Nerve autografting is the “gold standard” technique to repair nerve defects with a gap larger than 30 mm. The current commercially available FDA and CE approved nerve conduits offer considerable benefits to the patients suffering from completely transected nerve. They fail, however, to support neural regeneration in gaps over 30 mm. The aim of this research was to design, develop and evaluate new nerve conduits made from a biodegradable nanocomposite material known as polyhedral oligomeric silsesquioxanes incorporated poly (caprolactone) urea/ urethane (POSS-PCL). This material has been previously shown to have favourable cellular interactions. The biomechanical properties of POSS-PCL nanocomposite with varying POSS concentration were evaluated. Increasing POSS concentration resulted in less viscous polymer solution while increased the surface hydrophobicity, surface roughness and in vitro protein absorption. This increase, however, caused a considerable reduction in Schwann cells proliferation and rounded morphology. To enhance cellular interactions of the POSS-PCL surface, it was functionalized with synthetic RGD peptide, which resulted in an increase of SCs average process length while reducing the hydrophobicity of POSS-PCL surface. Furthermore, human adipose derived stem cells were successfully differentiated into Schwann-like cells as determined by S-100 expression and NGF production. The porogen concentration used for making porous conduits was also investigated using solvent evaporation technique combined with porogen leaching. It was demonstrated that 2% POSS-PCL with 30% porogen had the favourable viscoelastic properties for nerve conduit manufacturing. Two types of nerve conduit with varying wall thicknesses were fabricated and examined for their physiochemical properties. Double layered conduits were considered more suitable for the short-term pilot in vivo study as they had higher compressive resistance and suture retention ability than the single layered ones. Following in vivo implantation of conduits, Visual observations showed good interaction of conduits with surrounding tissue and no obvious inflammation at the repair site after 6 weeks. Histology revealed that the porous conduit (17.53±6.44 μm pore size) improved myelin sheath formation compared to non-porous POSS-PCL nerve conduit. Further investigations of POSS-PCL conduits are required to determine if this implant can overcome the limitation of commercially available nerve conduits.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:654613 |
| Date | January 2015 |
| Creators | Sedaghati, T. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1465974/ |
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