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Title: Towards the endothelialisation of tissue engineered heart valves : potential of endothelial progenitor cells
Author: Marei, Isra Yousef
ISNI:       0000 0004 9356 6547
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Background: Currently used replacements to treat heart valve disease are associated with drawbacks that limit their function in the long term. These drawbacks have been linked to the inability of such substitutes to remodel in response to the surrounding environment, due to the absence of viable cells in their composition. In situ tissue engineering of heart valves provides a promise to resolve these limitations. One of the potential endogenous cell sources to endothelialise and populate tissue engineering scaffolds is endothelial progenitor cells (EPCs), which have been shown to participate in repair mechanisms. Thus, the aim of this work was to biofunctionalise polycaprolactone (PCL) nanofibrous scaffolds to enhance the adhesion and proliferation of a subset of EPCs that differentiate to blood outgrowth endothelial cells (BOECs). Approach: (i) BOECs and human valve endothelial cells (hVECs) were compared in terms of phenotype and function; (ii) the biocompatibility of BOECs (and hVECs) with PCL was determined; (iii) PCL was biofunctionalised using the BOEC-specific peptide (TPS), through a covalent crosslinking approach and functionality of the material was determined under static conditions as well as dynamic-flow conditions of the aortic valve, (iv) the ability of the biofunctionalised PCL to capture EPCs/BOECs directly from blood mononuclear cells was tested. Conclusion: BOECs characteristics and their compatibility with PCL make them a potential cell source for the endothelialisation of PCL tissue engineering scaffolds. Biofunctionalisation of PCL using TPS peptide enhanced BOECs capture, without inducing cytotoxicity or inflammatory responses. BOECs cultured on the material were able to align and secret endothelial mediators. Under dynamic conditions, BOECs were able to adhere, proliferate and infiltrate through the modified scaffolds. The modified scaffold was able to recruit endothelial cells from blood mononuclear cells under static conditions. These findings are promising, and should be confirmed under flow conditions in a bioreactor and in animal models.
Supervisor: Chester, Adrian H. ; Mitchell, Jane A. Sponsor: Qatar Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral