Design and development of novel "off the shelf" small diameter helical electrospun graft

Parikh, Vijay (2016) Design and development of novel "off the shelf" small diameter helical electrospun graft. PhD thesis, University of Bolton.

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There is an acute clinical need for small-calibre (<6 mm) vascular grafts for surgery, but unlike their large counterparts they still fail in long-term clinical application. The failures of small diameter grafts are primarily due to the early formation of thrombosis and intimal hyperplasia. Dynamics of blood flow leading to wall shear rate and blood flow pattern and their effect on the endothelial cell proliferation along with other anomalies, have been identified as one of the major deciding factors for the efficiency of grafts. Research has showed that intimal hyperplasia and associated complications which leads to the failure of graft develop preferentially in regions where there is disturbed blood flow haemodynamics which leads to uneven shear stress and turbulence in the flow, followed by flow stagnancy in the periphery of the graft. On the basis of these findings and the established advantages of swirling physiological blood flow, a new graft design having a swirling flow inducer on the inner surface of the graft throughout the axis has been proposed. Initially, different swirling profiles have been analysed using final elemental analysis and compared with conventional or plain grafts. The numerical analysis has revealed that the proposed design could indeed produce the swirling blood flow with much better haemodynamics. These analyses have shown that compared to plain graft, in swirling graft, blood flow velocity near the vessel walls significantly enhanced with uniform distribution of shear stress and thus could theoretically enhance performance of the grafts by providing a "wash away" effect and prevent the plaque formation. Electrospinning has been used to fabricate the proposed design and prototype samples have been produced using polyvinyl alcohol (PVA) and gelatine. After cross linking, prototype grafts have been tested as per standard protocols and various tests such as; uniaxial tensile tests, bursting strength tests and suture retention test were carried out and results were evaluated and compared with the conventional grafts. Human coronary artery, endothelial cells (HCAEC) and human cardiac myocytes (HCM) were seeded on the helical and plain grafts using surface seeding technique. At various time intervals cell proliferation, viability and morphology were observed in the presence of static and circulating media and results were compared with their conventional counterpart kept under the same conditions. Results obtained showed considerable amount of difference in cell spreading and cell viability in the helical graft as compared to the conventional graft which provided the advantage edge. Also, in the case of helical graft more uniformly in arranged HCAEC were observed with elongated morphology. Pressure myography studies were performed on both grafts and after endothelization, the helical graft proved to be more reliable and capable of withstanding the pressure as compared to conventional counterparts. It is therefore suggested, that the electrospun helical graft designed and fabricated in this work may be an attractive candidate for use as a potential small diameter vascular graft for implantation. This is based on its ability to better regulate haemodynamics of blood flow and support endothelization, albeit in vivo studies are required to fully substantiate the in vitro results.

Item Type: Thesis (PhD)
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Health and Wellbeing
School of Engineering > Biomedical and Medical Engineering
School of Sport and Biological Sciences > Medical Biology
University of Bolton Theses > Biomedical and Medical Engineering
Depositing User: Sarah Taylor
Date Deposited: 05 Sep 2016 12:23
Last Modified: 04 Apr 2019 14:31

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