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Title: Investigation of human mesenchymal stem cell migration in response to synthetic bone graft substitute materials
Author: Ikramova, Dinara
ISNI:       0000 0004 9355 5856
Awarding Body: Queen Mary University of London
Current Institution: Queen Mary, University of London
Date of Award: 2020
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Increased demand in reconstructive orthopaedic surgery and insu cient supply of autografts and allografts have led to the development of a variety of synthetic bone graft substitute (BGS) materials. Bone regeneration within BGSs has been shown to be sensitive to their levels of total porosity, strut porosity and chemistry. The aim of this PhD was to investigate whether this response is due to modulation of stem cell recruitment to the di erent BGS materials. Three materials were investigated, all as 1-2mm porous granules: Actifuse (AF) silicate substituted hydroxyapatite (SiHA), Inductigraft (IG) with similar chemistry and total porosity to AF, but higher strut porosity and ApaPore (AP) with similar porosity to AF, but comprised of stoichiometric hydroxyapatite. The migration of human mesenchymal stem cells (hMSCs) towards these BGS materials was investigated using transwell inserts with permeable membranes and the cells on both seeded and migrated sides of the membrane were quanti ed using a novel confocal microscopy method. The presence of serum proteins altered the ion exchange between AF and culture medium over 24 hours. The presence of cells further altered this ion exchange in both serum free (SFM) and serum containing media (SCM), and cell survival was severely compromised in SFM. However, migration of hMSCs towards AF was not observed in either SFM or SCM. Moreover, the combination of AF granules and ve chemotactic agents, selected for investigation on account of their reported ability to stimulate cell migration response to a concentration gradient of each agent, also failed to produce a chemotactic response in hMSCS. Furthermore, in SCM each isolated agent did not induce chemotaxis in hMSCs. On comparison of AF, IG and AP in the absence of chemotactic factors only AP enhanced migration of hMSCs, whereas IG remotely promoted an increase in cell numbers on membrane seeded sides. Higher levels of proteins were sequestered on AF, IG and AP surfaces in the remote presence of cells than in the acellular condition, with no signi cant variation in protein species distribution. The ndings of this PhD thesis demonstrate that in vitro experimental parameters may contribute to the response of hMSCs to chemotactic agents, that cell migration is sensitive to BGS chemistry and while increasing strut porosity did not enhance hMSC migration, it was found to remotely increase cell proliferation. Thus when not in direct contact, the presence of cells altered BGS interactions with their surrounding environment, in terms of both ion exchange and protein sequestering, while the presence of di erent BGSs remotely altered cell behaviour. A phenomenon which has not been previously demonstrated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available