Health and Biomedical Technologies

Neuro-nanotechnology - Fabio Benfenati

Graphene is bound to become the material of choice for engineering environmentally friendly devices including neuroprostheses. However, the small size and unique properties of graphene pose potential risks to human health. Nanosafety is crucial to translate any future development of graphene into action, especially for bio-medical applications.

 
 

Our research activities want to address the following questions:

  1. Is the use of graphene safe? In particular, what are its effects on the nervous system, blood-brain barrier and renal barrier?
  2. In case of toxic effects, what are the mechanisms involved?
  3. Can graphene be used to develop new generation medical implants integrating recording and stimulation functionalities (photo-stimulating devices)?

What we obtained are important results for understanding the behaviour of graphene with biological systems. In particular, we underlined:

  1. Graphene oxide nanosheets disrupt lipid composition, Ca2+ homeostasis, and synaptic transmission in primary cortical neurons (Bramini et al, 2016).
  2. Graphene oxide nanosheets alter astrocyte morphology, Ca2+ dynamics and K+ physiology (Chiacchiaretta, Bramini et al, in preparation).
  3. Graphene flake exposure does not disrupt blood-brain barrier function, with minimal leakage across the endothelium layer.
  4. Graphene inks and CVD graphene support the growth of healthy neuronal networks, and can be therefore considered biocompatible materials. These devices will be tested for modulating neural activity under light stimulation.

Research activities are conducted in the following research lines:

  1. Toxicity of graphene nanosheets in vitro in neural cells, and in vivo in rodents (in collaboration with Pharmachemistry group).
  2. * Conductive graphene-based 2D/3D scaffolds for neuronal cells to drive neuronal regeneration (in collaboration with Materials group).
  3. Effects of graphene-related materials on the physiology of blood-brain and renal barriers.
  • * Graphene-based interfaces for photostimulation of excitable tissues, such as retina (in collaboration with Materials group)
  • Metabolomic studies and identification of biomarkers for graphene toxicity (in collaboration with Pharmachemistry group)

* with IIT Graphene Labs

Connection with Graphene Flagship project

WP4 – Health and Environment

  • Task 4.3 Impact of GRMs in vitro on lung, skin, gastric and renal barriers (in collaboration with D3-Pharmachemistry and N&N);
  • Task 4.5 Impact of graphene and related material on neuronal cells and tissues (in collaboration with Pharmachemistry group);
  • Task 4.6 Exploiting the conductive properties of graphene in 2D neuronal interfaces and studying the physiology of neuronal cells and biological barriers challenged with GRMs

WP5 – Biomedical Technologies

  • Task 5.5 Technologies for electrical stimulating devices
  • Task 5.7 In vitro functional characterization of retinal, cortical, deep-structure CNS, and PNS devices
Scanning Electron Microscopy (a, b, c) and Fluorescence Confocal (d, e, f) images of primary neurons: (i) exposed to graphene nanosheets, (ii) grown onto CVD graphene substrates and (iii) 3D scaffolds.

 Schematic illustrating the Graphene-based interfaces for photostimulation of excitable tissues.

 

 

Bioanalysis and OMICS - Andrea Armirotti

The aim of our research is to explore at the highest analytical detail the chemical space (metabolome and proteome) of living organisms exposed to Graphene, investigating changes associated to the biological responses to this material. We obtained interesting results on the effects of the exposure of primary neurons (Bramini et al, 2016) and astrocytes (Bramini et al. 2019) to Graphene. Our results show substantial changes in the lipid and protein composition of these cells. Particularly interesting is the dysregulation of calcium metabolism we observed. Our role in the Flagship is to conduct omics research activities by means of high-resolution mass spectrometry, in close collaboration with other groups (NSYN mostly). Our expertise in this field is generating useful data for a better understanding of the biological response to Graphene. We are also currently exploring new analytical protocols to investigate the orientation of corona proteins of Graphene nanomaterials, also in view of their in-vivo applications. The Lab is now launching a new MALDI-Imaging based workflow, with the aim to expand the analytical options available for the Flagship. This techinque also proved to be a important option to directly detect graphene oxide in biological tissues, without the need of radiolabeling (Cazier et al. 2020)..