Development of an improved two-stage seeding process for a nanocomposite vascular graft using human peripheral-blood derived endothelial cells
Background: Currently available prosthetic small calibre vascular grafts have poor medium and long term outcomes due to the development of neo-intimal hyperplasia caused by their non-compliant properties and lack of an endothelial cell lining. Here a nanocomposite based on polyhedral oligomeric sils...
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University College London (University of London)
2017
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| Online Access: | https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.724626 |
| Summary: | Background: Currently available prosthetic small calibre vascular grafts have poor medium and long term outcomes due to the development of neo-intimal hyperplasia caused by their non-compliant properties and lack of an endothelial cell lining. Here a nanocomposite based on polyhedral oligomeric silsesquioxane (POSS) attached by direct reaction onto a urethane segment was employed as a potential vascular graft material. It has been demonstrated to have similar viscoelastic properties to a native artery and be resistant to degradation. Initially Human Umbilical Vein Endothelial Cells (HUVEC) were employed as the cell source of choice after which investigations were carried out into the suitability of human peripheral blood derived circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) for graft seeding. Aim: The aim of this study was to develop a system with the potential to deliver an EPC/CEC-seeded bypass graft in a realistic time-frame. Methods: The cytocompatibility of the nanocomposite was initially investigated using HUVEC as a cell source. Surface modification of the nanocomposite to improve cell adhesion and proliferation was then attempted using UV exposure. Seeded nanocomposite grafts were then exposed to flow and the effect of preconditioning investigated. Following this the use of human peripheral blood derived EPC and CEC as a potential cell seeding source was investigated. Studies were also carried out into the sterilization of the nanocomposite. Results: The nanocomposite was able to support the attachment and growth of both HUVEC and EPC/CEC. Nanocomposite grafts were successfully seeded and exposed to flow with cells being retained on the graft surface following exposure to flow. Conclusions: The results obtained suggest that the nanocomposite graft and the use of EPC/CEC derived from human peripheral blood process has potential both for a realistic and achievable two-stage seeding process for vascular bypass grafts. |
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