Tendon damage, both traumatic and degenerative, results in extensive morbidity in man and also in animals, such as racehorses. This is due to the inferior quality of scar tissue produced in response to tendon damage, which is biomechanically and biochemically weaker than the original tissue. This research has investigated the fabrication of a temporary tendon scaffold for surgical implantation into damaged tendons to facilitate superior repair. Tendons are a highly fibrous tissue, which has necessitated the production of a scaffold capable of recreating this complex hierarchical structure. The potential for electrospinning to produce fibres with dimensions similar to the extracellular matrix of natural tissues has led to its utilisation for the purpose of creating a tendon scaffold. Polycaprolactone was the selected material for scaffold composition due to its bioresorbability over long time periods coupled with its low toxicity in vivo and FDA approval. To establish the optimum parameters for producing fibres of appropriate dimensions, investigations focused on the use of different solvents, polymer molecular weight and parameters of the electrospinning process. The studies concluded that acetone and high molecular weight polymer (80,000 Mn) at a concentration of 10 % w/v was the optimal polymer/solvent solution. Fibres with diameters <1 urn were produced with the following electrospinning parameters; flow rate 0.05 mllmin, voltage 20 kV and needle-tip to collector distance> 10 cm. Fibre production was controlled using different collector methods. Random networks were collected on stationary plates, whilst aligned fibres were collected on mandrels rotating at an optimised speed. In order to mimic the hierarchical bundle structure observed within the Achilles tendon, 3D bundles of electrospun fibres were developed from four different techniques, each of which was associated with advantages and disadvantages. 3D bundles formed by collection from the edge (3 mm) of a fine rotating mandrel (500 RPM) were selected for all further investigations due to their uniformity and reproducibility, although these demonstrated slightly lower mechanical properties compared to two other bundle fabrication techniques. The mechanical properties of 3D bundles were significantly superior compared to 2D aligned fibrous mats. Biodegradation studies showed that 3D bundles degrade at a lesser rate compared to PCL solvent cast films. Bundles were biocompatible with tenocytes over a two-week in vitro study. Cells demonstrated interaction, proliferation and synthesis of extracellular matrix containing collagen. A pilot in vivo study - whereby the 3D bundle was surgically implanted into the Achilles of a murine model - assessed the efficacy of the scaffold over a three-week period. Mice returned to normal ambulation within 48 hrs and all mice survived until harvest. At three weeks the bundle was observed to be fully integrated into the tendon with visible new tissue formation. It is envisaged that with further development this may lead to production of an off-the-shelf scaffold appropriate for clinical application.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:512197 |
| Date | January 2009 |
| Creators | Bosworth, Lucy A. |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://www.manchester.ac.uk/escholar/uk-ac-man-scw:98095 |
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