The present study has developed poly ε-caprolactone (PCL)/ poly lactic acid (PLA) films with specific internal structure suitable to prepare nerve guide conduit for peripheral nerve repair. The film preparation method has been carried out using an environmental chamber to prepare the solvent cast films with the specific surface structure. Different cellular behaviour of neuronal cell cultures was seen on the pitted films with different pits configurations (size and distribution). The consistent surface morphology provided a reliable surface structure for further in vitro and in vivo studies. The effect of a medical grade sterilisation process using gamma radiation at eight doses (0-45kGy) on PCL/PLA films was explored. It has been shown that material properties, including mechanical strength, were significantly affected, while cellular behaviour and responses (NG108-15) were improved. Grooved films with three groove shapes (Sloped, Square, and V shape) were prepared using patterned silicon substrates, photolithography and wet/dry etching. The groove patterns were successfully transferred and good mechanical strength was observed for grooved PCL/ PLA. Oriented growth of NG108-15 cells was observed on the patterned films with an improved alignment and organisation on SL and V shape grooved films. UV-ozone treatment was used to increase hydrophilicity of PCL/PLA films to improve Schwann cells behaviour. No negative effect was observed on cell growth and proliferation on the treated films however the mechanical properties were reduced. Schwann cells expressed typical long spindle-shape morphology with cell-to-cell interaction in longitudinal direction on the treated grooved films. Consistent to in vitro experiment with NG108-15, Schwann cells alignment was also improved on SL and V shape grooves. A three-week in vivo study was carried out to test grooved and non-grooved conduits in a rat sciatic nerve model. The grooved conduits showed better regeneration, with SL-grooved film showing a significant improvement of nerve regeneration. A separate in vivo study evaluated the effect of wall-thickness on nerve regeneration. However, it was shown that the wall thickness had no positive effect, and the conduit with improved mechanical strength adversely affected the nerve regeneration. In conclusion, a nerve guide conduit was developed with the optimised surface structure to support nerve regeneration. The promising in vitro and in vivo studies together with the suitable biomechanical properties and specific surface structure and morphology indicate that the grooved PCL/PLA conduit is a viable treatment for peripheral nerve repair.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:748002 |
| Date | January 2013 |
| Creators | Mobasseri, Seyedeh |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://www.research.manchester.ac.uk/portal/en/theses/design-and-development-of-a-nerve-guide-conduit-with-novel-structural-properties-for-peripheral-nerve-repair(b7e551b7-80c1-4f65-aaef-955a58623be8).html |
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