Design and development of a prosthetic implant for cardiovascular reconstructions
There is a significant worldwide demand for a small calibre vascular graft for use as a bypass or replacement conduit. Our lab has developed a novel nanocomposite polymer based on polyhedral oligomeric silsesquioxane and poly(carbonate-urea)urethane (POSS-PCU) which has displayed promising properties in vitro. In this thesis, POSS-PCU has been utilised to fabricate prosthetic small calibre conduits for use as arterial replacements. An important feature in determining the success of a graft is the wall structure which includes porosity, pore size and pore interconnectivity, which play a crucial role not only in determining the extent of graft healing but also on mechanical behaviour.
A novel extrusion/phase inversion method was investigated and optimised to produce grafts with a range of pore sizes (0-30 μm) and porosities (up to 90%). With mismatches in mechanical properties implicated in the aetiology of intimal hyperplasia, the dynamic mechanical behaviour of grafts was investigated. Grafts could be engineered with compliance values ranging from 5 to 12 per mmHg×10-2 compared to an average value of 5.9 per mmHg×10-2 for the native artery. Biocompatibility is largely dependent on surface properties which were extensively characterised for each of the porous grafts. Grafts were found to readily endothelialise in vitro and were resistant to platelet activation.
An external graft reinforcement method was developed in order to minimise graft kinking. Finally, the grafts were evaluated in vivo in an ovine model following GLP protocols for a period of 9 months.
A patency rate of 70% was achieved (n=10). The positive in vitro results and successful conclusion to the large animal trial suggest that POSS-PCU small calibre grafts are a promising candidate for cardiovascular reconstructions.
Next employment after CoMPLEX:
Post-Doc at the Department of Tissue Regeneration, University of Twente, Netherlands
- Ahmed M, Ghanbari H, Cousins BG, Hamilton G, Seifalian AM,. “Small calibre polyhedral oligomericsilsesquioxane nanocomposite cardiovascular grafts: influence of porosity on the structure,haemocompatibility and mechanical properties” Acta Biomater. 2011 Nov;7(11):3857-67
- Desai M, Ahmed M, Darbyshire A, You Z, Hamilton G, Seifalian AM., “An aortic model for thephysiological assessment of endovascular stent-grafts” Ann Vasc Surg. 2011 May;25(4):530-7
- Ahmed M, Hamilton G, Seifalian AM. “Viscoelastic behaviour of a small calibre vascular graft madefrom a POSS-nanocomposite” Conf Proc IEEE Eng Med Biol Soc. 2010;2010:251-4
- Ahmed M and Seifalian AM, “Organs from Nanomaterials” in Handbook of Nanophysics:Nanomedicine and Nanorobotics, CRC Press, 2010, Chapter 19
- Ahmed M, Yildrimer L, Khademhosseini A, Seifalian A, “Nanostructured Materials forCardiovascular Tissue Engineering” Journal of Nanoscience and Nanotechnology, in press