Periodic Reporting for period 1 - IN2SIGHT (AN IN VIVO BIOENGINEERED CHIP AS A SMART INTRAVITAL MULTIPHOTON IMAGING WINDOW FOR NEW VALIDATION PROTOCOLS OF BIOMATERIALS) Reporting period: 2021-03-01 to 2022-02-28 Summary of the context and overall objectives of the project Routine clinical use of biomaterials must comply with the biocompatibility tests stated by the ISO10993 EU norms that require a wide use of laboratory animals with an excessive economic burden, particularly for SMEs, and with heavy ethical costs for the society. IN2SIGHT wants to renovate the way the tests are made in order to reduce the number of animals used and to increase the statistical reliability of the analyses.The objectives are to:1. develop a new technology, based on non-linear optical microscopy, capable to observe the immune reaction to the implant of a biomaterial for weeks, during the evolution of the possible reaction, without the need to sacrifice the animal;2. formulate a novel statistical approach to analyze the data relative to the immune reaction;3. make the IN2SIGHT technology known among the stakeholders and initiate the process for an update of the norms through contacts with the relevant regulatory bodies in Europe and USA;3. make the society aware of the possibility to reduce the number of animals in the tests and of alternative methods for the biomaterial and drugs testing;4. develop an innovative numerical simulation method for the immune reaction to the implant of a biomaterial based on agent based techniques with the aim to enhance our interpretation of the immune reaction observed experimentally. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The main results of the project in the first 12 months are:1. development of the data management plan;2. development of the regulatory action plan;3. development of the framework for the numerical simulation platform that takes into account the geometry of the device to be implanted;4. design of the chip in terms of: - a micro-structured niche used for the biomaterial hosting and for the observation of the tissue reaction through optical non-linear microscopy;5. test and assessment of the best geometry of the atlas for the optimal pore size for the tissue reconstitution with the atlas;6 design and prototype of an optical setup for the observation in the niche.7. physical characterization of the optical system for non-linear excitation spectroscopy.Part of the above results have been presented to congresses as talks (5 talks of which 2 invited) or posters (7):• SPIE optical metrology 2021, Munich (online), April 2021• Euro BioMAT symposium, May 2021• European Society of Biomechanics congress, ESB, July 2021The project web site is online since M2: www.in2sight.eu Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) The consortium R&D actions has already produced innovative results in the fields of the laser micro-structuring of resins based on silica and Zirconium and the test of their biocompatibility and of their rigidity for long term implants.Moreover, additional improvement beyond the state of the art are in the field of the optical setup for in-vivo imaging. These encompass the micro-fabrication with resins engineered for high index of refraction and low auto-fluorescence.Finally, we are going beyond the state of the art in the formulation of a modular and effective framework for the simulation of the immune reaction in a confined, well defined environment constituted by the micro-structured niche.The economic impact of the project for the first year is primarily in the R&D activities and comes from the integration of the technologies developed in the laser fabrication facilities of the consortium to the level of microfabrication through nano-imprinting lithography. From the societal point of view, our impact can be judged from our effort to communicate (at congresses and workshops in the field of regulatory actions, beyond the field of photonics research) and to disseminate the results of the project. Notably, we have opened a web site for the project, a twitter page that are active since M2 and organize a workshop opened to the stakes holders (May 12, 2022).
