Periodic Reporting for period 1 - CellFreeImplant (Cell-free Ti-based Medical Implants due to Laser-induced Microstructures)
Période du rapport: 2018-07-01 au 2019-12-31
The project CellFreeImplant, “Cell-free Ti-based Medical Implants due to Laser-induced Microstructures”, has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 800832. This project was a Coordination and Support Action in the framework of the FET Innovation Launchpad scheme, which aims at turning results from FET-funded projects into genuine societal or economic innovations. It brought together 3 partners from 2 different countries. The project consortium is very interdisciplinary combining renowned experts from the fields of physics, mechatronics, life sciences, electrochemistry, laser-matter interaction, and practical medicine (especially cardiology).
New miniaturized and smart medical implants are more and more used in all medical fields, including miniaturized pacemakers. These implants with a casing consisting often of a Ti-alloy may have to be removed after some months or several years and shall therefore not be completely overgrown by the cells. In the framework of the recently finished FET Open project LiNaBioFluid, we successfully demonstrated that self-organized sharp cones or spikes covered with sub-micrometer ripples at Ti-alloy substrates created by pulsed laser-ablation can provide too little surface for the cells to grow on. Compared to flat surfaces, the cell density on the microstructures is significantly lowered, the coverage is incomplete and the cells have a clearly different morphology. The best results regarding suppression of cell growth are obtained on structures created by femtosecond Ti:sapphire laser irradiation, which are subsequently electrochemically treated.
The main goal of CellFreeImplant was to find partners for future development of implants addressing wide-spread patients' needs. We wanted to identify at least four different market segments in the field of miniaturized and smart medical implants. We provided customized samples with surfaces with femtosecond laser-induced micro- and nano-structures optionally combined with electrochemically oxidation for assessment of the technology by end-users, which were commercial producers of medical implants and prostheses.
Parallel to the assessment, business scenarios should be developed how the medical implants with our novel surface treatment could be produced in future and which steps have to be taken on this pathway to commercialization.
New miniaturized and smart medical implants are more and more used in all medical fields, including miniaturized pacemakers. These implants with a casing consisting often of a Ti-alloy may have to be removed after some months or several years and shall therefore not be completely overgrown by the cells. In the framework of the recently finished FET Open project LiNaBioFluid, we successfully demonstrated that self-organized sharp cones or spikes covered with sub-micrometer ripples at Ti-alloy substrates created by pulsed laser-ablation can provide too little surface for the cells to grow on. Compared to flat surfaces, the cell density on the microstructures is significantly lowered, the coverage is incomplete and the cells have a clearly different morphology. The best results regarding suppression of cell growth are obtained on structures created by femtosecond Ti:sapphire laser irradiation, which are subsequently electrochemically treated.
The main goal of CellFreeImplant was to find partners for future development of implants addressing wide-spread patients' needs. We wanted to identify at least four different market segments in the field of miniaturized and smart medical implants. We provided customized samples with surfaces with femtosecond laser-induced micro- and nano-structures optionally combined with electrochemically oxidation for assessment of the technology by end-users, which were commercial producers of medical implants and prostheses.
Parallel to the assessment, business scenarios should be developed how the medical implants with our novel surface treatment could be produced in future and which steps have to be taken on this pathway to commercialization.
"The project CellFreeImplant was divided into 3 work packages (WPs). WP1 took care of project management. WP2 concentrated on the structuring and electrochemical treatment of implant and prosthesis materials as well as on the biological assessment of the processed samples. The activities for dissemination and exploitation of project results were handled in WP3.
The materials processed in WP2 were Ti-based casings, plates, and screws for cardiovascular implants and post-trauma bone fixation, respectively, together with flat control samples of comparable composition. Also, polymer materials for future use in orthotic prostheses were investigated. The biological assessment was mainly based on in-vitro tests using cells from commercial cell lines, i.e. fibroblasts and osteoblasts, which form scar-tissue and bone-material, respectively.
