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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - PANBioRA (Personalized And/Or Generalized Integrated Biomaterial Risk Assessment)

Teaser

Summary

PANBioRA aims at providing 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 will standardize the evaluation of biomaterials and open the venue for pre-implantation, personalized diagnostics for biomaterial based applications.
PANBioRA will provide 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 will complement the system. This will be achieved by connecting testing modules in a structure supported by web-based modelling and risk radar tools together with a biomechanical testing system.
The platform will incorporate standardized protocols yielding significantly more information than the current methods for biomaterial risk assessment. Its accuracy will be demonstrated using known reference materials and validated in a pre-clinical setting.
PANBioRA will for the first time, predict the patient specific response to a given biomaterial before its implantation. This measure will allow for the selection of the best suitable material, minimizing side effects and improving 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 proper risk management related to biomaterials.

Work performed

Until M18, different components of PANBioRA were designed and developed. We developed a new immunoprofiling method for biomaterials with mimotope variation analysis. We are already testing clinical samples. 3 organs on a chip models (respiratory, gut and liver) have been developed and tested. The models are ready to be connected and for tests with biomaterials. The design and specifications of an automated cytotoxicity module were done. Cytotoxicity tests were carried out for the image analysis-based algorithm development. Algorithms were developed for the assessment of cell response to biomaterials and they were improved using machine learning and deep learning. A mini-microscope system was designed for integration to the PANBioRA. In order to enrich the amount of information in cytotoxicity tests, electrochemical sensors for pH, H2O2, Lactate and NO have been developed and the optimal sensors were put together in a multiparametric format. A microfluidic cytoxicity cartridge comprising the sensor was developed (ready to be integrated). The target cytokines for antibody-based biosensors were determined and an automated, light activated chip was developed which is also ready for integration. A new antimicrobial coating was developed as a test bed and was used for the validation of PANBioRA components. The biomechanical comparison of 3D printed and conventional biomaterials was carried out which revealed significant differences. In silico models to supplement the testing systems were developed together with models that can simulate conditions which are beyond the capacity of the experimental parts (such as monocyte behavior in bioreactors, hepatocyte aggregation and response of the hepatocyte spheroids to toxins, corrosion of metals, and epithelial cell/microbiota interactions in the presence of biomaterials). A voice of the customer survey was carried out. The detection of the pain points together with the inputs from the partners resulted in the first designs of the system which currently guides the first integrated prototype development. The authorization for the collection of clinical samples was obtained and the sample collection and delivery were underway. A stakeholder survey was developed and carried out for the development of PANBioRA risk radar. Overall, several innovative components of the PANBioRA integrated biomaterial testing system have been designed, developed and tested.

Final results

The immunoprofiling for biomaterials using MVA has never done before and it provided us with insights that are not possible by other methodologies. Our aim is to have a fully developed testing kit for biomaterials by the end of the project. The testing protocol developed has potential for a patent application. Organ-on-a-chip models developed had a certain level of immunocompetency and with the added support from the simulations developed; they have the capacity to provide more information than the available on-chip systems. Current on-chip models are more disease oriented and there is no specific module for biomaterial testing. By the end of the project we aim to have a connected 3 organs-on-a-chip module which can be monitored by electrochemical and antibody-based sensors. The simulation supplemented organ-on-a-chip development both in the maturation and additional data creation is a new approach and with the proof of concept provided in PANBioRA can be adapted to different scenarios. The cytotoxicity module with multiparametric electrochemical sensor chambers and image analysis-based cytotoxicity testing does not exist in the literature. By the end of the project, we aim to offer this system as a kit. This module has also high IP potential. Incorporation of multiparametric electrochemical sensors and automatized cytokine detection enriches biomaterial assessment and testing in a way beyond the SOA. The cytokine detection chip developed resulted in a patent application. A novel antimicrobial coating which can defend medical devices up to 7 subsequent infections also resulted in a patent application. We use this coating as the first demonstration of the PANBioRA testing for showing the benefits of our approach and valorizing it by a new start-up that span out of the project (SPARTHA). The biomechanical findings about the differences between 3D printed/ molded implants are currently used as a basis of new personalized implant. Currently there are no integrated biomaterial testing device that can quantify the cellular response to new biomaterials; thus, the PANBioRA instrument is unique in this aspect and once demonstrated to be effective and user friendly can become a household item in biomaterial laboratories and then in hospitals. The clinical sample collection carried out in the project will be used for the initial validation of the potential of the system. By the end of the project we aim to have a complete set of data on clinical samples. There are no Horizon Scanning tools, as foreseen in the case of PANBioRA Risk Radar, dedicated to biomaterials and we aim to provide such a tool to the biomaterials community. The scientific output was 13 article publications and 1 book publication in the period. 2 patent applications were made. We aim to have 80 scientific publications by the end of the project and 8 patent applications and potentially a new PANBioRA start-up for valorization of the project results. The project output will provide new tools and a better understanding of biomaterial/cell interactions which will have significant technical impact.