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Title: Development of scaffolds incorporating zonal complexity for articular cartilage tissue engineering
Author: Steele, Joseph Allan McKinnon
ISNI:       0000 0004 6422 6789
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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Articular cartilage is an anisotropic tissue composed of compositional and functional layers. One clinical approach to the regeneration of articular cartilage defects incorporates a porous polymer scaffold to support and direct cartilage formation in full‐thickness defects. These scaffolds are regularly isotropic in structure, unlike the tissue they aim to regenerate. A number of scaffold production techniques were combined to produce porous anisotropic scaffolds with zonally‐biomimetic microarchitecture and mechanical properties. The final scaffold design featured a combination of an electrospun fibrous superficial zone, isotropic foam intermediate zone and directionally frozen deep zone. The zonal scaffold microenvironments influenced cellular distribution, gene expression, and extracellular matrix deposition in vitro without requiring chemical modification or culture under dynamic loading. The scaffold development work culminated in a porcine in vivo study, currently on‐going. Initial data from the 3‐month preliminary surgical trial suggests full cellular infiltration of acellular scaffolds, no immunological response, and improved articular surface morphologies relative to empty defect controls. Variations on the polymer poly(ϵ‐caprolactone) (PCL) were investigated for use in osteochondral tissue engineering applications. The incorporation of alternate monomers was found to modify the biological and mechanical properties of the resulting materials and scaffolds. The work contained within this thesis has expanded the field of anisotropic scaffold design, with implications for articular cartilage engineering. The combination of electrospun fibres and anisotropic foams for scaffold engineering was the first in the field when published. The design of the third‐generation scaffold is new to the field, as is the order‐of‐magnitude increase in stiffness in a porous polymer scaffold while maintaining interconnectivity and polymer composition. The observation of differentially aligned ECM within a single multi‐layer scaffold without zonally distinct materials or surface functionalisation is also believed to be the first in the field.
Supervisor: Stevens, Molly ; Dunlop, Iain Sponsor: Natural Sciences and Engineering Research Council of Canada ; Rosetrees Trust ; Wellcome Trust ; Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral