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Title: Deformation and fracture of soft materials for cartilage tissue engineering
Author: Butcher, Annabel Louise
ISNI:       0000 0004 7426 4367
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2018
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Damaged cartilage can cause severe pain and restricted mobility, with few long term treatments available. The developing field of tissue engineering offers an alternative to the currently used full joint replacement. Restoring damaged cartilage through tissue engineering would enable an active lifestyle to be recovered and retained, without restrictions to joint mobility. This is increasingly important as the prevalence of osteoarthritis rises. Tissue engineering requires biomaterial scaffolds that mimic the function of the tissue while cells develop, and so the scaffold must provide the appropriate biological, chemical and mechanical stimuli. In this work, methods were developed to enable the design of scaffolds that mimic the microstructure and mechanical properties of articular cartilage. Electrospinning was investigated as a method to mimic the nanoscale collagen fibres within cartilage extracellular matrix. A parametric study was conducted to determine how changes to a gelatin solution affect the mechanical properties of the non-woven fibrous mesh. The solution properties had a clear impact on the morphology of the fibres, but the effect on the mesh mechanical properties was convoluted. The results demonstrated the need for greater understanding of the 3D morphology of electrospun meshes, to establish how these may be altered in order to design scaffolds with desirable mechanical properties. The fracture mechanics of soft materials are complex, and are generally overlooked when designing tissue engineering scaffolds. The complexities have led to a lack of standardised testing, making comparisons between studies impractical. In this work, fracture testing methods were compared, using a viscoelastic polymer to mimic some of the complexities of soft tissue mechanics. Mode III trouser tear tests and mode I pure shear tests were found to provide reliable measurements. Due to the ease of testing small samples, trouser tear testing was concluded to be the most advantageous for determining the fracture resistance of soft tissue engineering scaffolds. Finally, electrospun meshes were combined with hydrogels to create biomimetic scaffolds, which were characterised using tensile and trouser tear fracture tests. Fibre-reinforcement was shown to enhance the mechanical properties of a weak hydrogel, but diminished those of a strong, tough polyacrylamide (PAAm)-alginate hydrogel. The PAAm-alginate hydrogel exhibited mechanical properties close to those of natural articular cartilage, but without the microstructure that would enhance its suitability for use as a cartilage tissue engineering scaffold. An alternative method for reinforcing PAAm-alginate was proposed, which shows promise for producing a biocompatible scaffold that mimics both the mechanics and the microstructure of articular cartilage. Ultimately, this thesis aimed to improve the design of biomimetic scaffolds for cartilage tissue engineering, and advance mechanical characterisation techniques within this field.
Supervisor: Oyen, Michelle Lynn Sponsor: Engineering and Physical Sciences Research Council (EPSRC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Electrospinning ; Fracture mechanics ; Fibre-reinforced composites ; Hydrogels ; Cartilage tissue engineering