Health and Biomedical Technologies

Neuro-nanotechnology - Fabio Benfenati’s group

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, ACS Nano, 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.
  4. * Graphene-based interfaces for photostimulation of excitable tissues, such as retina (in collaboration with Materials group)
  5. 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
Neuro nanotechnology group fig1
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.
Neuro nanotechnology group fig2
Schematic illustrating the Graphene-based interfaces for photostimulation of excitable tissues.

Biomedical and prosthetics - Tiziano Bandiera’s group

Graphene is a promising material for a number of applications, including the use in biomedical devices and prosthetics. Understanding the biological response to Graphene is therefore crucial to assess its safety and to design biocompatible materials for biomedical applications.

The aim of our research is to explore at the highest detail level the metabolome and the proteome of living organisms exposed to graphene, looking for changes specifically related to biological responses to this material.

We obtained some interesting result by conducting high-resolution LC-MS/MS studies of the effects of the exposure of primary neurons to Graphene (Bramini et al., ACS Nano, 2016). Results showed substantial changes in the lipid composition of neurons treated with graphene oxide, while proteomics revealed a downregulation of proteins involved in calcium metabolism. Graphene oxide disrupts lipid composition, Ca2+ homeostasis and synaptic transmission in primary neurons. A similar experiment is undergoing for astrocytes: untargeted proteomics revealed material-related changes in protein expression. A corresponding metabolomics experiment is ongoing, but preliminary data show a similar trend.

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. Beside our current activities on neurons and astrocytes, we are also characterizing, in collaboration with N&N, the degradation processes induced by gastric juices on Graphene related materials, by identifying putative soluble degradation products.

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 NSYN and N&N);
  • Task 4.5 Impact of graphene and related material on neuronal cells and tissues (in collaboration with NSYN);
Biomedical and prosthetics fig2
Biomedical and prosthetics fig1
High resolution LC-MS/MS instrument used for untargeted metabolomics and proteomics studies
Unsupervised data analysis of untargeted lipidomics: astrocytes show changes in their lipid composition following exposure to two different Graphene related materials.

NanoBioInteraction - Pier Paolo Pompa’s group

The rapid development of graphene-based technology has raised an active discussion about potential safety hazards. A systematic investigation to relate graphene properties to the exposure routes as well as its biotransformation/fate within the exposed organism still lacks and is pivotal for allowing application of graphene in several fields.

Our research activities want to address two main questions:

  1. Study of biopersistence and biotransformation of graphene-related materials (GRMs) in biological matrices that mimic the ingestion route.
  2. Identification of any possible safety, toxicity, and inflammatory issue of digested GRMs at intestinal level.

In this perspective we obtained important results:

  1. Biotransformation: preliminary Raman spectroscopy and mass spectrometry analyses to study possible structural changes of GRMs after incubation in digestive juices.
  2. Intestinal epithelium: no modification of intestinal barrier integrity and functionality and no inflammation after chronic incubation with digested GRMs.

Research activities are conducted in the following research lines:

  1. Assessment of biodegradation and biotransformation of GRMs during the digestion process by Raman spectroscopy (in collaboration with Materials group) and by mass spectrometry (in collaboration with Pharmachemistry).
  2. Studying the long-term fate (intracellular biopersistence) of GRMs.
  3. Exploiting the possible formation of surface defects and/or doping during the digestion process to find new protocols for surface modification/engineering/degradation of GRMs.

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 NSYN and D3-Pharmachemistry).
NanobioInteraction pier paolo pompa group