LAUSR

Biomaterial-based solutions play an increasingly important role in medicine. They can be used in various applications in the healthcare system, e.g. in advanced therapy medicinal products or medical devices including various immunotherapy applications. Our body generally reacts well to these natural or synthetic materials. However, this positive reaction is not universal and complications such as infection, allergies, collateral tissue damage, chronic inflammation or loss of functionality due to immune reactions can occur [1]. Moreover, there are a number of different types of biomaterials (for example different metals and alloys (pure titanium and its alloys for example) are available for dental and orthopaedic implants with different surface coatings (such as Hydroxyapatite coatings) or treatments) that can be applied to the same method of treatment. Although, to determine a median, quantifiable immune response to any given material is possible to attain experimentally, the individual response to the same material generally follows a Gaussian distribution and a material can be completely harmless for one patient and potential dangerous for another [2]. For novel biomaterials especially, this poses a difficulty to quantify risks. Considering all these different options and impending risks it is difficult for physicians to decide which materials are best suited to which patients, primarily because there are no tools currently for assessing patient-specific immune reactions to biomaterial. This lack of suitable and sufficiently wide-ranging methods that would allow a comprehensive risk assessment of using biomaterials hinders the application of the advances of biomaterials in clinic. Since January 2018, 17 partners from 11 European countries are working on a solution to this problem in the frame of the EU-funded project PANBioRA (www.panbiora.eu). The aim is to provide a more intelligent way of selecting the most suitable biomaterial for potential implantable devices. By making personalised, pre-implantation diagnostics possible for the first time, PANBioRA will lead to a significant improvement in the risk assessment of biomaterials which will decrease the complications following implantation procedures. The French Medtech company Protip Medical is the scientific coordinator of the project supported by Steinbeis 2i GmbH as administrative coordinator. The project harnesses diverse expertises ranging from immunology, tissue engineering, electrochemical biosensor, antibody-based sensor systems, mechatronics, microfluidics, clinical research, risk assessment and simulation. By putting together a comprehensive set of technical capacities, we aim to provide new tools to researcher and clinicians in our common goal of providing the best care for the patients with least amount of complications. During the 4-year project a testing system will be developed integrating different technologies into a single instrument that will be able to perform multiple analyses on cell (including autologous macrophages) and microtissue levels (where the tissues are made immunocompetent by the inclusion of relevant immune cells for mimicking resident immune cells) . Beyond the different testing modules, the PANBioRA system includes simulations and multiscale models of cell/tissue biomaterial interactions as well as a risk radar tool. The PANBioRA testing model combines new technologies in the evaluation of biomaterials together with refining and miniaturising conventional techniques. With its multidisciplinary protocols and procedures, a new standard for the evaluation of biomaterials will be set and biomaterial risk assessment at nano-, microand miliscale ranges will be made possible (Fig. 1). For tests at nanoscale level, an innovative immunoprofiling method, the Mimotope Variation Analysis (MVA) based antibody testing is being used (Protobios, Estonia). This method detects the recognition of a specific biomaterial by the immune system in a personalised manner which allows determining patient-specific antibody response profiles for new or existing biomaterials. The MVA is a propriety technology of the Estonian SME and project partner Protobios. During the first year of the project first clinical samples, collected by the clinical project partner Centre Hospitalier Universitaire de Liège (Belgium) are being tested with the MVA in order to validate the methods’ efficiency. Samples of patients suffering from periimplantitis (for validation of the personalised mode of the system) and diabetic ulcers (for testing coatings) are being collected since the obtention of the necessary authorisations. The validation of the testing system with actual patient samples will be applied to the whole PANBioRA system during the course of the project. In order to analyse biological information at microscale level, biomaterial and cell testing methods are integrated. Biochemical responses of cells to the presence of biomaterials will be monitored in real time and by integrated biosensors. Real-time electrochemical sensing will be used to determine the cellular response to a given biomaterial. A set of proand anti-inflammatory cytokines released to the extracellular environment will be used as biomarkers to assess the cell response to different biomaterials. The French research institution Commissariat à l’énergie atomique et aux énergies alternatives (CEA) actively worked on the