Development of scaffolds incorporating zonal complexity for articular cartilage tissue engineering
File(s)
Author(s)
Steele, Joseph Allan McKinnon
Type
Thesis
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.
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.
Version
Open Access
Date Issued
2015-10
Date Awarded
2016-03
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Stevens, Molly
Dunlop, Iain
Sponsor
Natural Sciences and Engineering Research Council of Canada
Rosetrees Trust
Wellcome Trust (London, England)
Engineering and Physical Sciences Research Council
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)