Periodic Reporting for period 3 - PANBioRA (Personalized And/Or Generalized Integrated Biomaterial Risk Assessment)
Période du rapport: 2021-01-01 au 2021-12-31
PANBioRA provides a comprehensive solution for the time- and cost-effective risk assessment of new biomaterials under health or disease states or a given biomaterial for each patient in a personalized manner. It focused on standardizing the evaluation of biomaterials and opening the venue for pre-implantation, personalized diagnostics for biomaterial based applications.
PANBioRA provides a modular platform to assess risks at different aspects and length scales. This comprises antibody response, cytotoxicity/genotoxicity at cell level, systemic and local effects at tissue and connected tissues (organ-on-a-chip) level. Moreover, physicochemical and biomechanical characterisation as well as predictive modelling at systems level complement the system.
PANBioRA system will, for the first time, predict the patient specific response to a given biomaterial before its implantation. This will minimize side effects and improve health outcomes.
It will also accelerate the process of validation of the biocompatibility of new devices by providing an automated, comprehensive process for the parallel assessment of risks at different scales aiding new biomaterial discovery and commercialisation.
Altogether, PANBioRA will lead to a substantial economic impact due to a reduction of the amount of tests, decrease in healthcare costs due to complications. It will provide the necessary tools for proper risk management related to biomaterials.
PANBioRA provides a modular platform to assess risks at different aspects and length scales. This comprises antibody response, cytotoxicity/genotoxicity at cell level, systemic and local effects at tissue and connected tissues (organ-on-a-chip) level. Moreover, physicochemical and biomechanical characterisation as well as predictive modelling at systems level complement the system.
PANBioRA system will, for the first time, predict the patient specific response to a given biomaterial before its implantation. This will minimize side effects and improve health outcomes.
It will also accelerate the process of validation of the biocompatibility of new devices by providing an automated, comprehensive process for the parallel assessment of risks at different scales aiding new biomaterial discovery and commercialisation.
Altogether, PANBioRA will lead to a substantial economic impact due to a reduction of the amount of tests, decrease in healthcare costs due to complications. It will provide the necessary tools for proper risk management related to biomaterials.
WP1: A new personalised response detection to the biomaterials methodology using Mimotope Variance Analysis (MVA) has been developed and validated with clinical samples from peri-implantitis and diabetic ulcer. A patent is in preparation for the technology.
WP2: 3 immunocompetent on chip organ models were developed using patient macrophages and established under perfusion conditions. Monitoring of the barrier tissue integrity has been achieved by dedicated impedance sensors developed in WP4.
WP3: The process and microfluidic architecture of a fully automated cytotoxicity test was developed, together with microscope and deep learning based image analysis for real time detection of toxicity. An imaging based microfluidic genotoxicity test architecture was developed and is currently considered for patenting.
WP4: A multiparametric electrochemical sensor system was developed, validated and tested under cytotoxicity testing conditions (WP3), with a patent application submitted. An impedance sensor system allowing microscopy imaging was developed and deployed for barrier tissue models (WP2), as well as an automated ELISA on a chip system for the detection of cytokines from organ models and cytotoxicity tests (WP3, WP4) which led to another patent submission.
WP5: An antimicrobial hydrogel which can combat up to 8 consecutive infections was developed as a testing bed for the above technologies, and a patent submitted. A new methodology for mechanical testing of coatings was developed together with in-depth biomechanical characterisation of 3D printed and conventionally produced medical grade materials (silicone and titanium).
WP6: More than 10 different in silico models have been developed for different aspects of biomaterial related risks including microbiota, corrosion, epithelial layer formation/disruption, immune response, toxic effects of degradation products, migration of immune cells etc. These models have also been deployed as web-tools.
WP7: An integrated device, both functional and usability prototype, has been manufactured and demonstrated. The technology integration routes and further expansion possibilities of the instrument from the design perspective were established.
WP8: Oral microbiota analyses were done with patient samples with and without peri-implantitis. Samples were collected from patients with dental implants and diabetic ulcers, for a comprehensive analysis of the reaction to biomaterials at antibody, cell and local tissue level.
WP9: A horizon scanning tool for the early detection of biomaterial related risks (PANBioRA Risk Radar) was developed, validated and deployed. Multicriteria decision making methodologies were used to develop and deploy PANBioRA risk rating system for quantitative comparison and ranking of biomaterials with the techniques developed from WP1-6.
As part of the transversal activities, a value chain analysis and business case definition and exploitation routes were explored. The regulatory and policy framework of the PANBioRA technologies was studied, leading to a set of policy recommendations.
The project was highly successful in terms of dissemination and communication activities, exceeding its set targets. Partners published 44 academic peer reviewed articles in scientific papers, 30 conference proceedings, 3 books and 1 PhD thesis, attended 73 conferences and published 63 non-scientific and non-peer reviewed articles.
WP2: 3 immunocompetent on chip organ models were developed using patient macrophages and established under perfusion conditions. Monitoring of the barrier tissue integrity has been achieved by dedicated impedance sensors developed in WP4.
WP3: The process and microfluidic architecture of a fully automated cytotoxicity test was developed, together with microscope and deep learning based image analysis for real time detection of toxicity. An imaging based microfluidic genotoxicity test architecture was developed and is currently considered for patenting.
