Electrospun PCL fibres for oesophageal tissue engineering

Johnston, Anna ORCID: 0000-0002-8726-8055 (2024). Electrospun PCL fibres for oesophageal tissue engineering. University of Birmingham. Ph.D.

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Abstract

Tissue engineering and regenerative medicine offer promising solutions for the treatment of oesophageal disorders including cancer treatments and Barrett’s oesophagus, which often require oesophagectomy followed by replacement of the lost tissue. Due to ongoing donor tissue shortages, there is a need for a tissue engineered solution, yet the development of suitable biomaterial scaffolds remains a critical aspect of this field.
This thesis presents the development of an electrospun polycaprolactone material tailored for oesophageal tissue engineering applications, with the novel step of adding microscale topography to the inherent nanoscale topography of an electrospun material.
The optimisation of the electrospinning process prioritised the reduction of the fibre diameter and enhancement of fibre alignment, key factors known to influence cell migration and tissue organisation. Parameters including applied voltage, solvent system, needle tip-collector distance and collector speed were optimised. The optimisation process determined that a 10 % w/v solution in a 50:50 chloroform:dimethylformamide solvent system using a mandrel collector rotating at 2000 RPM produced highly aligned fibres with small diameters and free from beading.
Tensile testing revealed highly anisotropic mechanical properties of the fibre sheets, with an elastic modulus comparable to porcine oesophageal tissue perpendicular to the fibre direction. The fibre sheets exhibited superior strength parallel to fibre orientation, crucial for implantable materials, while maintaining high elasticity, albeit lower than native tissue, prompting considerations for in vivo applications.
In vitro degradation experiments in pH 4 and pH 7 environments were carried out, and various characterisation techniques were used to assess the degradation kinetics over a 12-week period. There was significant degradation at both pH conditions, with a more pronounced and prolonged degradation observed under acidic conditions.
Successful fibronectin functionalisation of the fibres significantly augmented their bioactivity, evidenced by cell viability compared to their non-functionalised counterparts, without affecting fibre diameter or alignment. Moreover, functionalisation increased wettability, potentially increasing bioactivity further.
Various sterilisation and disinfection methods; ethanol, ethylene oxide, UV, and gamma radiation, were assessed for their effects on fibre properties. Ethanol and ethylene oxide treatments negatively impacted fibre topography. Conversely, UV and gamma radiation showed minimal effects on fibre morphology, suggesting their suitability for sterilisation.
Investigations into fibroblast response suggested that aligned fibres had an elongation effect on fibroblasts, and that the addition of microgrooves could amplify this effect, but that fibre alignment was the main influencing factor.
This work contributes to the development of an electrospun PCL material with promising characteristics for use in oesophageal tissue engineering, offering insights into its optimisation, functionalisation, sterilisation and degradation behaviours.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):