differentiation of human iPSC-derived lung cells was developed and validated.
Most of the results are already published in peer-reviewed articles, some of the data is under revision for publication in peer-reviewed articles.
ActiTOX project achieved the following innovations until the end of the project:
- Optimization of electrospinning technology for the production of carrier materials for protein delivery
- Fabriation of coated and non-coated carrier material
- Successful release studies with drugs incorporated in the carrier material
- Design and fabrication of novel chambers for cultivation of different cell models in parallel
- Design and development of a microfluidic system for cultivation of cells under fluidic contitions and for implementation of studies regarding uptake of nanoparticles/active substances in the body, their distribution in the organism and their metabolism and excretion
- Successful development of protocols for the differentiation and cultivation of hiPSC- based cell models
- Development and validation of animal-free, robust, physiology-based models for their use in drug development and toxicology screening
- Knowledge transfer between academia and industry
- Initiate cooperations between stakeholders to help closing the gap between them and mediate innovation to foster the current state of the art
- Create long lasting cooperation strengthening the European research area
- Reduce animal testing
- Approaches for novel persanolised medicine
- Optimization of electrospinning technology for the production of carrier materials for protein delivery
- Fabriation of coated and non-coated carrier material
- Successful release studies with drugs incorporated in the carrier material
- Design and fabrication of novel chambers for cultivation of different cell models in parallel
- Design and development of a microfluidic system for cultivation of cells under fluidic contitions and for implementation of studies regarding uptake of nanoparticles/active substances in the body, their distribution in the organism and their metabolism and excretion
- Successful development of protocols for the differentiation and cultivation of hiPSC- based cell models
- Development and validation of animal-free, robust, physiology-based models for their use in drug development and toxicology screening
- Knowledge transfer between academia and industry
- Initiate cooperations between stakeholders to help closing the gap between them and mediate innovation to foster the current state of the art
- Create long lasting cooperation strengthening the European research area
- Reduce animal testing
- Approaches for novel persanolised medicine