WP4: A multiparametric electrochemical sensor system was developed, validated and tested under cytotoxicity testing conditions (WP3), with a patent application submitted. An impedance sensor system allowing microscopy imaging was developed and deployed for barrier tissue models (WP2), as well as an automated ELISA on a chip system for the detection of cytokines from organ models and cytotoxicity tests (WP3, WP4) which led to another patent submission.
WP5: An antimicrobial hydrogel which can combat up to 8 consecutive infections was developed as a testing bed for the above technologies, and a patent submitted. A new methodology for mechanical testing of coatings was developed together with in-depth biomechanical characterisation of 3D printed and conventionally produced medical grade materials (silicone and titanium).
WP6: More than 10 different in silico models have been developed for different aspects of biomaterial related risks including microbiota, corrosion, epithelial layer formation/disruption, immune response, toxic effects of degradation products, migration of immune cells etc. These models have also been deployed as web-tools.
WP7: An integrated device, both functional and usability prototype, has been manufactured and demonstrated. The technology integration routes and further expansion possibilities of the instrument from the design perspective were established.
WP8: Oral microbiota analyses were done with patient samples with and without peri-implantitis. Samples were collected from patients with dental implants and diabetic ulcers, for a comprehensive analysis of the reaction to biomaterials at antibody, cell and local tissue level.
WP9: A horizon scanning tool for the early detection of biomaterial related risks (PANBioRA Risk Radar) was developed, validated and deployed. Multicriteria decision making methodologies were used to develop and deploy PANBioRA risk rating system for quantitative comparison and ranking of biomaterials with the techniques developed from WP1-6.
As part of the transversal activities, a value chain analysis and business case definition and exploitation routes were explored. The regulatory and policy framework of the PANBioRA technologies was studied, leading to a set of policy recommendations.
The project was highly successful in terms of dissemination and communication activities, exceeding its set targets. Partners published 44 academic peer reviewed articles in scientific papers, 30 conference proceedings, 3 books and 1 PhD thesis, attended 73 conferences and published 63 non-scientific and non-peer reviewed articles.
Using biomaterial specific immunoprofiling we determined specific sequences with biomarker potential for several biomaterial-related complications in a biomaterial specific manner. Patient stratification was possible. We have the first synchronised antibody related biomaterial specific immunoprofiling, patient specific microbiota and patient specific macrophage reaction data.
We progressed in developing first multi-organ immunocompetent model system optimised for biomaterial testing; its incorporation with the sensor structures provide a tool which is more informative than the available state of the art. The simulations developed in this project are already made available separately as webtools to the biomaterial community.
We have developed a multicell type cytotoxicity testing protocol supplemented with cytokine read-outs which gives more detailed information about cell type specific responses and is already incorporated into the PANBioRA testing system. A simplified, faster but effective genotoxicity testing system was designed which will make genotoxicity testing more readily available to material labs due to its transferability. This module is also currently being considered for a patent application. A responsive antimicrobial coating only activated in the presence of bacteria was developed and an anti-inflammatory coating that can change macrophage phenotype is under development. A new coating mechanical characterisation protocol is in place and will largely help in the characterisation of novel coatings.
As part of the response to COVID crisis, we developed antiviral coatings which are being considered for patent application and a coating property determination methodology based on machine learning. The incorporated clinical trials of the project enabled us to have synchronised, personalised testing implementation; which we believe will result in several very high impact factor publications.
PANBioRA’s first biomaterial specific risk radar together with the PANBioRA risk rating system will enable objective, quantitative comparison of biomaterials for different applications. We have a functional and usability prototypes for the deployment of the PANBioRA as a R&D and potential IVD instrument. Such a system can cut the costs of medical device development and facilitate the go to market, leading to very large savings for the industry and safer, faster availability of new biomaterial-based therapies for patients. As a device, PANBioRA has a strong commercial potential which will be harnessed by the partners in the form of a spin-off post project end.
We progressed in developing first multi-organ immunocompetent model system optimised for biomaterial testing; its incorporation with the sensor structures provide a tool which is more informative than the available state of the art. The simulations developed in this project are already made available separately as webtools to the biomaterial community.
We have developed a multicell type cytotoxicity testing protocol supplemented with cytokine read-outs which gives more detailed information about cell type specific responses and is already incorporated into the PANBioRA testing system. A simplified, faster but effective genotoxicity testing system was designed which will make genotoxicity testing more readily available to material labs due to its transferability. This module is also currently being considered for a patent application. A responsive antimicrobial coating only activated in the presence of bacteria was developed and an anti-inflammatory coating that can change macrophage phenotype is under development. A new coating mechanical characterisation protocol is in place and will largely help in the characterisation of novel coatings.
As part of the response to COVID crisis, we developed antiviral coatings which are being considered for patent application and a coating property determination methodology based on machine learning. The incorporated clinical trials of the project enabled us to have synchronised, personalised testing implementation; which we believe will result in several very high impact factor publications.
PANBioRA’s first biomaterial specific risk radar together with the PANBioRA risk rating system will enable objective, quantitative comparison of biomaterials for different applications. We have a functional and usability prototypes for the deployment of the PANBioRA as a R&D and potential IVD instrument. Such a system can cut the costs of medical device development and facilitate the go to market, leading to very large savings for the industry and safer, faster availability of new biomaterial-based therapies for patients. As a device, PANBioRA has a strong commercial potential which will be harnessed by the partners in the form of a spin-off post project end.