Graphene Flagship Core2

This proposal describes the third stage of the EC-funded part of the Graphene Flagship. It builds upon the results achieved
in the ramp-up phase (2013 - 2016) and the first core project (2016 - 2018), and covers the period April 2018 - March 2020.
The progress of the flagship follows the general plans set out in the Framework Partnership Agreement, and the second core
project represents an additional step towards higher technology and manufacturing readiness levels. The Flagship is built
upon the concept of value chains, one of which is along the axis of materials-components-systems; the ramp-up phase
placed substantial resources on the development of materials production technologies, the first core project moved to
emphasise components, and the second core project will move further towards integrating components in larger systems.
This evolution is manifested, e.g., in the introduction of six market-motivated spearhead projects during the Core 2 project.

The activities of the Work Package "Health and Environment" are aimed to address these three stages, starting from the physicochemical properties and bio-nano interactions when GRM are introduced in biosystems, taking into account the different routes of exposure. Following the results obtained during the ramp-up phase, where we elucidated the mechanisms on how GRMs interact with cells and the first impact on plants and aquatic species, and based on the preliminary data in the Core 1 project, aiming to link GRM physicochemical features and safe-by-design approaches, the objectives of WP4 in Core 2 will focus particularly on long-term effects of GRMs and on how the natural barriers interact with GRMs.
SISSA will use here in vitro systems to investigate neuroglia signalling regulation by GRMs. In vitro and in vivo models of neuroinflammation disease of the CNS such as multiple sclerosis neurodegeneration will be used, to assess the functional impact of GRM exposure on diseased brain and spinal cord.
The work package related to "Biomedical applications" WP5 develops advanced tools for neuroscience research and next-generation medical neural interface devices towards clinical translation in specific disease models: i) retinal (blindness); ii) cortical (epilepsy); iii) deep-structure (Parkinson's); iv) peripheral nervous system (diabetes, rheumatoid arthritis). The specific goals in WP5 will be [operational TRL range also mentioned]:
• Fabrication and technology up-scaling of neural interfaces integrating single functionality (recording, stimulation or therapeutic delivery) and combined multi-functionalities (recording and stimulation of electrical activity; recording and therapeutic delivery) [TRL 2-6].
• Biocompatibility evaluation of the developed technologies and in vitro and in vivo assessment of the device functionality [TRL 5-6]
• Development of therapeutic element as components of the developed medical neurotechnologies and devices [TRL 2-4]
• Exploitation and commercialization of graphene neurotechnologies in neuroscience research [TRL 6-8]
• Identification of most promising medical devices exploring the feasibility of their translation towards clinical applications by interrogating function under model conditions [TRL 6]
WP5 is the newest research programme in the whole of the Flagship. WP5 aims to move forward in Core 2 by consolidating effort around a single, focused technology: Multifunctional in vivo neural interfaces on ultra-soft flexible probes to achieve integration in recording, stimulation and drug delivery capabilities in a single device.
SISSA: Determine the therapeutic efficiency of inhibited synaptic activity in excitatory neurons from graphene and graphene-drug conjugates in the context of epilepsy and anxiety disease (rat) models. Correlations with in vivo electrophysiology of the focal diseased areas.

Start Date 1 Apr 2019

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