Key innovation points of WP3 ""Dissemination and exploitation"" were:
• Networking with potential end-users of the CellFreeImplant results
• Activities to attract future cooperation partners and investors: participation at pitch event; exhibition stand at conference; contribution to ""Future Board""; creation of result on innovation platform
• Clarification of the patent situation
• Two published and three submitted articles in international, peer-reviewed scientific journals, one published abstract in a cardiology journal
• Nine oral presentations and posters by all partners at international scientific conferences and workshops, several invited
• The Laser Institute of America (LIA) has published a three-page feature article ""Surface Functionalization with LIPSS Continues to Expand into New Industries"" in their ""LIA TODAY"" newsletter, which mentions the project CellFreeImplant
• Social media accounts with scientific impact: ResearchGate account of CellFreeImplant with more than 700 “Reads” and 15 “Followers”"
The materials processed in WP2 were Ti-based casings, plates, and screws for cardiovascular implants and post-trauma bone fixation, respectively, together with flat control samples of comparable composition. Also, polymer materials for future use in orthotic prostheses were investigated. The biological assessment was mainly based on in-vitro tests using cells from commercial cell lines, i.e. fibroblasts and osteoblasts, which form scar-tissue and bone-material, respectively.
Key innovation points of WP3 ""Dissemination and exploitation"" were:
• Networking with potential end-users of the CellFreeImplant results
• Activities to attract future cooperation partners and investors: participation at pitch event; exhibition stand at conference; contribution to ""Future Board""; creation of result on innovation platform
• Clarification of the patent situation
• Two published and three submitted articles in international, peer-reviewed scientific journals, one published abstract in a cardiology journal
• Nine oral presentations and posters by all partners at international scientific conferences and workshops, several invited
• The Laser Institute of America (LIA) has published a three-page feature article ""Surface Functionalization with LIPSS Continues to Expand into New Industries"" in their ""LIA TODAY"" newsletter, which mentions the project CellFreeImplant
• Social media accounts with scientific impact: ResearchGate account of CellFreeImplant with more than 700 “Reads” and 15 “Followers”"
In total, four producers of medical implants and prostheses have been identified who assessed test samples with cell-repellent laser-induced microstructures of the CellFreeImplant project, including two global acting corporations and two innovative SMEs.
The three main results of the CellFreeImplant project were:
1. Ti-based casings of miniaturized cylindrical implants can be ultrafast-laser processed and anodized to form cell-repellent micro/nano-structures in a ring on their surface. Comparable rings on Ti-cylinders of same composition cannot be overgrown by cells in in-vitro tests in cell culture.
2. Areas which repel cells can be formed on pre-anodized bone plates from commercial production by ultrafast-laser processing.
3. Areas which repel cells can be formed on polymer samples for orthotic prostheses by ultrafast-laser processing.
The possibility of ingrowth of the implanted medical devices, which may complicate their removal after several months or years, for instance for replacement of the battery, restricts the use of these modern implant currently. If this problem could be convincingly solved, application to much more patients would be advisable. Thus, the findings of the CellFreeImplant project may lead to fundamental improvements for patients’ well-being and life expectation by the use of cell-repellent or thromboresistent surfaces in a broad range of medical implant devices.
The three main results of the CellFreeImplant project were:
1. Ti-based casings of miniaturized cylindrical implants can be ultrafast-laser processed and anodized to form cell-repellent micro/nano-structures in a ring on their surface. Comparable rings on Ti-cylinders of same composition cannot be overgrown by cells in in-vitro tests in cell culture.
2. Areas which repel cells can be formed on pre-anodized bone plates from commercial production by ultrafast-laser processing.
3. Areas which repel cells can be formed on polymer samples for orthotic prostheses by ultrafast-laser processing.
The possibility of ingrowth of the implanted medical devices, which may complicate their removal after several months or years, for instance for replacement of the battery, restricts the use of these modern implant currently. If this problem could be convincingly solved, application to much more patients would be advisable. Thus, the findings of the CellFreeImplant project may lead to fundamental improvements for patients’ well-being and life expectation by the use of cell-repellent or thromboresistent surfaces in a broad range of medical implant devices.