Periodic Reporting for period 1 - BioMembrOS (Biomimetic Membranes for Organ Support)
Reporting period: 2024-01-01 to 2024-12-31
Respiratory diseases are the third largest cause of death in EU, acute respiratory distress syndrome (ARDS) is a severe condition associated with a mortality rate of above 30%. Currently available treatment options include mechanical ventilation and extracorporeal membrane oxygenation (ECMO), both associated with high morbidity and mortality. In ECMO, the gas exchange (O2 from sweep gas to blood, CO2 from blood to sweep gas) takes place through large bundles of hollow fiber membranes. As the hollow fibers do not replicate the lung sufficiently, the process has very low efficiency. Therefore, large oxygenators with high numbers of fibers are needed, big blood volumes have to be led outside the body where they come in contact with big artificial surfaces, leading to low hemocompatibility and occurrence of thrombosis and hemolysis.
Research with state-of-the-art methods has so far only led to incremental improvements, indicating that a radically new approach is needed. Among vertebrates, not humans but fish (which breath water) and birds (which respire air) have evolved the most efficient gas exchange (respiratory) organs, which differ from mammalian respiratory system, both in structure at micro- and macro-level, and exchange gas more efficiently.
The overall goal of BioMembrOS is to follow a ground breaking new biomimetic approach and replicate the main characteristics of the most efficient states and processes that have evolved in vertebrates in nature, mainly that of birds and fish, in order to develop a highly efficient bio/hemocompatible membrane structure for intracorporeal artificial respiration and as a platform technology also beyond.
Our aim is to develop membrane structures with radically new geometries and materials, with at least 50% surplus in both O2 and CO2 mass transfer per device unit volume in comparison to the currently available technology. Higher efficiency will mean much smaller, eventually implantable devices, smaller blood volumes needed in the oxygenator and higher hemocompatibility, which will contribute to better treatment with better outcomes and lower incidence of complications for high numbers of patients suffering from severe respiratory diseases.
To reach this goal, four specific objectives were defined:
1) Develop highly efficient bio-/hemocompatible membrane fibers with inner and outer structuring.
2) Develop optimized 3D membrane structures with geometric layout optimized for structural stability, mass transfer (boundary layer control), and hemocompatibility.
3) Develop 3D printed coated membrane structures with increased hemocompatibility and gas permeability from novel polyurethane based material.
4) Validation - benchmark: We will provide validation of the technology developed with our novel biomimetic approach.
Research with state-of-the-art methods has so far only led to incremental improvements, indicating that a radically new approach is needed. Among vertebrates, not humans but fish (which breath water) and birds (which respire air) have evolved the most efficient gas exchange (respiratory) organs, which differ from mammalian respiratory system, both in structure at micro- and macro-level, and exchange gas more efficiently.
The overall goal of BioMembrOS is to follow a ground breaking new biomimetic approach and replicate the main characteristics of the most efficient states and processes that have evolved in vertebrates in nature, mainly that of birds and fish, in order to develop a highly efficient bio/hemocompatible membrane structure for intracorporeal artificial respiration and as a platform technology also beyond.
Our aim is to develop membrane structures with radically new geometries and materials, with at least 50% surplus in both O2 and CO2 mass transfer per device unit volume in comparison to the currently available technology. Higher efficiency will mean much smaller, eventually implantable devices, smaller blood volumes needed in the oxygenator and higher hemocompatibility, which will contribute to better treatment with better outcomes and lower incidence of complications for high numbers of patients suffering from severe respiratory diseases.
To reach this goal, four specific objectives were defined:
1) Develop highly efficient bio-/hemocompatible membrane fibers with inner and outer structuring.
2) Develop optimized 3D membrane structures with geometric layout optimized for structural stability, mass transfer (boundary layer control), and hemocompatibility.
3) Develop 3D printed coated membrane structures with increased hemocompatibility and gas permeability from novel polyurethane based material.
4) Validation - benchmark: We will provide validation of the technology developed with our novel biomimetic approach.
The first milestone of the BioMembrOS project was the Specification Sheet, which was due at month 9 in the first project year. To reach this milestone, we investigated functional features of bird lungs and fish gills that are suitable for replication in our biomimetic approach and derived the required technical features.
In the first year of the project, in order to reach Objective 1, we have 1) developed a suitable CFD platform with geometries implementation and meshing workflows plus suitable solver settings to account for gas and liquid flow including thermodynamic and kinetic properties of blood; 2) performed extensive CFD studies on flow and mass transfer of oxygen and carbon dioxide from/to the fiber lumen side to the shell side where the specific properties of blood flow was accounted for. 3) and further, preferential fiber arrangements were analysed.
