Polyhydroxyalkanoates (PHA) are biopolymer molecules that have shown increasing evidence of suitability for use as biomaterials. Many different cell types from a range of species have been shown to adhere and develop on PHA scaffolds, with some preliminary in vivo studies having been performed and showing promising results. Several cell types have shown potential for use in tendon tissue engineering. Primary tendon cells (tenocytes) isolated from a rat Achilles tendon (RaT), human Mesenchymal Stem Cells (hMSCs) and human Embryonic Stem Cells (hESCs) have all been utilised throughout this investigation in many different experimental models. To date, research has focused on scaffold design and manufacture, suitability of the polymer for cell culture, in vitro testing in both static and dynamic environments and a pilot in vivo study. The aims of this study were to find if the PHA molecule Poly (hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) is able to support tendon cell culture, to design a scaffold using the polymer that could replicate tendon in vitro and in vivo, to mechanically stimulate cells seeded in scaffolds to encourage extracellular matrix remodelling into tendon like structures and to monitor the construct when placed in situ in a pilot in vivo model. Results have shown that PHBHHx can support RaT, hMSC and hESC development. Mechanical testing revealed a design with similar properties to those of a rat Achilles tendon. Bioreactor studies have demonstrated how hMSCs, hESCs and rat tenocytes can remodel collagen gels incorporated into the scaffold towards morphologies resembling tendon. Preliminary in vivo studies have found that a PHBHHx and PHBHHx/collagen hybrid scaffold show little immune response when placed in situ. In conclusion, this study has demonstrated the effectiveness of PHBHHx and PHBHHx/collagen hybrid scaffolds for use in tendon tissue engineering, providing scope for future breakthrough products and innovations in both scientific and clinical arenas.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:718468 |
| Date | January 2013 |
| Creators | Lomas, Alexander James |
| Publisher | Keele University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.keele.ac.uk/3572/ |
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