Improving The Biocompatibility of Vascular Grafts Using a Biomimicry Approach

Abstract

This thesis explores strategies to improve some facets of biocompatibility deficiencies of synthetic vascular grafts using a biomimicry approach by adding PF8, a fibrillin-1 recombinant fragment. PF8 contains RGD, a potent amino acid sequence that strongly binds to endothelial cells (ECs), smooth muscle cells (SMCs) and fibroblasts. Our In vitro assessments showed remarkable EC attachment and proliferation on PF8. PF8 was covalently bound to PTFE after surface activation with plasma immersion ion implantation (PIII) technology. Preserved PF8 favourable interactions with ECs after immobilisation on PTFE was confirmed. PF8 coating also decreased thrombus formation on PIII treated PTFE. We also demonstrated a method to decrease thrombogenicity of PTFE by covering the surface of PIII PTFE with autologous serum. Finally, we explored the possibility of making a biofunctionalised biodegradable graft. We made an electrospun polycaprolactone (PCL) graft with a 2mm diameter with favourable structure and mechanical properties. The PCL graft was biofunctionalised with PF8 binding using PIII technology. PF8 coated PCL and control PCL grafts were implanted as abdominal aorta interposition grafts in a rat model for 3 and 6 weeks (n=4 for each group, total n=16). No aneurysmal degeneration was noted and there was a layer of luminal EC in all grafts. The patency was significantly lower in the control group. After 3 weeks, there was a trend towards decreased intimal hyperplasia in PF8 coated PCL grafts. After 6 weeks, there was a significant reduction in lumen loss in PF8 coated PCL graft compared to the controls. This finding denotes antiproliferative effect of PF8 on SMCs for the first time in vivo. Remarkable affinity to enhance EC cell attachment and proliferation and suppressive effect on intimal hyperplasia combined with its non-thrombotic nature, make PF8 an excellent candidate to improve biocompatibility of new tissue-engineered vascular grafts.