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Title: Development of a chitosan scaffold system supporting spatially resolved mesenchymal stem cell differention for osteochondral tissue repair
Author: France, Louise Amy
ISNI:       0000 0004 2725 1803
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2011
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Damage to cartilage such as osteochondral defects affect a large number of people worldwide, severely reducing the patient's quality of life due to extensive pain. This also has adverse affects on healthcare systems with an increasing demand for revision surgery due to the failure of current systems. One of the challenges associated with tissue engineering an osteochondral graft, is that of being able to produce a construct that houses a bone-like and cartilage-region. Often this is done by producing two separate scaffolds and then combining them once the two tissues have been established. This often leads to delamination when under physiological loading; the main cause of failure after implantation. The hypothesis of this thesis was that a scaffold made from a single material that could be tailored to house a cartilage-like region and a bone-like region would overcome the problem of delamination. The use of a single cell source that could undergo osteogenic and chondrogenic differentiation would also benefit the system. This hypothesis was examined using a novel method to produce chitosan scaffolds (85 % porous) that contained a region of small pores (180-300 IJm) and a region of large pores (300-425 IJm) tailored to aid chondrogenic and osteogenic differentiation of human mesenchymal stem cells (MSCs), respectively. Studies into the development of a single culture medium that could initiate both osteogenic and chondrogenic differentiation with the aid of the scaffold architecture revealed that the inclusion of foetal calf serum (FCS) for just the first 5 days of culture had no inhibitory effects on chondrogenic differentiation, whilst still being able to promote successful osteogenic differentiation. With the use of a perfusion bioreactor system, it was found that the combination of the devised culture medium and scaffold architecture could direct MSC differentiation to produce a scaffold that contained osteoblast-like cells in the large pore region, and chondrocyte-like cells in the region of the small pores.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available