Syed, O; (2015) The Development of a Hybrid Scaffold for Use in Oesophageal Tissue Engineering. Doctoral thesis , UCL (University College London).

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Abstract

The oesophagus as an organ can be affected by a number of medical conditions which may necessitate the need for extensive treatment to correct. One potential approach is to tissue engineer a suitable biomaterial-based replacement for oesophageal tissue. Small intestine submucosa (SIS) is one of a number of naturally-derived extracellular matrix (ECM) biomaterials currently in clinical use; however one of their key limitations is poor mechanical properties. In this work it was found that SIS can be consistently and reliably processed into tubular scaffolds which impart certain potential advantages. The decellularisation of tubular SIS was carried out using four different protocols. One protocol emerged as the most suitable by the criteria mentioned, a perfusion-based method using sodium deoxycholate. Electrospinning was used produce to polymers PLGA nanofibres which mechanically reinforced the tubular SIS. It was hypothesised that this would improve the ECM material’s mechanical properties. Attachment remained an issue between the two layers but this was overcome by altering the shape of the SIS. The SIS-PLGA scaffold was produced with varying fibre alignment, a factor shown to have some influence in vitro and in vivo. The drug delivery potential of the fibres was also considered and the scaffolds had VEGF added to them. Evaluation was by physical testing, in vitro analysis and in vivo implantation. The PLGA scaffold were found to perform well both mechanically and in terms of biocompatibility. They also performed well in vivo with a limited foreign body reaction. The highly aligned fibres (5000 rpm) group was chosen as the best in terms of its all-round properties including good cellular infiltration. The electrospun fibres remained intact at 4 weeks which indicates a potential lasting support role, which was intended. The result of the VEGF incorporation was that there was an increase in the blood vessel density of the tissue surrounding the scaffolds highlighting the benefits of adding growth factors to the scaffold. Overall, it was concluded that the hybrid scaffold have potential for use in oesophageal tissue engineering.

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