Tesi etd-12152017-202713
Link copiato negli appunti
Tipo di tesi
Perfezionamento
Autore
RANAUDO, ANTONIO
URN
etd-12152017-202713
Titolo
"Potentialities of silk fibroin coatings for improvement of biocompatibility of advanced neural interfaces"
Settore scientifico disciplinare
ING-IND/34
Corso di studi
INGEGNERIA - Biorobotics
Commissione
relatore Prof. MICERA, SILVESTRO
Parole chiave
- biocompatibility
- foreign body response
- intraneural electrodes
- neural engineering
- neural interfaces
- silk fibroin
- thin layers
Data inizio appello
29/06/2018;
Disponibilità
completa
Riassunto analitico
With the aim of restoring loss functions in patients suffering for amputation or diseases, outstanding progresses have been made in the neural engineering field. In the last decades, the need of interfacing prosthesis with neural tissue led to the development of several neural electrodes, able to allow direct control of such prosthesis and restoring sensory feedback. Despite the advances in the efficiency and reliability of such devices, a challenging issue has hindered the possibility of long-term application. In fact, the implantation and chronic presence of a neural interfacing device induces a cascade of biological processes leading to fibrotic capsule formation, which can ultimately isolate the electrode and gradually decrease device performance. The absence of degradation of implanted devices exacerbates immune reaction and, over time, extra layers of non-excitable cells will increase the neural interface impedance. For recording electrodes, this reduces the possibility of recording and localising single unit activity due to a diminished signal-to-noise ratio. In this work, we explored the possibility of using silk fibroin to improve biocompatibility of neural interfaces. Silk fibroin is a fibrous protein extracted from Bombyx mori cocoons. It possesses remarkable physicochemical and mechanical properties, as well as excellent biocompatibility.
We tested the suitability of several manufacturing techniques to produce thin film coatings able to mask neural electrode surface, thus improving their biocompatibility; chosen techniques are drop casting, inkjet printing, SAM-inspired adsorption and electrospinning.
Drop casting technique was used with low concentration protein in the attempt of producing thin films. Several strategies adopted to overcome technique limitations, namely coffee ring effect and subsequent non-homogeneous distribution, have been demonstrated not sufficient; therefore, the process has been modified by combination with phase inversion process. A water vapours-annealing process was also employed, resulting in the development of samples with low thickness, high roughness and high hydrophobicity. In vitro tests showed good results in terms of viability, proliferation and immune response of representative cell model for neural implants.
With the aim of exploiting ink jet printing patterned deposition, several studies were conducted on the possibility of formulating a suitable silk fibroin-based ink. Solution characterisation revealed instability of the protein in water and presence of aggregates; moreover, it was not possible to determine a concentration able to satisfy technique requirements. Attempts of improving solution properties by adding different additives have been unsuccessful.
The possibility of obtaining a SAM-inspired chemically adsorbed layer was investigated; studies conducted on silk fibroin revealed a degraded state of the protein due to extraction process from cocoons. The issue related to the loss of cysteine residues in the degraded protein was solved by means of conjugation of L-cysteine. Samples were produced using thin gold layer as substrates; results of characterisation revealed the effectiveness of the technique in covering the gold layer. Although present, the protein distributed on the surface in a non-homogeneous way, and impedance levels of the samples were not satisfactory in order to match requirements of neural electrodes.
Electrospinning technique was tested for producing non-woven meshes composed of silk fibroin. Preliminary results showed the creation of nanofibres with average diameter of ≈500 nm; moreover, it was possible to obtain fibres with high degree of alignment by using a double ground setup.
We tested the suitability of several manufacturing techniques to produce thin film coatings able to mask neural electrode surface, thus improving their biocompatibility; chosen techniques are drop casting, inkjet printing, SAM-inspired adsorption and electrospinning.
Drop casting technique was used with low concentration protein in the attempt of producing thin films. Several strategies adopted to overcome technique limitations, namely coffee ring effect and subsequent non-homogeneous distribution, have been demonstrated not sufficient; therefore, the process has been modified by combination with phase inversion process. A water vapours-annealing process was also employed, resulting in the development of samples with low thickness, high roughness and high hydrophobicity. In vitro tests showed good results in terms of viability, proliferation and immune response of representative cell model for neural implants.
With the aim of exploiting ink jet printing patterned deposition, several studies were conducted on the possibility of formulating a suitable silk fibroin-based ink. Solution characterisation revealed instability of the protein in water and presence of aggregates; moreover, it was not possible to determine a concentration able to satisfy technique requirements. Attempts of improving solution properties by adding different additives have been unsuccessful.
The possibility of obtaining a SAM-inspired chemically adsorbed layer was investigated; studies conducted on silk fibroin revealed a degraded state of the protein due to extraction process from cocoons. The issue related to the loss of cysteine residues in the degraded protein was solved by means of conjugation of L-cysteine. Samples were produced using thin gold layer as substrates; results of characterisation revealed the effectiveness of the technique in covering the gold layer. Although present, the protein distributed on the surface in a non-homogeneous way, and impedance levels of the samples were not satisfactory in order to match requirements of neural electrodes.
Electrospinning technique was tested for producing non-woven meshes composed of silk fibroin. Preliminary results showed the creation of nanofibres with average diameter of ≈500 nm; moreover, it was possible to obtain fibres with high degree of alignment by using a double ground setup.
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