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Development of scaffolds incorporating zonal complexity for articular cartilage tissue engineering

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Title: Development of scaffolds incorporating zonal complexity for articular cartilage tissue engineering
Authors: Steele, Joseph Allan McKinnon
Item Type: Thesis or dissertation
Abstract: 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.
Content Version: Open Access
Issue Date: Oct-2015
Date Awarded: Mar-2016
URI: http://hdl.handle.net/10044/1/52781
DOI: https://doi.org/10.25560/52781
Supervisor: Stevens, Molly
Dunlop, Iain
Sponsor/Funder: Natural Sciences and Engineering Research Council of Canada
Rosetrees Trust
Wellcome Trust (London, England)
Engineering and Physical Sciences Research Council
Department: Materials
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Materials PhD theses



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