Experimentally, a 3D printing workflow with transparent dyes was successfully implemented to 3D print complex structured fiber arrangement in lab-on-a-chip designs for µ-PIV flow investigations. This allowed the flow investigation of differently structured fibers for the successful validation of CFD simulations
In order to reach Objective 2, in the first project year, 3D printing of transparent „lab-on-a-chip“ systems were investigated. A review paper was prepared and published on 3D printing of small structures – summarizing latest developments in the field (DOI: https://doi.org/10.3390/polym17040455(opens in new window)). Further, two 3D printing systems were selected to meet resolution requirements and capabilities and installed at UNIBO and TUW for following purposes:
• One 3D printer to print fully transparent devices for laser-based flow analysis
• One 3D printer for immersion precipitation 3D printing of membranes
In order to reach Objective 3, stable MOF nanodispersions and bi-soft segment PUR/PCL membranes were prepared. The polymer/solvent ratio was optimized to achieve membrane-forming casting solutions. The optimized protocol was applied to prepare flat sheet dense symmetric and bi-soft segment PUR/PCL membranes and flat sheet integrally asymmetric bi-soft segment PUR/PCL membranes. As a promising alternative for bi-soft segment PU, thermoplastic polyurethanes (TPUs) membranes were analysed. The production of suitable TPU casting solutions was optimized and applied to produce flat sheet dense symmetric TPU-based membranes. Permeation rates of flat sheet dense symmetric TPU-based membranes were assessed and flat sheet integrally asymmetric TPU-based membranes were successfully produced for the first time. The production of MOF nanodispersions to obtain both dense symmetric and integrally asymmetric Mixed Matrix Membranes (MMMs) was initiated and first promising preliminary results were achieved.
In preparation of activities in the second project project year towards Objective 4, validation test systems were prepared for gas transfer and permeance measurements of flat-sheet and capillary membranes. Further, preparations for in-vitro tests were initiated. Both systems are ready for tests starting in the second project period.
In the first year of the project, in order to reach Objective 1, we have 1) developed a suitable CFD platform with geometries implementation and meshing workflows plus suitable solver settings to account for gas and liquid flow including thermodynamic and kinetic properties of blood; 2) performed extensive CFD studies on flow and mass transfer of oxygen and carbon dioxide from/to the fiber lumen side to the shell side where the specific properties of blood flow was accounted for. 3) and further, preferential fiber arrangements were analysed.
Experimentally, a 3D printing workflow with transparent dyes was successfully implemented to 3D print complex structured fiber arrangement in lab-on-a-chip designs for µ-PIV flow investigations. This allowed the flow investigation of differently structured fibers for the successful validation of CFD simulations
In order to reach Objective 2, in the first project year, 3D printing of transparent „lab-on-a-chip“ systems were investigated. A review paper was prepared and published on 3D printing of small structures – summarizing latest developments in the field (DOI: https://doi.org/10.3390/polym17040455(opens in new window)). Further, two 3D printing systems were selected to meet resolution requirements and capabilities and installed at UNIBO and TUW for following purposes:
• One 3D printer to print fully transparent devices for laser-based flow analysis
• One 3D printer for immersion precipitation 3D printing of membranes
In order to reach Objective 3, stable MOF nanodispersions and bi-soft segment PUR/PCL membranes were prepared. The polymer/solvent ratio was optimized to achieve membrane-forming casting solutions. The optimized protocol was applied to prepare flat sheet dense symmetric and bi-soft segment PUR/PCL membranes and flat sheet integrally asymmetric bi-soft segment PUR/PCL membranes. As a promising alternative for bi-soft segment PU, thermoplastic polyurethanes (TPUs) membranes were analysed. The production of suitable TPU casting solutions was optimized and applied to produce flat sheet dense symmetric TPU-based membranes. Permeation rates of flat sheet dense symmetric TPU-based membranes were assessed and flat sheet integrally asymmetric TPU-based membranes were successfully produced for the first time. The production of MOF nanodispersions to obtain both dense symmetric and integrally asymmetric Mixed Matrix Membranes (MMMs) was initiated and first promising preliminary results were achieved.
In preparation of activities in the second project project year towards Objective 4, validation test systems were prepared for gas transfer and permeance measurements of flat-sheet and capillary membranes. Further, preparations for in-vitro tests were initiated. Both systems are ready for tests starting in the second project period.
In the first year of BioMembrOS we have submitted two journal papers, of which one, a review paper on 3D printing small structures (DOI: https://doi.org/10.3390/polym17040455(opens in new window))
has already been accepted and published. Members of the consortium contributed four oral presentations and three poster presentations at scientific conferences, two seminars and two workshops were held. In the BioMembrOS community on the Zenodo platform (https://zenodo.org/communities/biomembros/(opens in new window)) part of the EU Open Research Repository datasets, publications and presentations have already been made available.
For communication of the project and its goals we have designed a project folder (see attached figures), online information is available on the BioMembrOS webpage (https://biomembros.eu/(opens in new window)) and our social media presences, which are all also reachable via the website, inform on the projects activities and results continuously.
Also, we have identified five innovations within the first year of BioMembrOS, that will be further investigated on their potential impact both as stand-alone innovations and as part of the BioMembrOS platform technology.
has already been accepted and published. Members of the consortium contributed four oral presentations and three poster presentations at scientific conferences, two seminars and two workshops were held. In the BioMembrOS community on the Zenodo platform (https://zenodo.org/communities/biomembros/(opens in new window)) part of the EU Open Research Repository datasets, publications and presentations have already been made available.
For communication of the project and its goals we have designed a project folder (see attached figures), online information is available on the BioMembrOS webpage (https://biomembros.eu/(opens in new window)) and our social media presences, which are all also reachable via the website, inform on the projects activities and results continuously.
Also, we have identified five innovations within the first year of BioMembrOS, that will be further investigated on their potential impact both as stand-alone innovations and as part of the BioMembrOS platform technology.